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EPIDEMIOLOGY—AGING CATEGORY EPIDEMIOLOGY—AGING 1397-P Age of Diagnosis of Type 2 Diabetes Is More Than 9 years Younger in Asian-British Compared With the Rest of the UK Population 1395-P ANDREW J. HARTLAND, JANE DEVILLE-ALMOND, MATTHEW T. ORTON, VICKIE HARTLAND, Walsall, United Kingdom, Liverpool, United Kingdom Does Functional Decline in Older Adults Hasten the Onset of Diabetes? The Health and Retirement Study 1998-2010 Walsall, UK (population approx 175 000) has the second highest prevalence of type 2 diabetes in England and Wales. Observational evidence suggests the age of diagnosis is reducing. This study’s aim was to establish the age distribution at time of diagnosis and quantify the effect of increased pre-disposition for the development of type 2 diabetes amongst AsianBritish. In Walsall, the oral glucose tolerance test (OGTT) remains the main diagnostic test for diabetes. All samples are analyzed at a single Hospital Blood Sciences laboratory. An audit of OGTT requests (excluding ante-natal requests) against the laboratory identification code for OGGT identified 22 735 OGTTs (the majority requested within a 12 month period up to April 2012) of which 3702 were positive, using WHO diagnostic criteria (1929 males, 1773 females) For the total population, mean age at diagnosis = 59.8 years (male), 61.5 years (female). For males: 14.5% were < 45 years and 21.4% < 50 years. Females 14.6% < 45 years and 20.3% < 50 years. Asian-British were identified by demographic information provided. When compared with the rest of the population: BARBARA H. BARDENHEIER, EDWARD GREGG, XIAOHUI ZHUO, YILING J. CHENG, LINDA GEISS, Atlanta, GA Prospective studies have associated diabetes with a high risk of incident disability among older adults. However, the converse association could also occur, with functional decline hastening the onset of diabetes, particularly in those at high risk. 13,134 adults aged over 50 years who entered the longitudinal Health and Retirement Study between 1992 and 2006 with no disability or diabetes were followed to 2010 to determine if those who became disabled would subsequently develop diabetes. Mobility disability was assessed by self-reported difficulty walking one block; walking several blocks; climbing one flight of stairs; stooping, crouching, or kneeling; and pushing or pulling a large object. Participants were classified by disability: none, mild (difficulty with stooping and walking several blocks or difficulty with > 2 mobility measures other than climbing), moderate (difficulty with climbing or difficulty with > 3 mobility measures), and severe (difficulty with > 4 mobility measures). 1,955 (14.9%) participants developed diabetes, 8,228 (62.6%) reported incident disability, and 2,482 (18.9%) died by 2010. Among those who did not develop disability, diabetes incidence was 8.67 per 1,000; among those who developed disability and remained disabled at least 50% of the reporting period, diabetes incidence was 13.5 per 1,000. In a generalized estimating equation controlling for body mass index, age, sex, race/ethnicity, net wealth, and year of report, we found a statistically significant dose-response relationship between incident disability and later incident diabetes: severe vs. none (OR: 2.18, 95%CI: 1.82, 2.61); moderate vs. none (OR: 1.50, 95%CI: 1.25, 1.80); mild vs. none (OR: 1.40, 95%CI: 1.26, 1.56). We found those who become mildly disabled are at increased risk of developing diabetes within a few years. These findings raise the question of whether approaches to delay functional decline, an almost ubiquitous aspect of aging, may reduce the risk of diabetes. 1396-P Genome-Wide Association Study and Linkage Scan Identify Novel Loci Influencing Circulating Glycated Hemoglobin (HbA1c) Levels in Nondiabetics: The Long Life Family Study (LLFS) 1398-P Mother’s Age in Relation to the Haptoglobin Genotype of the Offspring With Type 1 Diabetes PING AN, IVA MILJKOVIC, BHARAT THYAGARAJAN, ALDI KRAJA, WARWICK DAW, JAMES S. PANKOW, ELIZABETH SELVIN, LINDA KAO, NISA M. MARUTHUR, MICHAEL A. NALLS, YONGMEI LIU, TAMARA HARRIS, JOSEPH LEE, INGRID B. BORECKI, KAARE CHRISTENSEN, JOHN H. ECKFELDT, RICHARD MAYEUX, THOMAS T. PERLS, ANNE NEWMAN, MICHAEL A. PROVINCE, St. Louis, MO, Pittsburgh, PA, Minneapolis, MN, Baltimore, MD, Bethesda, MD, Winston-Salem, NC, New York, NY, Odense, Denmark, Boston, MA JESSICA NAN, TREVOR J. ORCHARD, TINA COSTACOU, Pittsburgh, PA Maternal age may influence intrauterine selection and favor specific genotypes compared to others. Recent studies suggested that mother’s age may relate to the haptoglobin (Hp) genotype (Hp 1-1, Hp 1-2, or Hp 2-2) of the offspring with type 1 diabetes (T1D), such that the likelihood of the T1D offspring carrying at least one Hp 2 allele increases with mother’s age. As the Hp 2-2 genotype has further been shown to increase the risk of both cardiovascular disease and kidney function decline in diabetes, evaluating the presence of an association between mother’s age and Hp in T1D is important. We evaluated the hypothesis that maternal age at birth was greater among individuals with T1D and the Hp 2 compared to Hp 1 allele among participants of the Epidemiology of Diabetes Complications study, a prospective study of childhood onset T1D (baseline mean age 28 and duration 19 years). Data on mother’s age and Hp genotype were available for 350 participants. The distribution of the Hp genotype was 12.9% Hp 1-1, 44.9% Hp 2-1, and 42.3% Hp 2-2. Mother’s age was grouped according to previously published categories (≤22 years, 23-36 years, and >36 years). Results are presented in Table 1. Despite a slight suggestion of a trend toward a greater proportion of individuals with Hp 1-1 in the youngest and a lower proportion in the oldest group of mothers, these data do not provide strong evidence for an association between mother’s age and the Hp genotype of the offspring with T1D. Glycated hemoglobin (HbA1c) is a stable index of chronic glycemic status and hyperglycemia associated with progressive development of insulin resistance and frank diabetes. HbA1c is also a glycemic marker that is associated with premature aging and increased mortality. To uncover additional loci influential on circulating HbA1c levels, we conducted a GWAS and linkage scan in 4,088 nondiabetic participants with European ancestry from the Long Life Family Study (LLFS). A total of 11618 nondiabetic participants from 3 other independent cohorts (ARIC Study, Health ABC Study, FamHS) were used to verify the discoveries. HbA1c was adjusted for age, field centers, 20 PCs, w/o BMI, within sex, prior to genetic assessment in the LLFS. Linear mixed effects model assuming additive genetic fixed effects was used for association testing with a kinship model to correct for random effects of familial relationship. Linkage scan was built on haplotypes-based IBD estimation with 0.5 cM average spacing. From GWAS, two known loci at GCK-YKT6 and HK1 were confirmed; two best novel loci were found near OR10R3P and GMPR that were only suggestive. From the linkage scan, two significant linkages (2p22.2 and 2q31.3 with highest LOD of 3.9) and two promising linkages (1q42.2, LOD = 2.30; 7q11.23, LOD = 1.85) were found; all four linkage regions were novel for HbA1c. Our best prioritized common variants under the two significant linkage peaks were identified at/near LOC100130842, QPCT, NEUROD1 and NAB1 (p = 3.6×10-5 to 9.4×10-4) but they were in general nonreplicable in this analysis. Together, our integrative association and linkage approach allowed reconfirmation of two loci at GCKYKT6 and HK1 and identification of two novel linkage regions on 2p22.2 and 2q31.3 that influence circulating HbA1c levels. Future linkage-guided surveys of sequence variants including rare functional and regulatory variants may yield additional findings. Supported by: NIA ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A365 POSTERS In conclusion, more than 1 in 4 diagnoses of type 2 diabetes in AsianBritish is made at age < 45 years and more than 1 in 3 < 50 years The mean age of diagnosis is more than 9 years younger in Asian-British compared to the rest of the population. The UK National Institute for Health and Clinical Excellence in July 2012 published guidelines for the prevention of type 2 diabetes. This study identifies the need for these strategies to be effectively targeted and clinically effective amongst the Asian-British community. Epidemiology/ Genetics Asian-British v Non-Asian-British • Males: mean age of diagnosis 52.9 years v 62.3 years (p<0.01) • % diagnosed< 45 years: 25.6% v 9.2 5% (p<0.001) • % diagnosed < 50 years: 38.4 % v 15.2% (p<0.001) • Females: mean age of diagnosis: 54.5 years v 63.9 years (p<0.01) • % diagnosed < 45 years:: 25.7% v 8.7% (p<0.001) • % diagnosed < 50 years: 35.3% v 15.4% (p<0.001) EPIDEMIOLOGY—CARDIOVASCULAR DISEASE all-cause death) or end of study. The risk of the composite outcome was compared between the 2 treatment regimens using marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, cholesterol, HbA1c, creatinine, blood pressure, BMI, and co-morbidities. Among 199,933 metformin monotherapy users, most patients (N=117,466 [59%]) never added a second drug (mean 43 months of follow-up). There were 1316 and 28274 patients who added insulin or sulfonylureas, respectively. Patients were 95% male and insulin initiators were younger (59 versus 61 years), added treatment earlier (time to add-on therapy 17 versus 22 months) and had higher average baseline HbA1c, (8.5% versus 7.7%) compared with patients who added a sulfonylurea. The CVD or death composite outcome rate was 37.0 versus 19.3 events per 1000 person-years, among insulin versus sulfonylureas initiators respectively (adjusted hazard ratio [aHR] 1.29, 95% CI 0.85, 1.96). CVD event rates were 6.3 and 7.1 per 1000 person-years, respectively (aHR 0.40, 95% CI 0.15, 1.06), while all-cause death rates were 30.6 and 12.2 per 1000 person-years, respectively (aHR 1.77, 95% CI 1.12, 2.79). In preliminary analyses the risk of the composite outcome: CVD or death was similar among those who added insulin or sulfonylurea to metformin. These findings do not explain the observed increased risk of death associated with insulin. Table 1. Distribution of the Hp genotype among offspring with T1D by mother’s age at the time of birth Mother’s age Offspring’s Hp genotype <22 23-36 >36 p-value (n=62) (n=253) (n=35) 1-1 24.4 (11) 71.1 (32) 4.4 (2) 2-1 14.7 (23) 74.5 (117) 10.8 (17) Fisher’s exact 2-2 18.9 (28) 70.3 (104) 10.8 (16) 0.43 Combining those with the 2 allele 1-1 24.4 (11) 71.1 (32) 4.4 (2) p-trend 2-1 / 2-2 16.7 (51) 72.5 (221) 10.8 (33) 0.09 p-trend Proportion of Hp 1 allele 35.8 (181) 36.3 (45) 30.0 (21) 0.46 Supported by: NIH (DK34818) 1399-P 2-Hour Plasma Glucose Increases Much Faster With Age in Abnormal Glucose Tolerant Subjects Than Glucose Tolerant Subjects, While No Difference in Fasting Plasma Glucose Supported by: AHRQ, U.S. Dept. of Veteran Affairs & POSTERS Epidemiology/ Genetics RUDRUIDEE KARNCHANASORN, JEAN HUANG, HORNG-YIH OU, WEI FENG, RAYNALD SAMOA, LEE-MING CHUANG, KEN C. CHIU, Kansas City, KS, Sylmar, CA, Tainan, Taiwan, Duarte, CA, Taipei, Taiwan The prevalence of type 2 diabetes increases with age. Both fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) increase with age. However, there is little information whether the status of glucose tolerance affects the rates of change with age in FPG and 2hPG or not. The subjects with overt diabetes were excluded from the study. Only adult (age ≥ 18 year olds) subjects with normal glucose tolerance (NGT, FPG < 100 mg/dL, 2hPG < 140 mg/dL, and A1c < 5.7%) and abnormal glucose tolerant (AGT, any of FPG 100-199 mg/dL, 2hPG 140-199 mg/dL or A1c 5.7-6.4%) were included in this study with a total of 5,224 participants of the NHANES 20052010. Regression analysis was used to examine the relation of age with FPG and 2hPG. We also considered gender and BMI as covariates. Age was significantly correlated with FPG (r=0.2989, P<0.000001) and 2hPG (r=0.3708, P<0.000001) in non-diabetic subjects. For FPG, significant correlations with age were noted in both NGT (r=0.1235, P<0.000001) and AGT (r=0.0961, P<0.000001) subjects. After adjustment for gender and BMI, the annual rates of change in FPG were similar (P=0.06) between NGT (0.041 mg/dL/year, 95% CI: 0.028-0.054) and AGT (0.062 mg/dL/year, 95% CI: 0.0450.078) subjects. For 2hPG, signification correlations with age were also noted in both NGT (r=0.1884, P<0.000001) and AGT (r=0.2902, P<0.000001) subjects. After adjustment for covariates, the annual rates of change in 2hPG differed significantly (P<0.000001) between NGT (0.229 mg/dL/year, 95% CI: 0.1790.278) and AGT (0.553 mg/dL/year, 95% CI: 0.488-0.619) subjects. After 20 years of aging, FPG increases by 0.82 mg/dL in NGT and 1.24 mg/dL in AGT, while 2hPG increases by 4.58 mg/dL in NGT and 11.06 mg/ dL in AGT. An age specific diagnostic criteria for 2hPG would be required to avoid the unnecessary treatment in the elderly population, in which the ADA recommends a different approach in the management of diabetes. YALI AN, PING ZHANG, JINPING WANG, EDWARD GREGG, BO ZHANG, HUI LI, QIUHONG GONG, YANYAN CHEN, XIAOYAN XING, MICHEAL ENGELGAU, GOJKA ROGLIC, YINGHUA HU, PETER H. BENNETT, GUANGWEI LI, Beijing, China, Atlanta, GA, Daqing, China, Geneva, Switzerland, Phoenix, AZ While stroke is a leading cause of death in China and the numbers of persons with diabetes and impaired glucose tolerance (IGT) are large and growing, the incidence and risk of death attributable to stroke among Chinese adults with these conditions have not previously been quantified. We examined incidence of stroke and related mortality over a 23 year period in a cohort of 630 persons with newly diagnosed diabetes (NDM), 576 with IGT, and 519 with normal glucose tolerance (NGT), who were identified initially in 1986 by screening 50% of the community aged 25 years and over in Da Qing, China. Stroke incidence and related mortality were ascertained up to December 31st, 2009 in some 95% of the cohort. Stroke, fatal or non-fatal, occurred in 218 (36.8%) persons with NDM, 177 (32.7%) with IGT and 121 (24.6%) with NGT. Stroke incidence was higher in men than in women with NDM (29.0 vs. 18.5/1000 person-years) and IGT (22.1 vs. 13.7/1000 person-years), but not with NGT (12.9 vs. 11.4/1000 person-years). The age-adjusted hazard ratios for NDM vs. NGT were 2.15 (95% CI 1.59-2.92) in men and 1.47(95% CI 1.05-2.08) in women. Among those who developed a stroke, death occurred in 145 (66.5%) with NDM, 82 (46.3%) with IGT, and 36 (29.8%) with NGT. Case-fatality rates from stroke (per 1000 person-years) were 130.6 in men and 153.9 in women with NDM, 95.5 and 56.7 in men and women with IGT, and 56.4 and 46.6 in men and women with NGT. Age- and sex- adjusted case-fatality rate ratios were 2.42 (95% CI 1.67-3.69) for NDM vs. NGT and 1.54 (95% CI 1.04-2.29) for IGT vs. NGT. In China, diabetes and IGT lead to considerable excess risk for stroke and excess mortality due to stroke. Persons with diabetes or IGT face double jeopardy by having both a higher stroke incidence and a higher case-fatality rate after a stroke. EPIDEMIOLOGY—CARDIOVASCULAR DISEASE Guided Audio Tour: Cardiovascular Epidemiology (Posters: 1400-P to 1405-P), see page 15. & 1401-P Stroke Incidence and its Long-Term Impact on Mortality in a Population-Based Cohort With Newly Diagnosed Diabetes and Impaired Glucose Tolerance in China: The Da Qing Diabetes Study & 1402-P Metabolic Syndrome in Type 1 Diabetes Patients over 16 years of Follow-Up: The DCCT/EDIC Study 1400-P PATRICIA A. CLEARY, EVRIM B. TURKBEY, JYE-YU C. BACKLUND, JOHN M. LACHIN, JOAO A. LIMA, DAVID A. BLUEMKE, DCCT/EDIC RESEARCH GROUP, Rockville, MD, Bethesda, MD, Baltimore, MD Cardiovascular Outcomes Associated With Insulin versus Sulfonylureas for Diabetes Treatment Intensification CHRISTIANNE ROUMIE, ROBERT GREEVY, CARLOS GRIJALVA, ADRIANA HUNG, XULEI LIU, HARVEY MURFF, TOM ELASY, MARIE GRIFFIN, Nashville, TN Metabolic syndrome (MetS) represents a cluster of cardiovascular risk factors with associated increased cardiovascular risk. We describe the prevalence of MetS in the well-characterized DCCT/EDIC cohort. The Epidemiology of Diabetes Interventions and Complications (EDIC) is the observational study of the Diabetes Control and Complications Trial (DCCT) cohort that received intensive or conventional therapy for 6.5 years. MetS was defined as diabetes plus 2 other abnormalities (elevated waist circumference or triglyceride or blood pressure levels or reduced high density lipoprotein). At EDIC year 1, the prevalence of MetS was 16.5 The optimal medication for add-on diabetes therapy after metformin failure remains uncertain. We compared time to cardiovascular disease (CVD) events or all-cause death among patients who initiated insulin or a sulfonylurea as add-on therapy to metformin. We assembled a national retrospective cohort of veterans who initiated diabetes treatment with metformin between 10/2001 and 9/2008 and then added either insulin or sulfonylurea through 12/2010. Follow-up continued until an outcome (CVD events: AMI or stroke hospitalization; or & For author disclosure information, see page 829. A366 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CARDIOVASCULAR DISEASE % in 1271 subjects (mean age 36 years, 45 % female). The prevalence of MetS increased linearly to 36.8% at year 12 and then stabilized with a prevalence of 36.3% at year 16 (FIGURE). Hypertension and elevated waist circumference increased linearly over 16 years (25.7% and 12.3% at year 1, 65.4% and 36.4% at year 16, respectively). Elevated triglyceride was stable over 10 years (10.5% and 11.5% at year 1 and 10) and then decreased to 8.6 % at year 16 . Older age at year 1, and higher mean HbA1c were associated with MetS (Odds Ratio: 1.28 per 10 years, p<0.0001 and 1.22 per 1%, p< 0.0001, respectively), but not gender or DCCT intensive vs conventional therapy. The prevalence of MetS in T1DM increased during16 years of follow-up without any significant difference by gender or treatment group. Older age and poor glycemic control were predictors of MetS. & 1404-P Intensive Glucose-Lowering Therapy May Reduce Cardiovascular Disease Events in Hispanics in the Veterans Affairs Diabetes Trial (VADT) ARAMESH SAREMI, GIDEON BAHN, LING GE, TOM MORITZ, DAWN C. SCHWENKE, WILLIAM C. DUCKWORTH, NICHOLAS EMANUELE, DOMENIC REDA, RODNEY HAYWARD, PETER D. REAVEN, FOR VADT INVESTIGATORS, Phoenix, AZ, Hines, IL, Ann Arbor, MI As veterans have equal access to comprehensive healthcare, potential health disparities between ethnic groups are less likely related to differences in medical access. This post-hoc analysis investigated the effect of intensive glycemic control (INT) on CVD events in the VADT among major race/ ethnic groups. The VADT (n=1791), included 1111 non-Hispanic Whites (62%), 307 Hispanics (17%) and 306 non-Hispanic Blacks (17%). Other race/ ethnic combinations (n=67, 3%) were excluded. Hispanics were on average younger, leaner, and had a lower CVD prevalence, but a higher baseline HbA1c (P < 0.01, for overall comparisons between groups). At study-end, the average HbA1c decline with INT was greatest in Hispanics (P = 0.03 for overall comparisons between groups). After adjustment for age, prior CVD, duration of diabetes, history of hypertension, baseline HbA1c, and on treatment BMI and total cholesterol-to-HDL ratio, INT was associated with a ~40% lower rate of CVD events in Hispanics but not in other groups (Figure). However, after adjustment for on trial HbA1c, the effect of INT in Hispanics was no longer significant [HR: 0.92, 0.51-1.70, P=0.80)]. These results suggest that intensive glycemic control may effectively reduce CVD events in Hispanics with advanced type 2 diabetes. 1403-P Handgrip Strength Predicts Cardiovascular Mortality: A Subanalysis of the ORIGIN Trial PATRICIO LOPEZ-JARAMILLO, DANIEL COHEN, DIEGO GOMEZ-ARBELAEZ, HERTZEL GERSTEIN, JACKIE BOSCH, SALIM YUSUF, ORIGIN INVESTIGATORS, Bucaramanga, Colombia, Hamilton, ON, Canada Low muscular strength is a risk factor for cardiovascular disease (CVD) and all-cause mortality in initially healthy individuals. The association between strength and CVD or all-cause mortality in diabetes type 2 (DM2) patients at elevated risk of CV mortality, has not been evaluated. As part of the ORIGIN trial of CVD outcomes and mortality, grip strength (GS) was assessed at baseline in 12516 patients from 40 countries (35% female), mean age 63.6 years (±7.8) with either impaired glucose tolerance/impaired fasting glucose (12%), or DM2 (88%) and followed up for a median of 6.2 years. Raw GS was adjusted for age (GSa) and hazard ratios and 95% CIs for CVD outcomes and mortality per unit increase of GSa were estimated for males and females separately. In males, there were significant negative associations between GSa and stroke, CV death, hospitalised chronic heart failure and total mortality (Table 1). In females, similar patterns were observed and additionally, associations between GSa and total myocardial infarction and revascularisation. In both males and females, associations not weakened by adjusting for BMI, waist or hip circumference. We report in a multi-region cohort of pre DM2 and DM2 patients that higher GS is associated with lower risk of CV and all-cause mortality, with stronger associations observed in females. These findings support the ADA recommendation that DM2 patients participate in strength training. Supported by: U.S. Dept. of Veterans Affairs; NIH (R01-067690), (R01-HL-094775) & PETER BOYLE, MATHIEU BONIOL, ALICE KOECHLIN, MARIA BOTA, CHRIS ROBERTSON, CECILE PIZOT, JAY SKYLER, GEREMIA B. BOLLI, JULIO ROSENSTOCK, PHILIPPE AUTIER, Lyon, France, Glasgow, United Kingdom, Miami, FL, Perugia, Italy, Dallas, TX Effectiveness of glucose-lowering agents depends on a number of factors including the safety profile. A systematic evaluation of the published literature has been undertaken (DIABAMON project) to evaluate the effect of diabetes medications on serious adverse events. Our meta-analysis showed that among diabetes patients recruited to clinical trials, the death rate from all causes fell from SRR=2.16 (95% CI (1.87, 2.48)) in the 1970s, through 1.82 (1.69, 1.96) in the 1980s and 1.69 (1.57, 1.79) in the 1990’s to reach SRR=1.89 (1.33, 1.87) in the 2000’s. There is a two-fold increased risk of cardiovascular disease in diabetes but in high-resource countries the risk of dying from most forms of cardiovascular disease (CVD) is decreasing. Comparing Coronary Heart Disease (CHD) risk in diabetes vs non-diabetes patients through time, the risk in studies which recruited in the 1970’s (SRR=2.27, (1.64, 3.16)) fell among patients recruited the 1980s (SRR=2.02, (1.78, 2.29)) and 1990s (SRR = 1.98, (1.78, 2.29)) to reach SRR=1.58 (1.66, 2.37) among patients recruited to trials in the 2000’s. Whereas rosiglitazone has been associated with an increased risk of CVD, pioglitazone has been shown to reduce risk of death, myocardial infarction and stroke (SRR=0.82, (0.72, 0.94)). Glargine has been shown in randomized Supported by: Sanofi (NCT00069784) ADA-Funded Research & 1405-P Safety of Glucose-Lowering Medications: The Diabetes Adverse Event Monitor (DIABAMON) Project: II Cardiovascular Disease For author disclosure information, see page 829. Guided Audio Tour poster A367 POSTERS & Epidemiology/ Genetics Supported by: NIH EPIDEMIOLOGY—CARDIOVASCULAR DISEASE 0.709 for stroke, 0.681 for MI) and CDS (0.691 for cancer, 0.725 for stroke, 0.699 for MI) alone. The NRI and IDI values were positive and significant for CCI+CDS combinations compared to individual scores. This indicates that the combined scores (CCI+CDS) classified patients into correct strata compared to individual scores. In conclusion, combining CCI and CDS improved prediction of non-skin cancer, stroke and MI in T2DM patients. trials to have no associated increased risk of CVD. A meta-analysis of studies of metformin yields a reduced risk of CVD (SRR=0.85(0.77, 0.95)). Progress has been made in reducing the risk of major CVD and death in diabetes during the past 40 years. There have been improvements in prevention prospects of CVD during the previous decades with the use of statins, better control of blood pressure and the trend to reduce tobacco smoking as well as better management of diabetes. The DIABAMON project is committed to the systematic monitoring of CVD and glucose lowering drugs with rigourous meta-analyses and continuous updates using data from a variety of sources. 1408-P Real-World Cardiovascular Event Rates among High-Risk Adults With Type 2 Diabetes Mellitus KATHLEEN M. FOX, YING WU, JENNIFER KIM, SUSAN GRANDY, Monkton, MD, Wilmington, DE 1406-P This investigation ascertained the incidence and time to first non-fatal myocardial infarction (MI) or stroke among adults with type 2 diabetes mellitus (T2DM) at high risk for cardiovascular disease (CVD) over 3 and 5 years. A retrospective cohort study used data from the US population-based Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD). High-risk respondents with T2DM were stratified into 2 cohorts: 1) established CVD with age ≥40 years, prior MI, prior stroke, atherosclerosis, or peripheral vascular disease, and 2) multiple risk factors (men ≥55 years and women ≥60 years and ≥1 risk factors of hyperlipidemia, hypertension, or current smoking, without prior history of CVD). Proportion of respondents self-reporting a new MI or stroke was calculated and multivariate discrete logistic hazards models for 3 and 5 years of follow-up were developed. Among 2122 T2DM respondents, 56.5% had established CVD (mean age = 65 years, 45% men); 43.5% had no established CVD but multiple risk factors (mean age = 68 years, 49% men). The established CVD cohort had a new MI or stroke event rate of 16.7% during a 3-year follow up period and 20.5% during the 5-year follow-up. For the multiple risk cohort, 17.6% within 3 years and 24.5% within 5 years had an incident MI or stroke. Hazard ratio (HR) of incident MI was 2.1 times higher (95% CI: 1.6-2.8) within 3 years and 1.9 higher (1.5-2.4) within 5 years of follow-up, after adjusting for gender, age, obesity, duration of diabetes, and comorbidities among the established CVD cohort than multiple risk cohort (p <0.001). HR of incident stroke was 2.2 (1.4-3.5) and 1.8 (1.2-2.7) times higher within 3 and 5 years, respectively, after adjustment among the established CVD cohort than multiple risk cohort (p <0.01).In this large US population-based study, T2DM individuals at risk for CVD had significant incidence of MI and stroke. T2DM respondents with established CVD are at higher risk than those with no CVD but have multiple risk factors. POSTERS Epidemiology/ Genetics WITHDRAWN 1409-P Blood Pressure and Stroke Risk among Louisiana Diabetic Patients WENHUI ZHAO, PETER KATZMARZYK, RONALD HORSWELL, YUJIE WANG, JOLENE JOHNSON, WILLIAM T. CEFALU, DONNA H. RYAN, GANG HU, Baton Rouge, LA 1407-P Comparison of Risk Adjustment Methods to Predict Non-Skin Cancer, Stroke and Myocardial Infarction (MI) in Patients With Type 2 Diabetes Mellitus (T2DM) Blood pressure control can reduce the risk of stroke among diabetic patents, however, it is not known if the lowest risk of stroke is among diabetic patients with the lowest blood pressure level. We investigated the prospective race-specific association of different levels of blood pressure at baseline and during follow-up with stroke risk among 17,536 African American and 12,618 White diabetic patients within the Louisiana State University (LSU) Hospital System. During a mean follow up of 6.7 years, 2,949 incident stroke cases were identified. The multivariable-adjusted (age, sex, smoking, income, type of insurance, body mass index, glycosylated hemoglobin, lowdensity lipoprotein cholesterol, estimated glomerular filtration rate, use of antihypertensive drugs, use of diabetes medications, and use of cholesterollowering agents) hazard ratios (HRs) of stroke associated with different levels of systolic/diastolic blood pressure at baseline (<110/65, 110-119/65-69, 120129/70-80 [reference group], 130-139/80-90, 140-159/90-100, and ≥160/100 mmHg) were 1.88 (95% confidence interval [CI] 1.38-2.56), 1.05 (0.80-1.42), 1.00, 1.05 (0.86-1.27), 1.12 (0.94-1.34), and 1.47 (1.24-1.75) for African American diabetic patients, and 1.42 (1.06-1.91), 1.22 (0.95-1.57), 1.00, 0.88 (0.72-1.06), 1.02 (0.86-1.21), and 1.28 (1.07-1.54) for White diabetic patients, respectively. A U-shaped association of isolated systolic or diastolic blood pressure at baseline and during follow-up as well as blood pressure during follow-up with stroke risk was observed among both African American and White diabetic patients. The U-shaped association was confirmed in both patients who were and were not taking antihypertensive drugs. The current study suggests a U-shaped association between blood pressure and the risk of stroke. Aggressive BP control (<110/65 mmHg) and high blood pressure HEMALKUMAR MEHTA, VINAY MEHTA, KIMBERLY G. BRODOVICZ, CYNTHIA J. GIRMAN, Houston, TX, North Wales, PA Risk adjustment tools such as Charlson’s Comorbidity Index (CCI) and Chronic Disease Score (CDS) are used to control for confounding or to predict outcomes in patients with T2DM. The objective was to compare the performance of CCI, CDS and CCI+CDS in predicting non-skin cancers, stroke and MI in patients with T2DM. The Clinical Practice Research Database, electronic medical record data from primary care in UK, was used for this retrospective longitudinal cohort study. Patients diagnosed with T2DM from Jan 1, 2003-Dec 31, 2006 and without prior non-skin cancer (N=74,296), stroke (N=72,872) or MI (N=73,200) were included; separate cohorts were developed for each outcome. The index date was defined as the date of the first T2DM diagnosis. Diagnosis and prescription information up to 1 year prior to index date was used to create CCI and CDS, respectively. Patients were followed for 3 years from the index date to observe outcomes. In addition to traditional concordance (c) statistics from logistics regression, novel reclassification measures (net reclassification index (NRI) and integrated discrimination index (IDI)) were used to compare different risk adjustment models. Non-skin cancers were observed in 6%, stroke in 4.2%, and MI in 2.2% of the respective cohorts. In logistic regression models controlling for age and gender, CCI+CDS performed better at predicting non-skin cancer (c= 0.693), stroke (c=0.726) and MI (c=0.700) compared to CCI (0.690 for cancer, & For author disclosure information, see page 829. A368 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CARDIOVASCULAR DISEASE hypothesis that T2D itself, i.e. hyperglycemia and its underlying metabolic derangement, is the primary cause of increased CVD burden in the T2D. (≥160/110 mmHg) are both associated with an increased risk of stroke among both African American and white patients with type 2 diabetes. Supported by: Louisiana State University Supported by: NIH (R01HL92301) 1412-P 1410-P Reduced Longevity in Parents Linked to Atherogenic Dyslipidemia in T2DM Offspring Various Components of Blood Pressure as Stroke Risk in Japanese Patients With Type 2 Diabetes: Analysis from the Japan Diabetes Complications Study (JDCS) The aim of this study was to determine the best blood pressure index and its cutoff to predict stroke in Japanese patients with type 2 diabetes who have different features regarding the incidence of and risk factors for cardiovascular complications as compared with Western diabetic subjects. Eligible Japanese men and women (n=1771) aged 40-70 years with type 2 diabetes attending 59 institutes nationwide were followed for a planned 8-year period. Performance of systolic, diastolic, pulse and mean arterial blood pressure (SBP, DBP, PP and MAP, respectively) and their various combinations were evaluated as predictors of incident stroke. Hazard ratios (HRs) per 1-SD change in SBP and PP determined by multivariate Cox analysis both significantly predicted stroke (HR 1.31 (95%CI, 1.04-1.65), HR 1.28 (1.03-1.59), respectively), and that for MAP was borderline significant (HR 1.21 (0.97-1.52)), while that for DBP was not predictive. In the tertile analysis, MAP was the only significant index, and this and spline analyses clarified an apparent threshold of 90 mmHg for this index. Comparison with various criteria of hypertension also revealed that MAP≥90 mmHg was more predictive than any other criteria, including the currently used criterion (i.e., SBP≥130 or DBP≥80 mmHg), which was non-significant. This result was also confirmed by Kaplan-Meyer analysis, in which the p value for log rank testing was significant for MAP>90 mmHg but not for the currently used criterion. Reclassification analysis indicated that the new MAP criterion showed an improvement of nearly 10% over the currently used analysis. In conclusions, for Japanese patients with type 2 diabetes, MAP≥90 mmHg was a better criterion than the currently used one for risk evaluation or prediction of stroke; measurement of this parameter should be considered among the clinical approaches to risk reduction among type 2 diabetic patients of an East Asian origin. 1413-P Effect of Regression or Progression in Glucose Tolerance Status on Aortic Stiffness: The ADDITION-PRO Study NANNA B. JOHANSEN, DORTE VISTISEN, KRISTINE FÆRCH, ANNE-LOUISE S. HANSEN, SIGNE S. RASMUSSEN, NIELS WIINBERG, TORSTEN LAURITZEN, ANNELLI SANDBÆK, MARIT E. JØRGENSEN, DANIEL R. WITTE, ADDITIONDENMARK STEERING COMMITTEE, Gentofte, Denmark, Copenhagen, Denmark, Frederiksberg, Denmark, Aarhus, Denmark, Strassen, Luxembourg 1411-P Analysis of the Origins of CVD in the Diabetes Heart Study DONALD W. BOWDEN, JIANZHAO XU, JEFFREY CARR, BARRY I. FREEDMAN, CARL D. LANGEFELD, DAVID HERRINGTON, MAGGIE C.Y. NG, AMANDA J. COX, FANG-CHI HSU, Winston-Salem, NC Compared to individuals with normal glucose tolerance (NGT), individuals with impaired glucose regulation have a higher level of aortic stiffness, a key indicator of cardiovascular disease. However, it is unclear whether changes in glycemic status result in concomitant changes in aortic stiffness. Given different pathophysiological mechanisms underlying isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined IFG+IGT, we examined the effect of progression to diabetes or regression to NGT on aortic stiffness. Through a stepwise diabetes screening program, 342 individuals were identified with iIFG, 241 with iIGT, and 177 with IFG+IGT (54% men, mean age 59.5 years (SD 2.2)). After a mean follow-up of 6.4 years (SD 1.2), a health examination including an oral glucose tolerance test and assessment of aortic stiffness by carotid-femoral pulse wave velocity (aPWV) was performed. Differences in aPWV between individuals who regressed to NGT, who had unchanged impaired glucose regulation, or who progressed to diabetes during follow-up were analyzed using linear regression adjusting for relevant confounders. At follow-up, mean aPWV was 8.8 m/s (SD 2.2). Compared with individuals with stable iIGT, individuals with screen-detected iIGT who progressed to diabetes had a 1.06 m/s (95% CI: 0.25;1.88) higher aPWV at follow-up, whereas individuals who regressed to NGT from iIGT had similar levels of aPWV (difference from stable iIGT: 0.14 m/s (-0.71;1.01)). Among individuals with screen-detected iIFG or IFG+IGT, changes in glycemic status were not significantly associated with aPWV. These results indicate that levels of aortic stiffness are lower among individuals with stable iIGT compared with individuals who progress to diabetes from iIGT, whereas regression from iIGT to NGT during 6 years do People with type 2 diabetes (T2D) have 2-4 fold higher risk of cardiovascular disease (CVD). Multiple hypotheses have been proposed to explain the increased CVD risk, but pathways to this CVD risk remain poorly understood. We evaluated CVD risk in T2D in the Diabetes Heart Study using measures of coronary artery calcification (CAC), clinical risk factors, and genetic data (GWAS). CAC is an established powerful independent predictor of CVD events and mortality and was the measure of CVD burden in this study. Age, gender, and BMI adjusted residuals of (log) CAC were calculated for 1155 European American subjects (967 T2D, 188 non-T2D). When stratified by presence of T2D the distribution of CAC in participants was highly different (Kolmogorov-Smirnov p= 1.6x10-14). Comparable analyses were performed for BP, CRP, lipids, renal function, smoking. The most significant difference was with triglycerides (p=0.003). For many traits there was no difference between T2D and non-T2D, e.g. cholesterol (p=0.10). The cumulative burden of known genetic risk variants for T2D (36 SNPs), lipids (78 SNPs), and CVD (30 SNPs) was calculated. T2D participants had a greater genetic risk burden for T2D (p=0.04) and CVD (p=0.03). Variables that differed between T2D and non-T2D were added as additional covariates in the CAC residual model to assess if they reduced the difference in CAC between T2D and nonT2D. Individual variables had little impact. Addition of all risk variables as covariates reduced the T2D/non-T2D difference in CAC but remained highly significant (p=2.86x10-9). We estimate these genetic and clinical factors account for 32% change in the regression coefficient of T2D effect for CAC. Glucose alone, as a surrogate of T2D, accounts for 43% of the change in CAC. Thus while CVD burden in T2D is associated in part with conventional clinical risk factors and known genetic variants, these findings support the ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A369 POSTERS Background: It is not known whether the fact of having one (or both) parent(s) have not reached an advanced age, alters the phenotype of descendants with type 2 diabetes (T2DM). Aims: To define the cardiometabolic features of T2DM offspring according to parental longevity or brevity. Methods: 405 T2DM patients (mean age 69 (10), M:F 68:32) assessed on parental longevity (paternal and/or maternal lifespan >80 years), divided into 2 groups: a long-lived father and long-lived mother [LLF & LLM] (n=82); and a short-lived father and/or short-lived mother [SLF &/or SLM] (n=323). Atherogenic dyslipidemia (AD) defined as low HDL-C + high TG; AD severity quantified using log[TG]/HDL-C ratio. Homeostatic model assessment (HOMA) of insulin sensitivity [S]; β-cell function [B]; and hyperbolic product [B×S]. Results: Age; DM familial history; education and smoking were similar in both groups. CV familial history and DM duration were increased in [SLF &/ or SLM]: 12% vs. 4% (p 0.0250) and 16 (9) vs. 13 (9) years (p 0.0073) in [LLF & LLM]. Use of glucose-lowering; CV and lipid-lowering drugs was similar in both groups, as were body composition; liver steatosis, hypertension; and BP values. Metabolic syndrome scored higher in [SLF &/or SLM]: 3.79 (1.12) vs. 3.48 (1.12) in [LLF & LLM] (p 0.0257). Fasting insulinemia was higher in [SLF &/or SLM], who were also more insulin resistant than [LLF & LLM], the mean loss in [S] being 10% (p 0.0440). HbA1c was higher, by 0.36 % (3 mmol/ mol) in [SLF &/or SLM] (p 0.0138). LDL-C; non-HDL-C; apoB100; and TG were similar in both groups; whereas HDL-C and apoA1 were higher in [LLF & LLM]: +4 mg/dL and +8 mg/dL (p 0.0233 and 0.0179). Prevalence and severity of AD were both raised in [SLF &/or SLM]: +53% (prevalence) and +13% (log[TG]/ HDL-C) (p 0.0172 and p 0.0067). Conclusion: Uni- or bilateral reduction(s) in parental longevity is linked to insulin resistance; hyperinsulinemia; poorer metabolic control and elevated prevalence, with higher severity, of AD among 1st-degree T2DM descendants. HIROHITO SONE, SHIRO TANAKA, SACHIKO TANAKA, SATORU KODAMA, TATSUMI MORIYA, OSAMU HANYU, KOTARO YOKOTE, SHUN ISHIBASHI, SHINICHI OIKAWA, SHIGEHIRO KATAYAMA, YASUO OHASHI, YASUO AKANUMA, NOBUHIRO YAMADA, JAPAN DIABETES COMPLICATIONS STUDY GROUP, Niigata, Japan, Kyoto, Japan, Kanagawa, Japan, Chiba, Japan, Tochigi, Japan, Tokyo, Japan, Saitama, Japan, Tsukuba, Japan Epidemiology/ Genetics MICHEL P. HERMANS, SYLVIE A. AHN, MICHEL F. ROUSSEAU, Brussels, Belgium EPIDEMIOLOGY—CARDIOVASCULAR DISEASE with previous ACS. Future studies on strategies to prevent CV events in this population are warranted. not affect aortic stiffness. Changes in glycemic status from iIFG/IFG+IGT were not associated with differences in aortic stiffness at follow-up. Supported by: EFSD/Pfizer, Inc. (74550801); Danish Council for Strategic Research Supported by: Takeda Pharmaceuticals International, Inc. 1416-P 1414-P Vitamin E Improves HDL Function in Type 1 Diabetes With the Hp 2-2 Genotype: The HapE Study Cardiovascular Event Rates in a Type 2 Diabetes Population in a Real-World UK Setting: A Large Database Study Using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) TINA COSTACOU, ANDREW LEVY, RABEA ASLEH, RACHEL MILLER, DAN FARBSTEIN, CATHERINE E. FICKLEY, GEORGIA PAMBIANCO, RHOBERT EVANS, TREVOR ORCHARD, Pittsburgh, PA, Haifa, Israel POSTERS Epidemiology/ Genetics AMANDA MCDONELL, STEPHANIE DEVORE, ANUSHINI MUTHUTANTRI, DIRK DEMUTH, CATRINA RICHARDS, YING WU, JENNIFER KIM, London, United Kingdom, Wilmington, NC An increased cardiovascular (CVD) risk has been reported in those with diabetes and the Haptoglobin (Hp) 2-2 vs. the 1-1 genotype. Three clinical trials showed that vitamin E lowers CVD risk by 14-53% in type 2 diabetes and Hp 2-2, potentially through improvements in HDL function, which is thought to be impaired in Hp 2-2; no vitamin E benefit on CVD risk was seen in Hp 1-1 / 2-1 individuals. We thus conducted a randomized, double-blinded, placebo controlled, cross-over trial of vitamin E therapy on HDL function in type 1 diabetes (T1D). Members of two Allegheny County, PA Type 1 Diabetes registries were contacted to assess their willingness and eligibility to participate in a clinical trial of vitamin E supplementation. Willing and eligible individuals were invited to a clinic visit for Hp genotyping. Thirty individuals within each Hp 2-1 and Hp 2-2 were then randomly selected and allocated to receive 400 IU of α-tocopherol acetate daily or placebo in a cross-over manner with an 8 week exposure to each treatment and a 4 week wash-out period between treatments. HDL-associated lipid peroxides (LP) and HDL-mediated cholesterol efflux from macrophages (CE) were assessed prior to and after each treatment. At baseline, LP increased (p-trend=0.08) and CE decreased (p-trend=0.04) linearly with the number of Hp 2 alleles. During the cross-over study, plasma α-tocopherol increased by 60.3% with vitamin E therapy and decreased by 3.8% with placebo (p-difference<0.0001) in Hp 2-1 and 2-2 individuals. Vitamin E therapy also significantly increased CE by 3.3% (vs. 0.92% decrease with placebo) in the Hp 2-2 group (p=0.01) but did not affect CE in the Hp 2-1 group. No effect of treatment was observed for LP in either group. In type 1 diabetes, HDL function worsens with the number of Hp 2 alleles. Vitamin E therapy improves HDL function in the Hp 2-2, but not Hp 2-1, group suggesting a pharmacogenomic effect. These data provide further support for a trial of vitamin E therapy to reduce CVD risk in type 1 diabetes and Hp 2-2. Type 2 diabetes mellitus (T2DM) is associated with increased risk of cardiovascular (CV) disease. The primary aim of the epidemiologic study was to assess time to first major CV event in T2DM patients in a large real-world UK population at high risk for CV events. Retrospective analyses were conducted in the UK CPRD, an anonymised, longitudinal primary care database, linked to secondary care and mortality data. Patients with a T2DM diagnosis and at least 1 physician visit recorded 1 January 2005 - 31 October 2011 were screened at first recorded physician visit (index) for study inclusion. Criteria for inclusion were T2DM patients aged ≥40 years, HbA1c ≥6.5% and either established CV disease and/or presence of multiple CV risk factors. Eligible patients were followed up to 31 October 2011 for outcome evaluations. Study outcomes were calculated using the Kaplan-Meier estimator. 21,560 eligible patients were identified (57% male; mean age: 70.1 years; total follow up period for patient population: 121,523 years). The probability of experiencing a CV event (defined as fatal/non-fatal myocardial infarction or stroke) by 1, 3, 5 and 6 years post-index was 4.4%, 9.4%, 13.4% and 15.3%, respectively. Patients with prior CV events (n=10,154; mean age: 71.1 years) had a probability of experiencing a subsequent CV event of 7.2%, 14.6%, 19.9% and 22.3% by 1, 3, 5 and 6 years post-index, respectively. Patients with multiple risk factors without prior CV events (n=11,406; mean age: 69.2 years) had a probability of experiencing a CV event of 1.9%, 4.7%, 7.7% and 9.0% by 1, 3, 5 and 6 years, respectively. In this real-world study, T2DM patients with history of CV events or multiple risk factors were observed to have high rates of CV events. Patients with a history of prior CV events have a higher probability of experiencing future CV events compared to patients with no prior CV events, but presenting with risk factors. 1417-P Plasma Fibrinogen Level as a Predictor of Cardiovascular Diseases, Independent of Diabetes, in a Population-Based 16-Year Prospective Study in Hong Kong 1415-P Incidence, Costs of Cardiovascular Rehospitalization among Diabetes Patients With Pre-Existing Acute Coronary Syndrome: A Retrospective Database Study ELAINE HUI, TAI HING LAM, WING SUN CHOW, CHUN YIP YEUNG, YU CHO WOO, CAROL FONG, AIMIN XU, HUNG FAT TSE, BERNARD MY CHEUNG, KAREN SIU LING LAM, Hong Kong, China MORGAN BRON, HUAN HUANG, JAY LIU, PENNY FLECK, DUYGU BOZKAYA, MICHAEL MUNSELL, JOE MENZIN, Deerfield, IL, Waltham, MA Recent evidence from prospective studies in the United States and Europe suggest plasma fibrinogen level is useful for prediction of cardiovascular risk in addition to conventional risk factors. As one of the acute-phase reactant proteins, fibrinogen increases in response to the inflammatory process of atherosclerosis. Baseline data of the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS), commenced in 19956, showed close positive relationship between circulating fibrinogen levels and diabetes, a major cardiovascular risk factor. In this study, we examined whether plasma fibrinogen was predictive of incident cardiovascular diseases (CVD) over 15.9 years (IQR 15.5 – 16.5) in the CRISPS cohort, and whether the prediction was dependent on its association with diabetes. Of a total of 2774 subjects, 374 had confirmed incident CVD. In addition to male sex and age, baseline body mass index (BMI), waist circumference (WC), fasting glucose, 2-hour glucose after oral glucose tolerance test, insulin resistance index HOMA-IR, systolic and diastolic BP, triglycerides (TGs), high-density lipoprotein, the presence of diabetes, hypertension, dyslipidaemia, and fibrinogen level were all predictive of incident CVD over 15.9 years (all p<0.001). Fibrinogen level correlated positively with fasting glucose, HOMA-IR, BMI, WC, systolic and diastolic BP, and TGs after sex and age adjustment (all p<0.001).On multivariate analysis, baseline age, WC, diabetes, hypertension, and fibrinogen level were independent risk factors (p≤0.001) for incident CVD. In conclusion, the findings from this 16-year prospective study confirmed plasma fibrinogen level as a strong predictor of CVD, independent of diabetes, in community-based Chinese adults. Patients with diabetes mellitus (DM) and pre-existing acute coronary syndrome (ACS) are at high risk for subsequent cardiovascular (CV) events. Our objective was to understand the incidence, costs and factors associated with CV rehospitalization among DM patients following ACS admission. Using the Truven Health Analytics MarketScan® database, patients with DM and receiving an antidiabetic treatment other than insulin between 2006-2010 were identified. Patients must have had an ACS hospitalization (acute myocardial infarction [MI] or coronary revascularization) following the earliest DM diagnosis and were required to be enrolled for ≥1 month. The proportion of patients with a subsequent CV event (defined as having ≥1 inpatient claim for acute MI, stroke, or coronary revascularization) and the rate of CV events (per 100 person-years [PYs]) were evaluated, along with CV-related and all-cause costs. Logistic regression was conducted to identify factors associated with the likelihood of having a CV rehospitalization. 55,095 DM patients with an ACS admission were identified (mean age 66 years, 38% female), with a mean (median) follow-up of 19 (16) months. 21% of patients had ≥1 CV event during follow-up, with a rate of 21.4 CV events per 100 PYs. Adjusting for follow-up time, the likelihood of having a CV event increased with greater Charlson comorbidity score, longer stay of the index hospitalization, and having an MI diagnosis for the index hospitalization. Bypass surgery during the index hospitalization and taking more than one antidiabetic drug were significantly associated with lower CV risk. Mean monthly CV-related (all-cause) follow-up cost among all patients (regardless of whether they had a subsequent event) was $1,092 ($2,965). CV-related rehospitalization is fairly common and costly among DM patients Supported by: Hong Kong Research Grant Council (T12-705/11) & For author disclosure information, see page 829. A370 Guided Audio Tour poster ADA-Funded Research 1420-P Long-Term Cardiovascular Outcomes With Exenatide Twice Daily Compared to Insulin: A Retrospective Observational Study MARCO DAURIZ, ALESSANDRO MANTOVANI, ISABELLA PICHIRI, RICCARDO RIGOLON, GIACOMO ZOPPINI, ENZO BONORA, GIOVANNI TARGHER, Verona, Italy SANJOY K. PAUL, STEVEN P. MARSO, DAVID MAGGS, KERENAFTALI KLEIN, JENNIE H. BEST, Brisbane, Australia, Kansas City, MO, San Diego, CA Treatment with exenatide has shown beneficial effects on cardiovascular (CV) risk factors in patients (pts) with T2DM. Long-term effects of treating T2DM patients (pts) with GLP-1 receptor agonists on CV outcomes remain limited. Using the GE Healthcare database, we evaluated the risk of heart failure (HF), myocardial infarction (MI) and stroke in pts initiating exenatide twice daily (EBID; n=2795) or any insulin (INS; n=51,547) in routine clinical practice. A cohort of 54,342 pts who received a first prescription of EBID or INS between June 2005 and May 2009, combined with oral antidiabetes agents (OADs), was selected and followed for a minimum of 3 y with minimum 6 mo under the same drug regimen. The possible effects of EBID vs INS on CV events in this age-matched cohort were evaluated using a stratified Cox regression model, adjusted for age, sex, race, history of CV disease, OADs, and cardio-protective medications. EBID/INS pts were 39%/47% men, 56/59 y of age, 54%/48% white, 11%/12% history of CV disease, 89%/61% MET, 55%/46% SFU, 47%/33% TZDs, 74%/82% ACE-ARB, 43%/56% β blocker, and 85%/84% statins. During median 4.3 y follow-up for EBID and 4.2 for INS, 2.1%/5.8%, 0.5%/0.9% and 0.9%/2.1% had HF, MI and stroke events respectively. CV event rates per 1000 person-years were significantly lower among patients treated with EBID vs INS (HF: 4.8 vs 13.6, MI: 1.1 vs 2.1, stroke: 2.0 vs 4.9). Compared to INS, pts treated with EBID had significantly lower risk of HF by 53% (HR CI: 0.36, 0.61) and MI/stroke by 48% (HR CI: 0.38, 0.72). Patients with a history of CV disease had a 47% (HR CI: 1.35, 1.60) increased risk of HF and 70% (HR CI: 1.50, 1.91) increased risk of MI/stroke compared to pts without a history of CV disease. Potential limitations of this analysis include misclassification of outcome and residual confounding. In this retrospective database study, treatment with EBID resulted in significantly lower risk of HF and MI/stroke during 4-y follow-up compared with INS. Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are two pathologic conditions that are highly prevalent in Western countries and that share multiple cardiometabolic risk factors. Presently, the published research on the association between NAFLD (or liver function tests) and AF is sparse. In particular, there is a lack of available information on the relationship between NAFLD and AF in people with type 2 diabetes (T2DM), a group of individuals in which these two diseases are highly prevalent. We studied a hospital-based sample of 702 Caucasian patients with T2DM (M/ F=379/323, mean age 66 years) discharged from our Division of Endocrinology during 2007-2011. The diagnosis of AF was confirmed in affected participants by experienced cardiologists. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver diseases. Of the 702 patients included in the study, 514 (73.2%) of them had NAFLD and 85 (12.1%) had persistent AF. NAFLD was associated with an increased risk of prevalent AF (odds ratio [OR] 3.04, 95% CI 1.5-6.0, P<0.0001). Adjustments for age, sex, BMI, hypertension, electrocardiographic left ventricular hypertrophy, chronic kidney disease, statin use, prior history of coronary heart disease, heart failure, valvular heart disease, chronic obstructive pulmonary disease and hyperthyroidism did not appreciably weaken the association between NAFLD and AF (adjusted-OR 4.39, 95%CI 2.0-9.3, P<0.0001). The significance of this association was consistent in all subgroups evaluated. In conclusion, this study is the first to document that NAFLD is associated with an increased prevalence of AF in a large hospital-based sample of patients with T2DM. This association appears to be independent of important clinical risk factors for AF. Future research is needed to corroborate these findings and to determine whether NAFLD predicts the incidence and persistence of AF in people with T2DM. 1419-P Temporal Trends in Subclinical Coronary Artery Disease (CAD) Among Non-Elderly Adults: A Population-Based Study 1421-P CARIN Y. SMITH, KENT R. BAILEY, VERONIQUE L. ROGER, PETER N. NEMETZ, JANE A. EMERSON, PASQUALE J. PALUMBO, CYNTHIA L. LEIBSON, Rochester, MN, Vancouver, BC, Canada Gender Effect on Risk of First-Ever Ischemic Stroke and Early Mortality in Hospitalized Diabetic Patients The argument that obesity and diabetes (DM) epidemics have not impacted CAD prevalence is based on continued declines in hospitalized myocardial infarction and heart disease deaths. This fails to account for subclinical CAD, especially in the non-elderly. Using non-natural deaths (96% autopsy rate), we previously showed that declines in CAD grade since 1981 ended in the mid-1990s. Our present aim was to predict population trends in CAD grade using trends in CAD risk factors and applying associations between CAD risk factors and grade in autopsied decedents. We used Rochester Epidemiology Project resources to identify all Olmsted County, MN, residents age 16-64 who died of non-natural causes 1981-2009 with CAD grade at autopsy (N=551) and a random sample of 1244 Olmsted County residents age 16-64, 1981-2009. For each group, we reviewed all medical records and estimated temporal trends in CAD risk factors, including age, sex, blood pressure (BP), BP medication use, DM (qualifying glucose or medication), body mass index (BMI), smoking, and hyperlipidemia. We used multiple regression of CAD grade on risk factors in decedents to predict CAD grade in the population sample, and tested for linear and non-linear temporal trends in predicted grade. In both groups, BP values and smoking declined over time (all p <.03); while BP medication use, DM, BMI≥30, and hyperlipidemia increased (p <.05, except DM in decedents). Predicted CAD in the population (estimated grade/year [95% CI], p value) revealed an increased trend 1981-2009 (linear slope =.0011 [-.0004, .0026], p=.15); a non-linear model provided a better fit (p=.055), with a trend for decrease 1981-1986 (-.0139 [-.0321, .0043], p=.14) followed by an increase 1987-2009 (.0026 [.0004, .0048], p=.022). Despite continuing declines in smoking and BP values, an autopsy-based model predicts an increased rate of subclinical CAD for a random sample of non-elderly adults, possibly due to rising obesity, DM, and need for BP medication. LAURA POLICARDO, PAOLO FRANCESCONI, FRANCESCO CIPRIANI, ROBERTO ANICHINI, LUCIA TURCO, FLAVIA FRANCONI, STEFANO DEL PRATO, GIUSEPPE SEGHIERI, Firenze, Italy, Pistoia, Italy, Sassari, Italy, Pisa, Italy Ischemic stroke occurs at higher rate among diabetic patients and diabetes worsens stroke prognosis in terms of mortality and disability. Aim of this study is to evaluate gender differences in the association between diabetes and hospitalization for first-ever ischemic stroke (FEIS). For this purpose we reviewed the database of all discharges from hospitals of Tuscany, Italy (3,393,538 inhabitants, 2011 census), during the period 2003-2011. ICD9-CM codes 433.xx, 434.xx, 436.xx identified ischemic stroke, and 250.xx diabetes mellitus. FEIS identified those discharged only once or discharged for the first time in cases of multiple admissions. In total alive discharged population with FEIS diagnosis (n=62,199; 30,557 males and 31,642 females) age-adjusted odds ratio (OR: 95% CI) of FEIS was significantly higher in diabetic patients and was greater in male diabetic patients than in females [OR:1.38; (1.34-1.42) vs. 1.26; (1.22-1.30)]. Such increased risk was observed in each age class, save for those>70yr where risk was higher in women, declining progressively with age, except among women whose risk of association FEIS-diabetes peaked in age class 51-60 yr [OR:2.10; (1.81-2.43)]. Adjusted OR of 30-days mortality risk was unmodified in age class ≤ 70 yr, while in age class >70 yr was about 20% lower in male diabetic patients with stroke than in non-diabetic subjects of same age class [OR:0.81; (0.72-0.91)], and conversely was higher in women compared to diabetic men [OR:1.49; (1.31-1.71)]. Finally, association diabetes-mortality in FEIS did not change with time for both sexes. In conclusion hospitalization risk for FEIS is ~ 3040% higher in diabetic patients, and is significantly greater in diabetic men than in women. Risk declines with age, reaching its maximum in females during perimenopausal life. Thirty-days diabetes-associated mortality risk is lower in male diabetic patients aged above 70 yr, is higher in women than in men in this age class, being unmodified over time. Supported by: Fondazione Cassa di Rsparmio di Pistoia e della Lucchesia ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A371 POSTERS 1418-P Non-Alcoholic Fatty Liver Disease Is Associated With an Increased Prevalence of Atrial Fibrillation in Patients With Type 2 Diabetes Epidemiology/ Genetics EPIDEMIOLOGY—CARDIOVASCULAR DISEASE EPIDEMIOLOGY—CARDIOVASCULAR DISEASE to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been shown to be associated with dyslipidemia in adults. However there are few general population studies examining this association in children. In this context, we examined the association between serum PFOA and PFOS levels and dyslipidemia in a nationally representative sample of US children. A cross-sectional study was performed on 815 participants ≤18 years of age from the National Health and Nutrition Examination Survey 1999-2008. The main outcome was dyslipidemia, defined as total cholesterol >170 mg/dL, lowdensity lipoprotein cholesterol (LDL-C) >110 mg/dL, high-density lipoprotein cholesterol (HDL-C) <40 mg/dL or triglycerides >150 mg/dL. We found that serum PFOA and PFOS was positively associated with high total cholesterol and LDL-C, independent of age, sex, race-ethnicity, body mass index, annual household income, physical activity and serum cotinine levels. Compared to subjects in quartile 1 (referent), the multivariable-adjusted odds ratio (95% confidence interval) for high total cholesterol among children in quartile 4 was 1.16 (1.05-2.12) for PFOA and 1.53 (1.11-1.64) for PFOS. PFOA and PFOS were not significantly associated with abnormal HDL-C and triglyceride levels. Our findings indicate that serum PFOA and PFOS are significantly associated with dyslipidemia in children, even at the lower “background” exposure levels of the US general population. 1422-P Comparative Safety and Effectiveness of Sitagliptin in Patients With Type 2 Diabetes and Heart Failure POSTERS Epidemiology/ Genetics DANIALA L. WEIR, A. SENTHILSELVAN, JASON R. DYCK, JASJEET K. SANDHUMINHAS, FINLAY A. MCALISTER, DEAN T. EURICH, Edmonton, AB, Canada Sitagliptin belongs to a new class of antidiabetic agents called incretins, which are hypothesized to have pleiotropic effects on the cardiovascular system as well as heart failure specific effects. The objective of this study was to determine if the use of sitagliptin was associated with any benefit or risk on clinical outcomes in a population-based cohort of patients with type 2 diabetes and incident heart failure. Using a large commercially insured US claims and integrated laboratory database, 11,967 subjects with type 2 diabetes and incident heart failure were identified through physician claims, hospital discharge abstracts, and/or ambulatory care visits based on ICD-9 CM codes. Our populationbased cohort was followed from January 1, 2004 until death, termination of medical insurance, or December 31, 2010. Time-varying multivariable Cox proportional hazards models were used to asses differences in all-cause mortality. Average age of subjects was 56 years, 39.6% were female, and mean duration of follow-up time was 1.94 years. In total, 653 subjects died (5.5%). No association between all-cause death and sitaglitpin use was observed compared to other glucose lowering agents. After adjustment for demographics, clinical & laboratory data, pharmacy claims, health care utilization and time-varying propensity scores, any sitagliptin use was not associated with a statistically significant increase in mortality (adjusted HR 0.64, 95% CI 0.37-1.12) compared to no sitagliptin use. Similarly, compared to metformin/sulfonylurea combination therapy, sitagliptin combination therapy was not associated with an increase in mortality (adjusted HR 1.01, 95% CI 0.40-2.56). Sitagliptin therapy was not associated with excess risk of all-cause death among patients with type 2 diabetes and heart failure. Supported by: 5T32HL090610-04; 5R03ES018888-02 1425-P Relatively Small Increases in LDL-Cholesterol are Associated With Elevation in Coronary Heart Disease Risk in Diabetes SWAPNIL RAJPATHAK, GLENN DAVIES, SAMUEL S. ENGEL, North Wales, PA While an elevated circulating level of low density lipoprotein cholesterol (LDL-C) is a known risk factor for developing coronary heart disease (CHD) among patients with type 2 diabetes, it is unclear whether relatively small increases in LDL-C levels have a meaningful impact on this risk, especially in the longer term. Using a Markov CHD risk model based on Framingham risk equations, we projected the number of CHD events in the US population with diabetes using data from the 2009-10 National Health and Nutritional Examination Survey (NHANES) (age≥40 years; 50% females, mean LDL-C of 101 mg/dl; 25.7% with history of CHD), in relation to a 5, 10 or 15% increase in LDL-C levels. CHD events for individual patient profiles from NHANES were weighted by each individual’s sampling weight to provide national estimates. CHD events included fatal and non-fatal myocardial infarction and angina. For LDL-C increases of 5, 10 and 15%, the model projected a relative increase of 2.7%, 5.3% and 7.9% in total CHD events over 5 years. Over a 10 year period, these estimates were 2.7%, 5.4% and 8.1%. This increase in CHD risk could potentially translate to additional 108,361 nonfatal and 12,040 fatal cases of CHD for a 15% LDL-C increase among US diabetic population aged≥40 years over 10 years. These results suggest that even relatively small increases in LDL-C may elevate CHD risk in diabetes and could impose significant clinical and economic burden. Interventions among patients with diabetes that may potentially increase circulating lipid levels warrant cautious use in this high risk population. 1423-P Compliance With Anti-Diabetic Medication Improves Cardiovascular Outcomes in Patients With Type 2 Diabetes SANGMO HONG, KYUNGJOO KIM, MI KYUNG KIM, JEONG-TAEK WOO, YOUNG SEOL KIM, SEI HYUN BAIK, MOON SUK NAM, KWAN WOO LEE, JINHEE KIM, YURI KIM, YONGSOO PARK, Gyeonggi, Republic of Korea, Seoul, Republic of Korea, Incheon, Republic of Korea, Suwon, Republic of Korea Objective: Type 2 diabetes (T2D) is associated with increased mortality and morbidity from macrovascular disease. We assessed compliance with anti-diabetic drug therapy and estimated its effect in reducing the risk of macrovascular complications in T2D patients recruited from a prospective cohort study (Korea National Diabetes Program (KNDP) database (2005-2010)). Research Design and Methods: We used the Korean Health Insurance Review and Assessment Service (HIRA) database as an independent source of data related to the KNDP cohort database in order to compensate for the incompleteness of prospective follow-up due to compliance. Compliance with anti-diabetic medication was assessed by calculating the rates of prescription refills from the HIRA database for a uniform period of 1 year. Cox regression models of the effect of drug compliance were also compared. Results: Of the 3842 eligible patients, 261 (6.8%) experienced cardiovascular events during the follow-up period. Indeed, in multivariate models drug compliance in both genders had an independent effect on the development of new cardiovascular events. According to a covariate-adjusted model, the predictors of cardiovascular disease were age (p<0.001), duration of diabetes (p<0.001), hypertension (p=0.008) and anti-diabetic drug compliance (p<0.001). Furthermore, the third of patients with the highest drug compliance achieved a reduction of 75% (95% CI = 0.17-0.36) in cardiovascular disease risk, and the middle third achieved a reduction of 59% (95% CI = 0.30-0.57) compared to patients with the lowest drug compliance. Conclusions: This study has shown that improving compliance to antidiabetic medication reduces the risk of macrovascular complications in patients with T2D. 1426-P High Mortality and Cardiovascular Event Rates Within Type 2 Diabetes Mellitus (T2DM) Patients With Established Cardiovascular Disease (CVD) or CVD Risk Factors in a Large U.S. Database DAVID M. KERN, STEPHANIE DEVORE, YING WU, JENNIFER KIM, BOAZ HIRSHBERG, OZGUR TUNCELI, BINGCAO WU, Wilmington, DE T2DM-related comorbid conditions, such as hypertension and dyslipidemia, and prior CVD events contribute to the development of cardiovascular (CV) complications, including stroke, myocardial infarction (MI) and death. This study described CV outcomes and mortality among patients with established CVD and CVD risk factors. 368,581 T2DM patients aged ≥40 years were identified in the HealthCore Integrated Research Environment from 1/1/2007 to 4/30/2011 and were followed from first diagnosis (index date) until loss of eligibility or death. Patients were classified as established CVD [Group 1]: MI, stroke, peripheral vascular disease, coronary heart disease, congestive heart failure, or revascularization in the year prior to index; or CVD risk [Group 2]: age risk (men ≥55 years, women ≥60) and with a prior diagnosis for either dyslipidemia or hypertension. 177,140 Group 1 (mean age: 68.1 y) and 191,441 Group 2 (mean age: 66.2 y) patients met the selection criteria. Both groups were 57% men. Patients were followed up to 5 years, and outcomes were analyzed via Kaplan-Meier analysis (figure 1). Supported by: Korea Healthcare Technology R&D Project 1424-P The Association between Perfluoroalkyl Chemicals and Serum Lipid Levels in Children SARAH D. GEIGER, JIE XIAO, ALAN DUCATMAN, STEPHANIE FRISBEE, KIM E. INNES, ANOOP SHANKAR, Madison, WI, Morgantown, WV Dyslipidemia in children is associated with accelerated atherosclerosis and earlier cardiovascular disease development. Environmental exposure & For author disclosure information, see page 829. A372 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CARDIOVASCULAR DISEASE High mortality rates and CV events were observed for both cohorts during follow-up. Patients with established CVD had much higher mortality rates compared with those with CVD risk alone - reaching more than 20% after 4 years. T2DM patients are at significant risk for mortality and CVD events. 1428-P Comparative Effectiveness of Sulfonylurea and Metformin on Risk of Cardiac Events in Middle-Aged Adults With Type II Diabetes Mellitus 1429-P Usefulness of Fatty Liver Index as Predictor for Coronary Artery Stenosis in Subjects With Low to Intermediate Framingham Risk Score Supported by: AstraZeneca CHANG HEE JUNG, JOONG-YEOL PARK, JAECHAN LEEM, WOO J.E. LEE, HONGKYU KIM, Seoul, Republic of Korea Historically, the Framingham risk score (FRS) has been the dominant method of risk stratification. However, considerable number of subjects with substantial atherosclerosis will be missed if they are excluded from further screening because they are in the Framingham low to intermediate-risk category. Fatty liver disease (FLD), especially nonalcoholic fatty liver disease, are frequently associated with risk factors for atherosclerosis. Recently, a simple scoring system called fatty liver index (FLI) was developed as a predictive indicator of FLD. In this study, we aimed to evaluate whether FLI can be useful tool for the detection of subclinical coronary atherosclerosis detected by coronary multidetector computed tomography (MDCT) in subjects with low to intermediate FRS. We collected the data of asymptomatic 1,272 subjects (≥20 yr of age; mean age 52.8 yr) who participated in a routine health screening examination of Asan Medical Center (Seoul, Republic of Korea). Significant coronary artery stenosis defined as >50% stenosis. The Agatston score was used as the coronary artery calcium score (CACS) and was categorized as followings: CACS ≤100 (none to mild) and CACS >100 (moderate to severe). We could observe that more subjects with significant coronary stenosis and moderate to severe CACS were included in the group with FLI≥60 (FLI +) than in the group with FLI <20 (FLI -). The odds ratios (ORs) for the presence of significant coronary stenosis and moderate to severe CACS were significantly higher in the group with FLI≥60 than in the group with FLI <20 even after adjustment for various confounding variable including surrogate measure of insulin resistance. Our results suggest that FLI as a simple surrogate indicator of hepatic steatosis can be useful in identifying subjects with significant subclinical coronary atherosclerosis even though they are classified as Framingham low to intermediate-risk category. 1427-P Neck Circumference as a Measure of Central Obesity: Associations With Metabolic Syndrome Beyond Waist Circumference in Chinese Population JUAN LIU, ZHENZHEN HONG, AILING CHEN CHEN, YANBING LI, Guangzhou, China Neck circumference (NC), a simple and time-saving screening measure to identify obesity is reported to be positively correlated with the factors of the metabolic syndrome (MetS). This study was conducted to evaluate the correlation between the NC and components of MetS and wether it add informations to that provided by waist circumference (WC). Cross-sectional analysis of a population sample of 333 men and 438 women, aged 40~65 years, was conducted. Eligible subjects were healthy subjects who voluntarily received routine comprehensive check-ups including magnetic resonance imaging(MRI) scan analyses of abdominal Adipose tissue from February to June 2012 at Diabetic Center of the First Affiliated Hospital of Sun Yat-sen University. MetS was identified based on modified criteria of the ATP-III. NC was significantly and positively associated with WC and body mass index (BMI) (rə0.6), visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area measured by MRI (rə0.3), serum triglyceride, blood pressure and homeostatic model-assessed insulin resistance, and inversely with SAT/ VAT ratio (SVR) (rə-0.3) and HDL-cholesterol (rə-0.4) both in men and women. Sex and age-adjusted NC was associated significantly with MetS, at a about 1.5-fold increased likelihood for 1 standard deviation (SD) increment. After further adjustment for WC, smoking status, alcohol use and menopausal (women only), a significant residual odds ratio (OR, 1.2 [95%CI 1.1; 1.5]) persisted in women, but not in men. The reciever operating characteristic (ROC) cut-off value for NC, as an indicator for MetS, was calculated as 37.7cm in men and 32.7cm in women. NC was shown to be associated with metabolic risk factors in Chinese men and women and contributed to MetS likelihood beyond WC in women. We suggest the use of neck circumference as a novel, simple, practical and reliable anthropometric index in predicting MetS, especially in women. ADA-Funded Research & 1430-P Prevalence of Aspirin Resistance in Diabetic Patients Is Associated With Daily Dose: A Systematic Review SCOT H. SIMPSON, AHMED ABDELMONEIM, DIMA OMRAN, TRAVIS FEATHERSTONE, Edmonton, AB, Canada Clinical trials have shown that ≤100 mg aspirin daily is not effective for primary prevention of cardiovascular events in diabetic patients. However, For author disclosure information, see page 829. Guided Audio Tour poster A373 POSTERS Considerable controversy exists about the differential effect of oral diabetic agents on the risk of cardiovascular disease (CVD) and mortality in patients with type II diabetes. The comparative risk of CVD and mortality with metformin and sulfonylureas is not well-described in the overall population of adults age 40-64. The purpose of this study was to evaluate the relative likelihood of cardiac events and death associated with the use of sulfonylurea and metformin monotherapy in middle-aged patients with type II diabetes. A retrospective-cohort study, based on propensityscore matching, analyzed patients in a large nationally representative administrative claims database. The sample consisted of Medicaid and Commercial patients aged 40-64 years who were new users of metformin or sulfonylurea (glyburide and glipizide) monotherapy between 2006 and 2010. Patients were continuously enrolled for 12-months in the health plan before initiation of diabetic treatment. Multivariate survival analysis (cox proportional hazards model) was performed and patients were followed to the time of adverse event or up to 180 days after the index date, and were censored if switched to another drug or disenrolled from the healthplan. The study population included 20,093 patients identified as new users of sulfonylurea (female = 51.1%, mean age = 53.7 [± 6.9]) and 20,093 patients identified as new users of metformin (female = 48.9%, mean age = 53.8 [± 6.7]) after matching. Patients prescribed sulfonylurea had a significantly higher risk of CVD and all cause mortality compared to metformin (HR = 1.25, 95% CI: 1.18-1.32) after controlling for potential confounders. This study provides new evidence suggesting that use of sulfonylureas increases the risk of cardiac events and mortality in middle aged patients with type II diabetes, and indicates caution be used in prescribing these drugs in this patient population. Epidemiology/ Genetics CHRISTIE TEIGLAND, ALEXIS PARENTE, SANDHYA MEHTA, BARTON JONES, PING CHEN, JOHN SCOGGINS, Bowie, MD EPIDEMIOLOGY—CARDIOVASCULAR DISEASE 10mg/day (n=25), rosuvastatin 5mg/day (n=35), or pisuvastatin 2mg/day (n=26). We evaluated dietary TG increase=postprandial TG - fasting TG at baseline (ΔTGbase) and 4 weeks after statin administration (ΔTGstatin), and ΔTG ratio=(postprandial TG / fasting TG with statin) / (postprandial TG / fasting TG at base). Change of ΔTG by statin administration (ΔTGstatin - ΔTGbase) was inversely correlated with ΔTGbase (Figure), and was significantly smaller in patients group of ΔTGbase ≥ 60mg/dl than in the group of ΔTGbase < 60mg/ dl (-87.5±84.7 vs. 20.3±58.1, p<0.0001). ΔTG ratio was also smaller in the former group than the later (0.72±0.27 vs. 1.25±0.55, p<0.0001). Statins strongly suppressed postprandial TG increase, especially in patients with greater postprandial TG increase. This suppressive effect of statins, resulting in lowering sdLDL level all day long, might be a possible mechanism of beneficial effects of statins. pharmacologic evidence suggests these patients require >100 mg daily for adequate antiplatelet activity. This systematic review examined the relationship between prevalence of resistance in diabetic patients and daily aspirin dose. We searched 3 electronic databases from inception to July 2012 using database-appropriate terms for aspirin, resistance, and diabetes; clinical trial registries; and reference lists of included studies. Studies were included if resistance was determined using a platelet response measurement and the prevalence of resistance was reported according to daily aspirin dose and diabetes status. We included 19 crosssectional studies, 4 cohort studies, and 3 randomized controlled trials. Platelet response was measured using light transmission aggregometry in 12 studies, PFA-100 in 10, VerifyNow in 3, and serum thromboxane B2 levels in 1. Diabetic patients were more likely to have aspirin resistance compared to non-diabetic patients (pooled RR 1.34; 95% CI 1.03-1.73). Prevalence of resistance varied significantly (p<0.001) according to daily aspirin dose. Aspirin Dose Group 75-100 mg 150-250 mg 300-325 mg Studies 19 8 8 Patients 1370 248 230 Resistant, n (%) 335 (24%) 13 (5%) 39 (17%) Although these observations need to be verified in a clinical trial, the possibility that 1 in 4 diabetic patients are resistant to a commonly used aspirin dose could have significant implications on its overall effectiveness. POSTERS Epidemiology/ Genetics 1431-P The Effect of Maximum Body Weight in Lifetime on the Development of Coronary Artery Disease in Type 2 Diabetes: MAXWEL-CAD Study SOO LIM, EUN SHIL HONG, MIN JOO KIM, EUN KY KIM, YOON JI KIM, EUN ROH, TAE JUNG OH, MIN KYEONG KIM, SU MIN HONG, SUNG HEE CHOI, KYONG SOO PARK, HAK CHUL JANG, Seongnam, Republic of Korea, Seoul, Republic of Korea We investigated association of rate of weight gain with subclinical coronary artery disease (CAD) in newly detected patients with type 2 diabetes (T2D). Obesity is well known to be associated with CAD. However, the relationship between the rate of weight gain to development of CAD in T2D patients has received less attention. With 1724 consecutive Korean subjects aged ≥30 years newly diagnosed with T2D, we evaluated degree of coronary artery stenosis, multivessel involvement, plaque characteristics, and coronary artery calcium score (CACS) using 64-slice cardiac computed tomography angiography. Data of body weight at age 20 years (Wt 20y) were obtained from participants’ document. Participants recalled their maximum weight (Wtmax) prior to T2D diagnosis and age at maximum weight (Agemax_wt). The rate of weight gain (Ratemax_wt) was calculated from magnitude of weight gain (ΔWt = WtmaxWt 20y) divided by ΔTime (Agemax_wt -20 years). Prevalence of significant coronary artery stenosis (≥50%), multivessel involvement (≥2), any plaques, and CACS ≥ 100 were 11.4%, 16.8%, 19.7%, and 12.8%, respectively. The Wt 20y and Wtmax were 60.1±10.5kg and 73.0±11.5kg, respectively. The Agemax_wt was 41.3±10.7 years and the log-transformed (Ratemax_wt +1) was 0.59 ± 0.56 kg/year. After adjusting for cardiovascular risk factors including BMI, the highest quartile of logtransformed (Ratemax_wt+1) was significantly associated with coronary artery stenosis, multivessel involvement and presence of any plaque, particularly of mixed and non-calcified plaques. This finding supports public health recommendation of preventing rapid weight gain from early adulthood for reduction of vascular complications in T2D. 1433-P WITHDRAWN 1432-P Statins Strongly Suppress Postprandial Increase of Serum Triglyceride, Especially in Patients With Greater TG Increase—Possible Mechanism of Beneficial Effects of Statins TADAMASA WAKABAYASHI, YOSHIHARU FUJIMORI, MEIKO SAKURADA, MASAYUKI YOSHIMURA, HIRONORI MURAOKA, MASARU HATANO, MASEI SUDA, TAKASHI ENDO, TAKU IMAI, MASAYA SAKURADA, Chino, Japan, Narita, Japan, Yamaguchi, Japan, Tokyo, Japan Statins decrease small dense low density lipoprotein (sdLDL), which production is stimulated in response to an increase of triglyceride (TG). We think that it is important to suppress dietary increase of TG (ΔTG). We evaluated fasting and 3-hour postprandial lipid profiles in 86 patients with dyslipidemia (61 males, 25 females), at baseline and 4 weeks after statin administration. Patients were randomly assigned to atorvastatin & For author disclosure information, see page 829. A374 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CARDIOVASCULAR DISEASE 1434-P 1436-P Associations of Cardiovascular Disease With Microangiopathy in Diabetes Insulin Resistance and Hypertension in Nondiabetic Asian Indian Adults SATSUKI KAWASAKI, HARUO MISAWA, YASUSHI TAMURA, YOSHINOBU KONDO, SHINOBU SATOH, OSAMU HASEGAWA, SOTOSHI KATO, YASUO YERAUCHI, Fujisawa, Japan, Chigasaki, Japan, Yokohama, Japan, Tokyo, Japan VEERAPPA A. KOTHIWALE, ANKUR BATRA, Belgaum, India There is a growing evidence showing a relationship between Insulin resistance and hypertension. Human as well as experimental studies have indicated the importance of reduced insulin sensitivity in etiopathogenesis of hypertension in some cases of essential hypertension. This study was performed to review the existing hypothesis that hypertension is an insulin resistant state irrespective of the diabetic status in Asian Indian adults. There is a scarcity of data probing this relationship in Asian Indian population. Hence, one year cross sectional study was conducted on 180 non diabetic adults of Asian Indian ethnicity who were grouped as normotensives(60), prehypertensives (60) and hypertensives (60) according to JNC VII classification. Insulin resistance was calculated as fasting Homeostatic Model Index (HOMA) using fasting plasma Insulin levels and was compared with blood pressure in all three groups with relevant statistical methods. We found that Normotensives had a mean HOMA index 2.17±0.66 while Prehypertensives and Hypertensives had a mean HOMA index 2.91±1.27 and 4.59±1.87 respectively. Scheffe test for intergroup variability and One Way ANOVA was performed for HOMA index which showed a highly significant correlation with p< 0.001. These results suggest that Insulin resistance is independently linked with blood pressure in non diabetic Asian Indian adults. We suggest lower intervention threshold and development of newer therapeutic strategies to combat insulin resistance irrespective of the diabetic status in such adults. The progression of diabetic microangiopathy is promoted by poor control of blood glucose and blood pressure. Macroangiopathy is also caused by poor blood glucose control and other factors such as lipid, blood pressure and lifestyle. Conceptually the progression of both types parallel one another in diabetes mellitus (DM), and retinopathy is reportedly a risk factor of cardiovascular disease (CVD). This study examined the associations of CVD and diabetic microangiopathy in patients with type 2 DM. Subjects were 1003 ambulatory patients with type 2 DM (578 males, 425 females). They were 63.7 ± 12.3 years old, suffering from diabetes for 136 ± 111.8 months, and were divided into two groups: a CVD (+) group of 387 patients showing ischemic ECG findings as abnormal Q, ST depression, and negative T or history of angina pectoris or myocardial infarction. The other CVD (-) group of 616 patients had none of the above findings. Retinopathy was graded into 4 stages: none, (N); mild or moderate non-proliferative, (MNP); severe nonproliferative, (SNP); and proliferative, (P). Nephropathy was classified into three Stages: 1, 2, and 3A or worse. Subjects were first screened for CVD, retinopathy, nephropathy, and clinical background, and then estimates of the extent of CVD, retinopathy and nephropathy were made. The progressive stages of retinopathy and nephropathy were associated with CVD. For the 4 stages of retinopathy CVD (+) frequencies were: 35%, 47%, 50%, and 57%, respectively. For CVD (-) they were 65%, 61%, 50%, and 44%. (p < 0.0001). For the 3 stages of nephropathy, the CVD (+) frequencies were 32%, 42%, and 60% respectively. For CVD (-) they were 68%, 58%, and 40%. The DM patients showed association of CVD with progressions of macro- and microangiopathies. However, some patients showed no association despite having progressive microangiopathy, suggesting the development and progression of CVD and microangiopathy were also affected by different illness-specific risk factors. Cardiovascular disease (CVD) is the leading cause of death in adults with type 1 diabetes(T1D), and the risk for CVD is particularly increased in young women with T1D. This study examined carotid intima-media thickness(cIMT) in the common carotid artery, a measure of atherosclerosis in premenopausal females between 14 and 46 years of age with T1D and without diabetes (non-DM). Study participants with T1D (n=32, age 27±11 years, duration 18±10 years) and non-DM controls (n=46, age 26±7 years) were enrolled in CVD risk factor studies at the Barbara Davis Center. cIMT was measured bilaterally via ultrasound, and the side with the maximum thickness was used in the analysis. Other measured risk factors included body mass index (BMI), systolic blood pressure (SBP), total cholesterol, and LDL. Correlations and partial correlations were examined by T1D status, followed by multivariable linear regression to evaluate the relationship between cIMT and T1D. T1D females had a higher mean cIMT than non-DM females (0.55±0.08 vs. 0.51±0.06, p=0.01), a higher BMI (p=0.01) and higher SBP (p=0.0004). In participants with T1D, cIMT was correlated with older age, higher BMI and higher SBP, whereas in non-DM participants cIMT was correlated with age and higher total and LDL-cholesterol. In multivariate linear regression models, mean cIMT remained significantly higher in young women with T1D when adjusting for BMI and LDL individually, but was attenuated (p=0.07) when adjusted for SBP. In a model adjusting for age, BMI, SBP, T1D, and LDL, the association between cIMT and both SBP and LDL differed based on diabetes status (p=0.004 for both interactions), with SBP only significantly related to cIMT among participants with T1D, and LDL only significantly associated with cIMT among non-DM participants. These findings suggest that risk factors for early development of atherosclerosis during the premenopausal years may differ between young women with T1D and similar aged non-DM women. 1435-P Comparison of Left Ventricular Filling Pressures between Male Patients With Type 2 Diabetes With Normal versus Low Total Testosterone Levels MATIAS TINETTI, JAVIER FARIAS, MARIANO FERRER, ADRIAN BARANCHUCK, Buenos Aires, Argentina, Ontario, ON, Canada The aims of this study were to compare in male patients with type 2 diabetes without structural heart disease, the left ventricular filling pressures (LVF) in those with normal and low total testosterone (LTT) levels Heart failure is a complication of diabetic patients and LVF is increased before symptoms appear. LTT mediated diastolic function abnormalities through regulation of peripheral hemodynamics. Male patients with type 2 diabetes have LTT in 30% of cases. The relationship between LTT levels in male diabetic patients and LVF is unknown We assessed diabetic patients (p) with tissue Doppler imaging for evaluation of left ventricular filling pressures by passive transmitral left ventricular inflow velocity to tissue Doppler imaging velocity of the lateral mitral annulus during passive filling (E/e’ ratio). Patients with history of heart failure, myocardiopathies, left ventricular hypertrophy, diastolic dysfunction (E/e´>15) and arrhytmias were excluded. We compared them depending on low (< 3,5 ng/ml, group A) or normal (> 3,5 ng/ml, group B) total testosterone levels. All patients were asymptomatic and without history of cardiovascular disease. Biochemical test and bioparametric results were measured. Data were analyzed using Mann Whitney U test and x2 test. A total of 148 male p were included. Mean age was 58 years (±5,8) and mean time of diabetes evolution 7 years (±3,1). Group A 47p (32%) and Group B 101p (68%). There was no difference between groups regarding age, time of diabetes evolution, hypertension, weight, heart rate, BMI or echocardiographic parameters .The E/e’ ratio in group A was 8,05 (±1,9) vs. group B 6,1 (±1,7) p < 0,0001. Patients with type 2 diabetes and LTT levels have higher E/e’ ratio, showing pre clinic increased left ventricular filling pressures vs diabetic patients with normal testosterone levels. This finding is independent of time of diabetes evolution, hypertension, or other echocardiographic parameters. ADA-Funded Research & 1438-P The Relationship of Age at Menarche and Menopause With Diabetes in Chinese Women GANG CHEN, JUNPING WEN, Fuzhou, China Context: Age at menarche and menopause were associated with cardiovascular disease (CVD), diabetes mellitus and osteoporosis in Caucasian women. However, the associations were largely unexplored in China. Objective: We assessed the relationship of age at menarche and menopause with CVD, diabetes and osteoporosis in Chinese women. Design and Setting: A cross-sectional, population-based study was conducted in Fujian, China from June 2011 to January 2012. For author disclosure information, see page 829. Guided Audio Tour poster A375 POSTERS LINDSEY M. DUCA, TALIA L. BROWN, RACHEL M. SIPPL, FRANZISKA BISHOP, DAVID MAAHS, PAUL WADWA, JANET K. SNELL-BERGEON, Aurora, CO Epidemiology/ Genetics 1437-P Risk Factors for Carotid Intima-Media Thickness Differ Between Young Women With and Without Type 1 Diabetes EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING Participants: A total of 5831 Chinese women aged 21-92years were entered into the investigation. Main Outcome Measures: We measured oral glucose tolerance test, 12lead resting ECG and calcaneus quantitative ultrasound. Results: Age at menarche was negatively correlated with diabetes risk (OR=0.95, 95%CI=0.91-0.99) and CVD risk (only among postmenopausal females, OR=0.95, 95%CI=0.91-0.99) and positively correlated with osteoporosis (OR=1.08, 95%CI=1.00-1.17) after adjustment for age. Menopause age was inversely associated with CVD risk (OR=0.97, 95%CI=0.95-0.99) and osteoporosis risk (OR=0.96, 95%CI=0.93-0.98), but not diabetes risk. Further adjustment for body mass index (BMI) and waist circumference (WC) eliminated associations of age at menarche with diabetes risk (OR=0.96, 95%CI=0.921.01) and CVD risk (OR=0.92, 95%CI=0.91-1.00). Conclusions: Early menarche seems to be associated with increased risk of diabetes and CVD, decreased risk of osteoporosis. Early menopause may increase the risk of CVD. Females who had age at menopause 50-54years had a lower osteoporosis risk than the reference. This relationship of age at menarche with diabetes and CVD appears to be mediated by BMI and WC. History of early menarche and menopause may help in the identification of women with increased risk of diabetes, CVD and osteoporosis. height and weight were used for the DRT. Dysglycemia was defined as A1C ≥ 5.7% or 6.0% and diabetes as A1C ≥ 6.5%. 1161 subjects had complete data for analysis with means for age and BMI of 50 yrs and 29 kg/m2. 31% were male. Prevalence of A1C ≥ 5.7%, ≥ 6.0% and ≥ 6.5% were 37%, 17% and 5%, respectively. Sensitivity (SENS), specificity (SPEC) and area under the curve (AUC) for detection of increasing levels of A1C are shown in Table 1. Table 1 A1C ≥ 5.7% A1C ≥ 6.0% A1C ≥ 6.5% Threshold SENS SPEC AUC SENS SPEC AUC SENS SPEC AUC SCOUT DS 50 AU .63 .72 .73 .79 .67 .81 .95 .62 .90 ADA DRT 5 .69 .64 .71 .85 .59 .78 .95 .54 .84 RCG 100 mg/dL .52 .67 .65 .59 .64 .67 .74 .62 .75 SCOUT DS and the ADA DRT had significantly greater AUC and SENS relative to RCG for detecting A1C-defined dysglycemia and diabetes. SCOUT DS had comparable AUC and SENS relative to the ADA DRT with significantly higher SPEC. Both noninvasive tests significantly outperformed RCG for diabetes screening with the added advantages of not requiring blood or causing pain. & 1441-P POSTERS Epidemiology/ Genetics 1439-P Use of Discounted Combination Oral Hypoglycemics Improve Other Cardiometabolic Risk Factors in a Community Health Center Population Capillary Glucose Testing after Oral Glucose Load: A Convenient Screening Test for Type 2 Diabetes and Prediabetes in Latino Adults JEFFREY D. SIMMONS, NNEAMAKA NWANKWO, CINDY VALIENTE, Miami Springs, FL At least 25.8 million people in the U.S. have diabetes (DM). Of these, 7 million are undiagnosed. About 79 million more have prediabetes (preDM). DM disproportionately affects the elderly, as well as certain ethnic groups. DM affects 11.8% of Hispanics, but only 7.1% of whites. Many at high risk are not screened, often due to poor access to care. We need a reliable tool for early diagnosis of DM and preDM. Subjects were recruited from among Latino men and women, age 45 and over, with no history of DM. After an overnight fast, subjects were given a standard 75 g oral glucose tolerance test (OGTT), with venous blood drawn prior to and 2 hours after glucose load. At 2 hours, a simultaneous capillary glucose test (CGT) was done, A capillary glucose value of > 140 mg/dL was considered a positive screen. Over 3 years, a total of 116 subjects were enrolled and completed the study. Subjects with abnormal glucose on OGTT (preDM or DM): 46 (39.7%) Previously undiagnosed DM: 12 (10.3%) PreDM: 34 (29.3%) Subjects with abnormal glucose on CGT (preDM or DM): 62 (53.4%) PETER R. BAGINSKY, MITCHELL BARNETT, Vallejo, CA Miami Beach Community Health Center serves over 1000 Type 2 diabetics, the majority of which are uninsured. The complexity of the diabetic medical regimen and its associated cardiometabolic risk factors create a tremendous burden on the patients and necessitate choosing among various therapies based on financial considerations. Over 12 months ago, combination sitagliptin-metformin became available at a discounted rate in our center. We hypothesized that a combination therapy would allow for the patients to afford other therapies and lower their entire cardiometabolic risk profile. We reviewed the records of our patients who had been treated with combination sitagliptin-metformin for at least 6 months and had measurements of body weight (lbs), systolic blood pressure (sBP), low density lipoprotein cholesterol (LDL), and glycosylated hemoglobin (A1c) before and after initiation. A student t-test for paired samples was used to compare both samples. After 6 months of combination oral hypoglycemic therapy, patients lost an average of 4.79lbs (37pts, range -20 to +7, p=0.000039), had a drop in sBP of 8mmHg (35pts, range -104 to +7, p=0.048), drop in LDL of 24mg/dl (28pts, range -92 to +23, p=0.0001) and drop in A1c of 1.2% (40pts, range -9.1 to +1, p=0.0038). Discounted combination oral hypoglycemics may allow for better reduction in global cardiometabolic risk in patients who must choose therapies based on financial considerations. Comparison of Random Capillary Glucose, the ADA Diabetes Risk Test and SCOUT DS for Diabetes Screening in At-Risk Populations Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of a post-load CGT of >140 mg/dL to detect preDM or DM (compared with OGTT): Sensitivity (95% CI): 84.8% (71.1% - 93.7%) Specificity (95% CI): 67.1% (54.9% - 77.9%) PPV (95% CI): 62.9% (49.7% - 74.8%) NPV (95% CI): 87.0% (75.1% - 94.6%) Our findings show the use of a single fingerstick CGT after a glucose load is a sensitive screen for preDM or DM. Of the 116 subjects, 46 (39.7%) were found to have previously undiagnosed DM or preDM. The CGT identified 39 (84.8%) of these individuals. Clearly this test, will miss a few with abnormal glucose; particularly those with isolated impaired fasting glucose. Nevertheless, it is a simple, low-cost and powerful screening tool. It will initially identify most individuals with preDM. This test has advantages for screening the underserved population. It requires only an oral glucose drink and a glucose meter. JOHN D. MAYNARD, ANDREA BARRACK, PAUL MURPHREE, PANAGIOTIS LATHOURIS, NIKOLAOS TENTOLOURIS, STAUROULA LONDOU, KOSTAS TZEMOS, BYRON OLSON, MARWOOD EDIGER, CAROLE PALEY, MANDY SWANEPOEL, RICHARD POPE, Albuquerque, NM, Baton Rouge, LA, Athens, Greece, Steeton, United Kingdom ATLANTIC DIP: Are the IADPSG Criteria for GDM Missing Women Who Would Previously have been Identified With GDM Using WHO Criteria? EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING Guided Audio Tour: Clinical Epidemiology—Diagnosis and Screening (Posters: 1440-P to 1447-P), see page 15. & 1440-P & 1442-P ADRIENNE M. HEEREY, LOUISE CARMODY, BREDA KIRWAN, FIDELMA P. DUNNE, MARIA EGAN, Galway, Ireland Screening at risk subjects for prediabetes and diabetes is an important step in prevention efforts. We examined the accuracy of random capillary glucose (RCG, common for mass screening) and two noninvasive screening methods, SCOUT DS and the ADA diabetes risk test (DRT) for detecting increasing levels of abnormal A1C. We pooled data from studies performed in the US, UK and Greece that shared methods and aims. A diabetes score was calculated from skin fluorescence measured on the left forearm with SCOUT DS. A finger prick was done to measure RCG and A1C. Age, sex, history of gestational diabetes, family history of diabetes, history of high blood pressure, physical activity, ATLANTIC DIP now uses IADPSG criteria (fasting glucose ≥ 5.1 mmol/L; 1 h ≥ 10 mmol/L and 2 h ≥8.5 mmol/L) to identify Gestational Diabetes Mellitus (GDM) having previously used WHO criteria for diagnosis (fasting gluscose ≥6.1 mmol/L and 2h glucose ≥ 7.8 mmol/L). Potential missed cases of GDM using the IADPSG criteria (i.e. with a 2 h glucose 7.8 to 8.5 mmol/L) and the impact on maternal and neonatal health has not yet been investigated. We included women from 2005 -2012 who had a 75g OGTT for GDM diagnosis. Women were either part of a universal screening programme (2007–2010) or selective screening. Maternal and neonatal complications for “WHO” GDM & For author disclosure information, see page 829. A376 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING prevalence of diabetes and prediabetes were 10.6% (men 12.7%, women 8.5%) and 19.3% (men 23.6%, women 15.2%). When HbA1C was included as a diagnostic test, prevalence of diabetes and prediabetes were increased to 12.7% (men 14.8%, women 10.5%) and 38.3% (men 40.7%, women 36.0%). Mean values of HbA1C were 5.5% (SE 0.0%) of normal glucose tolerance, 5.8% (SE 0.0%) of impaired fasting glucose, and 7.4% (SE 0.2%) of newly diagnosed diabetes, respectively. We concluded that using fasting glucose only can be underestimated to define diabetes and prediabetes. National standardization should be needed to use HbA1C as a diagnostic test of diabetes and prediabetes. women (i.e. with a 2h glucose 7.8-8.5mmol/l) were compared to women with normal OGTT (NGT). The Pearson Chi square test was used with a p value of ≤ 0.05 as significant. Of 4,398 women who had a 75g OGTT, 2,707 (62%) were diagnosed with NGT and 1,691 (38%) with GDM. 827 (19%) had GDM using both criteria; 695 (16%) with IADPSG criteria alone and 169 (3.8%) with WHO criteria alone. Rates of emergency Caesarean sections were significantly greater in WHO GDM women (20%) compared to NGT women (14%) (P<0.05) and WHO GDM women were more likely to develop polyhydramnios (2.6% v 0.8%)(P<0.05). Neonatal hypoglycaemia (2.3% v 0.7%) and congenital malformations (4.7% v 1.6%) were both significantly greater in offspring of WHO GDM women compared to NGT women (P<0.05). To conclude, less than 4% of women would not now be identified with GDM using IADPSG criteria but would previously be classified with GDM by WHO criteria. Maternal complication rates for these women and their offspring are greater compared to NGT women. Future prospective studies are necessary to ensure that the 2 h IADSPG threshold of >/=8.5 mmol/L is not now too high. & 1443-P Abnormal Glucose Tolerance in Women With Polycystic Ovary Syndrome (PCOS): Role of Sex Steroids and Obstructive Sleep Apnea KARLA A. TEMPLE, ESRA TASALI, BABAK MOKHLESI, HARRY WHITMORE, SYDEAKA WATSON, EVE VAN CAUTER, DAVID A. EHRMANN, Chicago, IL Obstructive sleep apnea (OSA) is a risk factor for cardiometabolic dysfunction that is highly prevalent in women with PCOS. We sought to examine the effects of sex steroids upon glucose tolerance and OSA prevalence and severity in women with and without PCOS. Following an overnight polysomnogram (PSG), 175 women (PCOS n=129; control n=46) (BMI (kg/m2): 38.6 + 0.6 vs 39.4 + 1.1, p=0.495; Age (yr): 28.2 + 0.5 vs 31.0 + 0.9, p=0.004) had a 2-h 75-g oral glucose tolerance test (OGTT): progesterone, total and free testosterone were measured at time 0; glucose, insulin, and C-Peptide were measured every 30 min for 2-h. All analyses were adjusted for age, BMI, and ethnicity-based diabetes risk. Nineteen (41%) control and 62 (48%) PCOS women had OSA (OR for OSA=2.4, CI 1.1-5.6; p=0.03) after controlling for age, BMI, and race risk. OSA was more severe in PCOS women as reflected by the mean apnea-hypopnea index (AHI) during the PSG (4.7 + 0.1 vs 1.7 + 0.2, p<0.001). Eleven (24%) control and 50 (39%) PCOS women had prediabetes (IFG or IGT) (p<0.01). Glucose tolerance was decreased by the presence of both PCOS (p<0.001) and OSA (p=0.002). Insulin levels and insulin secretion rates (ISR) during the OGTT were increased in PCOS women (p<0.001 for AUC). Fasting and 120-min ISR were increased in the presence of OSA (p=0.001 and p=0.022 respectively). Among women with PCOS, 2-h glucose levels were positively correlated with OSA severity (p=0.017) and negatively correlated with progesterone concentration (p=0.03); the correlation with testosterone concentration was not significant (p=0.07). In contrast, these relationships were not significant in controls (p=0.18, p=0.45, p=0.53 respectively). Conclusions: Compared to controls, women with PCOS have a higher prevalence of both OSA and prediabetes. Both severity of OSA and progesterone levels are predictive of two-hour glucose values during an OGTT in women with PCOS. Women with both PCOS and OSA are at greater risk for developing diabetes. Supported by: CDC & MARY RHEE, SANDRA L. JACKSON, DARIN E. OLSON, WENQIONG XUE, QI LONG, J. SONYA HAW, DIANA BARB, ARUN V. MOHAN, ANNE TOMOLO, PHYLLIS WATSON-WILLIAMS, LAWRENCE S. PHILLIPS, Atlanta, GA, Decatur, GA Since inpatient glucose levels are variable, their usefulness as a marker of diabetes risk has been questioned, but is not well understood. To determine potential predictive utility, we evaluated hospital glucose levels in 10,522 veterans using the VA Informatics and Computing Infrastructure (VINCI) database - in patients hospitalized between 2000-2009 for ≥3 days on medical/surgical services, with ≥1 primary care visit within 2 yr before and annually for 3 yr afterwards, and with no diagnosis of diabetes (ICD-9 code 250.xx or a diabetes drug) before or during hospitalization. 7,556 patients did not have diabetes (normal, NL) throughout, and 2,966 were diagnosed after discharge - 719 DM 1yr, 568 DM 2yr, 550 DM 3yr, and 1,129 DM 4-5yr. Patients had mean age 58.4 yr and BMI 33.8, and were 90% male, and 22% black. Using 3 hospital glucose values per patient (minimum, maximum, median) to offset variability in sample numbers, we examined sensitivity and specificity of glucose levels to identify patients diagnosed with DM 1-3 yr after discharge. A glucose level of 170 mg/dl (equivalent to the NL group 95th percentile) was insensitive but specificity was 95% - highly predictive of clinically diagnosed diabetes in the next 3 years. Conclusion: Although hospital glucose values reflect multiple factors other than insulin resistance and insulin secretion, levels above 169 mg/dl are highly specific for diabetes within 3 years post-discharge, and should trigger screening for diabetes after hospitalization. Supported by: NIH (P50-HD057796), (R01HL075079), (P60-DK020595), (UL1RR024999); Kovler Foundation & 1444-P Diabetes and Prediabetes are Largely Increased when HbA1C Is used as a Diagnostic Test JA YOUNG JEON, BU KYUNG KIM, SEUNG JIN HAN, KWAN-WOO LEE, DAE JUNG KIM, Suwon, Republic of Korea, Busan, Republic of Korea Due to the inconvenience of performing an oral glucose tolerance test, and day-to-day variability in glucose, HbA1C has now been recommended by the American Diabetes Association as a method to diagnose diabetes. Korean Diabetes Association also recommended HbA1C as a diagnostic test. We evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) only or both FPG and HbA1C. The data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2011 were analyzed. Among 5,811 subjects aged 30 years or older, 5,128 were selected after excluding the data of fasting time < 8hrs and/or the missing values of fasting glucose or HbA1C. Diabetes was defined as 1) FPG ≥126 mg/dL, 2) previous diagnosis by medical doctors, 3) current use of anti-diabetic medications, and/or 4) HbA1C ≥6.5%. Prediabetes was defined as 1) FPG of 100-125 mg/dL, and/or 2) HbA1C of 5.7-6.4%. When we used FPG only, ADA-Funded Research & 1446-P Inpatient Glucose Levels Predict Clinical Diabetes After Hospitalization For author disclosure information, see page 829. Guided Audio Tour poster A377 POSTERS Postpartum glycemic screening in women with history of gestational diabetes (GDM) identifies abnormal glucose after pregnancy and allows for early identification of Type 2 diabetes. Little is known about national patterns of post-partum screening in clinically and geographically diverse settings. Using claims data from an insurance database comprising 48 million members in all 50 states, we identified women aged 15-44 with GDM with one inpatient or 2 outpatient ICD-9 codes (648.8X) and continuous enrollment 310 days pre and 1 year post-delivery in 2002, 2004, 2007, or 2010. We identified screening type (75g oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), HbA1C) and timing (< 6, 6-12, and 12-52 weeks). Of the 11,463 women with GDM in the 4 years combined, 22% received any form of screening in the year post-partum. On logistic regression adjusted for race/ethnicity, age, geographic region, and number of pregnancies, older age (OR 1.23, 95% CI 1.02-1.48 for >=40 vs. 15-<30 yrs), Asian race/ethnicity (OR 1.75, 95% CI 1.52-2.02, vs. white), and geographic region were associated with any screening. Rates in the West were significantly higher than in all other regions and rates in the Midwest significantly lower. Over the 4 time periods, screening rates increased (OR 1.07, 95% CI 1.03-1.18 per period), as did use of the recommended 75g OGTT (OR 1.31, 95% CI 1.20-1.44 per period). However among those screened (N=2520), A1C alone was commonly used (36% of all tests), and represented 15% of testing at <12wks. Use of A1C was highest in women with black race/ethnicity (OR 1.47, 95% CI 1.042.09, vs. white) and in the Midwest and Northeast (ORs 1.66 and 1.66, 95% CIs 1.32-2.10 and 1.24-2.23, respectively, vs. West). In sum, type and timing of post-partum diabetes screening differ by geographic region, age, and race/ethnicity. Rates of screening and use of the recommended 75g OGTT have been increasing over time, however HbA1C is commonly used, even in the immediate post-partum period. Epidemiology/ Genetics EMMA M. EGGLESTON, ROBERT LECATES, FANG ZHANG, JAMES F. WHARAM, DENNIS ROSS-DEGNAN, EMILY OKEN, Boston, MA Supported by: HRB & 1445-P Variation in Post-Partum Glycemic Screening in Women With a History of Gestational Diabetes EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING HOSPITAL GLUCOSE mg/dL >= 100 110 120 130 140 141 150 160 170 180 190 200 however, the pathology is not well-known. We investigated that galectin-3 could be a predictor of worsening glucose tolerance. We measured serum Galectin-3 level of 81 participant received OGTT in 2005 and 2009. In 2005, the participants were NGT 46, IGT 30, DM 5. The mean serum galectin-3 level of all participants was 1732 pg/ml. Nine participants were worsening glucose tolerance (NGT to IGT, and IGT to DM), the mean serum galectin-3 level of these participants was 3721 pg/ ml, it was significantly higher than non-worsening group of 1537 pg/ml. The optimal cut-off level of galectin-3 to detect worsening glucose tolerance was 2400 pg/ml using ROC analysis (sensitivity 78%, specificity 80%). In a biphasic logistic analysis, galectin-3>2400 was a significant risk factor of worsening glucose tolerance, the odds ratio was 14.8 (P<0.005, 95%CI 2.42-90.0, adjusted by age, gender, BMI, FPG, I.I., HOMA-IR). Galectin-3 level positively correlated with high sensitive CPR (R=0.27, P<0.05). These results suggested that high serum galectin-3 level predicts worsening glucose tolerance. In conclusion, Galectin-3 is a good predictor of worsening glucose tolerance. DIABETES DIAGNOSIS WITHIN 3 YEARS AFTER HOSPITALIZATION SENSITIVITY SPECIFICITY 78.0% 36.1% 62.3% 54.5% 48.5% 68.5% 37.4% 78.5% 28.6% 85.0% 27.7% 85.4% 21.9% 89.4% 17.1% 92.7% 13.4% 94.8% 10.6% 96.3% 8.2% 97.3% 6.5% 98.0% Odds Ratio of risk factors worsening glucose tolerance Risk factors Odds Ratio P value Galectin-3>2400 14.8 <0.005 Age 1.04 0.57 Gender (male) 0.84 0.85 BMI 0.92 0.64 FPG 1.07 0.16 Insulingenic index 2.01 0.39 HOMA-IR 0.89 0.92 Supported by: U.S. Dept. of Veterans Affairs & 1447-P A Method of Diabetes Risk Assessment Based Solely on Information from a Nuclear Magnetic Resonance Spectrum of Plasma POSTERS Epidemiology/ Genetics JAMES OTVOS, THOMAS O’CONNELL, Raleigh, NC Risk of progression to Type 2 diabetes is currently assessed by fasting glucose, with concentrations 100-125 mg/dL defining a high-risk “prediabetes” condition. However, the risk of individual patients with prediabetes varies widely. To identify the highest-risk patients who would benefit the most from intervention, we developed a Diabetes Risk index (DRI) that uses only information derived from a single nuclear magnetic resonance (NMR) spectrum of a fasting plasma sample. This information includes glucose and lipoprotein subclass/size parameters previously linked to insulin resistance as well as novel metabolite information including the branchedchain amino acid, valine, and a unique NMR-based inflammatory marker that provides a global measure of protein glycoslyation. We used NMR spectra collected at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA) to develop the DRI score. The dataset consisted of 3185 participants, 280 of whom developed diabetes during 5 years of follow-up. The Figure presents the diabetes conversion rates of subjects within 6 glucose subgroups (dotted line), and those for subjects in the upper and lower quartile of DRI within each glucose stratum. As shown, the risk of developing diabetes at any given glucose level is substantially greater for DRI in Q4 vs Q1. It thus appears that a simple NMR-based diabetes risk score can effectively stratify risk without the need for additional clinical information. 95%CI 2.42-90.0 0.90-1.20 0.13-5.22 0.65-1.29 0.97-1.18 0.40-10.3 0.07-10.7 1449-P Mechanism of the Dawn Phenomenon in Patients With Type 2 Diabetes KEISHI YAMAUCHI, YUKA SATO, TORU AIZAWA, Matsumoto, Japan The Dawn phenomenon (DF) is an early-morning rise in blood glucose that occurs before or shortly after waking without nocturnal hypoglycemia. It can be troublesome for patients with diabetes. However, the definition of this condition is unclear. In the study, we analyzed mechanism of DF by dividing into before waking (3 a.m. to 6 a.m.) and after waking (6 a.m. to 8 a.m.) in inpatients of our hospital with type 2 diabetes. We measured plasma glucose concentration (PG) at 3 a.m., 6 a.m. and 8 a.m. (=fasting), fasting immunereactive insulin, others such as lipids and hormones. Those with insulin therapy or high fasting plasma glucose (>11mmol/L) were excluded. We defined that more than 5% of elevation of PG was the significant elevation, and the elevation between 3 a.m. and 8 a.m. was that DF is positive (DF+). Further we divided DF+ into a group starting of the elevation before waking (BW) and the other after waking (AW). DF+ was found in 39%. Difference of age between DF+ and DF negative (DF-) have that tendency, but is not significant. Although there were no differences of HOMA−IR nor HOMA−β between of DF+ and DF-, HOMA-IR of AW was notably higher than DF-’s and BW’s and HOMA−β of BW was significantly lower than DF-’s and AW’s. These results suggested that BW is related to insulin secretory ability and AW may be subject to influence from insulin resistance. In this study, we showed that BW and AW occur by a different mechanism, respectively and may be useful of measuring PG at 3 a.m., 6 a.m. and 8 a.m. for estimating the quality of DF. Selected data of the study All Number (male/female) Age HoMA-IR HOMA-β #, P 1448-P Galectin-3 Is a Good Predictor of Worsening Glucose Tolerance TSUYOSHI OHKURA, YOUHEI FUJIOKA, HIDEKI SHIOCHI, KEISUKE SUMI, NAOYA YAMAMOTO, KAZUHIKO MATSUZAWA, SHOICHIRO IZAWA, HIROKO OHKURA, MASAHIKO KATO, SHIN-ICHI TANIGUCHI, KAZUHIRO YAMAMOTO, Yonago, Japan DF- DF+ All BW AW 66 43 23 7 16 (45/21) (28/15) (17/6) (5/2) (12/4) 60.6±13.6 59.1±14.0 63.6±13.2 64.3±13.1 63.3±13.3 2.14±1.53 2.01±1.63# 2.13±1.33 1.30±0.88## 2.49±0.93 29.2±19.2 32.2±17.2* 22.7±16.3 10.1±3.9 28.2±15.9* Galectin-3 was reported as a predictor for prognosis of heart failure, Galectin-3 is a family of soluble beta-galactoside-binding lectin that play many important regulatory roles in inflammation. In diabetic patients, it was reported that serum galectin-3 level negatively correlated with HbA1c, & For author disclosure information, see page 829. A378 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING non-HLA SNPs in DAISY and found that PTPN22, UBASH3A, INS and IFIH1 were significantly associated with development of islet autoimmunity (IA) and/or progression from IA to diabetes. A total of 1607 non-Hispanic white DAISY children were now evaluated for these 30 non-HLA single nucleotide polymorphisms (SNPs) and thyroid peroxidase (TPO) antibody. Of those, 7% (n=109) had thyroid autoimmunity defined as positive TPO antibody during at least one study visit. In Cox PH models adjusting for HLA-DR3 genotype and family history of type 1 diabetes, GSDM (rs2290400), SH2B3 (rs3184504) and 2 UBASH3A SNPs (rs11203203 and rs9976767) were associated with thyroid autoimmunity (HR 1.36, 1.53, 1.44 and 1.43 respectively, all p < 0.03). PTPN22, CTLA4 and IFIH1 were not significantly associated with thyroid autoimmunity (HR 1.34, 1.10 and 0.8 respectively, p > 0.1), likely because of small sample size. Additional shared non-HLA genetic loci may play an important role in the early onset of autoimmune phenotypes in this cohort of young children with high-risk HLA markers for type 1 diabetes. 1450-P Serum Irisin Levels in New-Onset Type 2 Diabetes YEON-KYUNG CHOI, KWI-HYUN BAE, JI-YUN JEONG, JUNG-GUK KIM, IN-KYU LEE, KEUN-GYU PARK, HYUN-AE SEO, EUI-HYUN KIM, JAE-HAN JEON, Daegu, Republic of Korea Aims: Irisin has been identified as a novel myokine that drives brown-fatlike conversion of white adipose tissue. In this cross-sectional study, we investigated whether serum irisin levels are decreased in patients with type 2 diabetes (T2D) compared to control subjects with normal glucose tolerance (NGT), and assessed the association between serum irisin levels and various metabolic parameters. Methods: This population-based study included 104 subjects with NGT and 104 subjects with new-onset T2D. Serum irisin and adiponectin levels and metabolic parameters were measured. Multivariate logistic regression analysis was performed to assess the association between irisin levels and the development of T2D. Results: Serum irisin levels were significantly decreased in the newonset T2D group compared with the NGT control group (p =0.003). In a multivariable model adjusted for various metabolic parameters, increased irisin levels were associated with reduced odds (OR 0.64, 95% CI 0.47-0.88, p = 0.006) of prevalence of T2D. Furthermore, multiple regression analysis showed that 2 hour plasma glucose was an independent variable influencing serum irisin levels (p = 0.004). Conclusion: In the present study, we found that serum irisin levels were decreased in T2D patients and inversely associated with the development of T2D, suggesting that irisin may play a crucial role in glucose intolerance and T2D. Supported by: JDRF (11-2010-206) 1453-P Neck Circumference Correlates Better With Glucose Homeostasis than Waist or Waist-to-Hip Ratio 1451-P The Visceral Fat Accumulation Affects Plasma Free Amino Acid (PFAA) Profile and the Index Generated from PFAAs can Distinguish Visceral Obesity in Japanese Subjects KENJI NAGAO, TAKAYUKI TANAKA, YUKO ISHIZAKA, TORU MITUSHIMA, MIZUKI TANI, AKIKO TODA, EIICHI TODA, MINORU OKADA, HIROSHI MIYANO, HIROSHI YAMAMOTO, YASUSHI NOGUCHI, MINORU YAMAKADO, Kawasaki, Japan, Tokyo, Japan, Chiba, Japan Metabolic complications associated with obesity are prevailing among Japanese subjects. While visceral fat plays a pivotal role in development of an unfavorable metabolic and atherosclerosis risk, visceral fat accumulation is not always apparent by measuring BMI or waist circumference in Asians because of the physiological characteristics particular to those ethnicities. Thus, high-throughput determination of the amount of abdominal adipose tissue is needed. We have previously reported that PFAA levels were altered by accumulation of visceral fat, not by subcutaneous fat, in 1,449 healthy Japanese subjects whose visceral fat area (VFA) was determined using computed tomography imaging (Clinical Obesity 2012;2:29-40). The following four categories, which were defined based on the BMI and VFA values, were used: healthy subjects, HS (BMI<25 kg/m2; VFA<100 cm2); apparent obese subjects, AO (BMI≥25 kg/m2; VFA<100 cm2); non-apparent visceral obese subjects, NAVO (BMI<25 kg/m2; VFA≥100 cm2); and obese subjects, Obesity (BMI≥25 kg/m2; VFA≥100 cm2). In this study, we further analyzed these populations according to those four categories. A hierarchical cluster analysis using Ward’s method toward each category revealed that the formations of amino acid clusters were identical between NAVO and Obesity, while those of HS and AO were different, indicating not only absolute levels of amino acids but also relative concentrations among each amino acid were affected by the VFA accumulation. A PFAA index to identify high VFAs (≥100 cm2) was developed by multivariate logistic regression model. The ROC_AUC of the generated indices were 0.78 to 0.83, and the sensitivity to identify subjects with NAVO was much greater than that of the waist circumference (73% vs. 46%, respectively). These indices, thus, can be used as a predictor of elevated visceral obesity and a risk assessment tool for metabolic complications in Asian populations. Supported by: NIH/NIDCR (R01DE020111) 1454-P How Does Adoption of the IADPSG/ADA Guidelines for Diagnosis of Gestational Diabetes Affect Women’s Perceptions of Disease Severity? JOYCE W. TANG, KENZIE A. CAMERON, ALAN PEACEMAN, RONALD T. ACKERMANN, Chicago, IL Adoption of IADPSG/ADA Guidelines for diagnosis of gestational diabetes (GDM) (75g 2 hour glucose tolerance test (GTT)) increases the proportion of pregnant women diagnosed with mild disease, and may lead more women to question their diagnosis. Perceived misdiagnosis could affect likelihood of obtaining follow-up care and adoption of healthy behaviors. We conducted semi-structured phone interviews with women diagnosed with GDM within 1 year of their delivery. We recruited patients with positive GTT results from 4 obstetrics and 1 endocrinology clinic in Chicago, IL; 3 clinics used 2 hour GTT; 2 clinics used 1 hour + 3 hour GTT. Women rated their agreement (5 point scale) with: “I had a mild case of GDM” and “I don’t think I truly had GDM.” Women rated (4 point scale) their risk for recurrent GDM and DM2, and compared pre- and post-pregnancy diet and exercise habits (healthier/more active, no change, less healthy/less active). Receipt of postpartum GTT was self-reported. Chi-square tests were used to test potential associations. Of 124 eligible patients, 74 completed interviews (33 Caucasian, 34 Hispanic, and 7 African-American); mean age was 34; 70% were diagnosed 1452-P Association of Non-HLA SNPs With Thyroid Autoimmunity in Children at Increased Risk for Type 1 Diabetes ALEXANDRA R. FOUTS, FRAN DONG, RANDALL WONG, JILL M. NORRIS, MARIAN J. REWERS, ANDREA K. STECK, Aurora, CO While type 1 diabetes and autoimmune thyroid disease cluster in individuals and families, shared non-HLA genetic markers have not been consistently replicated except for PTPN22, CTLA4 and IFIH1. The Diabetes Autoimmunity Study in the Young (DAISY) prospectively follows children at increased risk for the development of type 1 diabetes. We have previously examined 30 ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A379 POSTERS BMI, fat%, WC and WHR are standard anthropometric measures mostly associated with prediabetes and other cardiometabolic conditions. However, the potential relative value of neck circumference (NC) is not well characterized. This analysis compares the relative utility of NC with standard anthropometric measures by comparing correlations with glucose homeostasis measures. A total of 1,206 overweight/obese Hispanic adults, aged 40-65 years free of diabetes were recruited. NC was measured below the larynx, perpendicular to the neck; other anthropometric measures were assessed following the NHANES protocol. Prediabetes was defined as fasting plasma glucose of 100-125 mg/dL, 2-h glucose tolerance after OGTT of 140-199 mg/dL and/or hemoglobin A1c of 5.7-6.4%. Correlations and logistic regression analyses were adjusted for age, gender, smoking status and physical activity. NC was positively correlated with BMI (r=0.62), WC (r=0.60), hip circumference (r=0.55), fat% (r=0.39) and WHR (r=0.21) (all p values <0.0001). Correlations with most glucose parameters tended to be similar or stronger for NC compared to WC and other anthropometric measures: 1-hr OGTT (r=0.19), 2-hr OGTT (r=0.13), fasting insulin (r=0.45), 30-minute insulin (r=0.28) and HOMA-IR (r=0.44) (all p values<0.01). However, fat% showed the largest correlations with fasting glucose (r=0.16). Individuals classified in the upper and middle tertiles of NC were more likely to have prediabetes (OR=2.81, 95% CI: 1.88-4.20 and OR=2.16, 95% CI: 1.58-2.94, respectively) compared with those in the lowest tertile; similar analyses on WHR showed weaker associations (OR=1.99 and OR=1.40, respectively). These preliminary results suggest that NC is an excellent alternative for assessing central adiposity. It was highly correlated with central adiposity, insulin resistance, and glucose abnormalities. In cases where WC measures are difficult or impossible to measure, NC may be the measure of choice. Epidemiology/ Genetics KAUMUDI JOSHIPURA, FRANCISCO MUÑOZ, CRISTINA PALACIOS, CYNTHIA M. PEREZ, San Juan, Puerto Rico EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING The subjects were 367 pregnant women with plasma glucose 1h after 50-g OGTT of ≥140 mg/dl at 24-28 weeks of gestation. The 100-g OGTT was performed as a diagnostic test 2-4 weeks after the screening test. HbA1c was done at same time. The mean HbA1c value in women with GDM was significantly higher than women without GDM(5.66 ± 0.32% compared to 5.27 ± 0.22%). The HbA1c cutoff value of ≥5.85% had sensitivity of 28.6% and specificity of 98.4% while an HbA1c cutoff value of ≤5.35% had sensitivity of 88.4% and specificity of 68.7% in diagnosing GDM. Using HbA1c as the initial test, if the level of HbA1c is ≥5.85%, then the woman can be labeled as having GDM. If HbA1c level is ≤5.35%, then she may be labeled as normal. For women with an HbA1c level lying between 5.35% and 5.85%, an OGTT should be performed to correctly identify women with GDM. Using this methodology 88.4% of the GDM cases would have been detected and only 1.6% of normal women would have been wrongly labeled as having GDM. Also, this methodology would have obviated an OGTT in 59.9% women in our study. HbA1c in combination with OGTT has usefulness for diagnosis of GDM in Korea and can obviate the need of OGTT in women in GDM. via 2 hour GTT; 59% were managed with diet alone. Most women perceived their case of GDM to be mild (82%); 23% believed they were misdiagnosed. No significant differences by diagnostic test modality emerged (p>0.9 for both). Women who agreed their diagnosis was mild or misdiagnosed were no less likely than those who disagreed to perceive moderate or high future risk for GDM and DM2 (p>0.6 for all), and were equally likely to obtain postpartum GTT (p>0.3 for both) and adopt improved health habits postpartum (p>0.2 for all). Most women felt they had a mild case of GDM; almost a quarter questioned their diagnosis. Those diagnosed under the IADPSG/ADA guidelines were no more likely to perceive their disease as mild or misdiagnosed. These beliefs did not impact future risk perceptions or health habits. 1455-P Glycated Hemoglobin and Incident Type 2 Diabetes in Singaporean Chinese Without Known Diabetes POSTERS Epidemiology/ Genetics MARK A. PEREIRA, ANDREW O. ODEGAARD, WOON-PUAY KOH, DANIEL STRAM, JIAN-MIN YUAN, MYRON D. GROSS, Minneapolis, MN, Singapore, Singapore, Los Angeles, CA, Pittsburgh, PA Studies are limited, especially in Asians, on glycated hemoglobin (HbA1c) and risk of incident type 2 diabetes (T2D). We examined HbA1c and incident T2D in the Singapore Chinese Health Study. A subset of 5,781 men and women aged 48-81 at the time of the blood draw (1999-2004) reported never having a diabetes diagnosis. Over 5.5 years of follow-up we observed 125 incident cases of T2D. Hazard ratios (HR) for incident T2D according to HbA1c percentage were estimated with Cox regression. Results are shown in the table. After adjustment in Model 1 for age, sex, dialect group, year of interview, and education, T2D hazard ratios increased strongly with increasing HbA1c values throughout the full HbA1c range. In Model 2, adjustment for body mass index, hypertension, cigarette smoking, and consumption of alcohol revealed similar results as Model 1. These findings suggest HbA1c is a strong independent predictor of incident T2D in South Chinese men and women. Risk for future T2D diagnosis increases considerably even well within the range of HbA1c thought to be ‘normal’ (<6.0%). Studies are needed to more fully examine HbA1c as a predictor of future T2D risk in Asian and other populations. 1457-P Utility of Elevated 1-h Glucose Values for Assessment of Pathogenesis of Type 2 Diabetes in Japanese Individuals YORIKO HEIANZA, YASUJI ARASE, SATORU KODAMA, SHIUN DONG HSIEH, KAZUYA FUJIHARA, SHIRO TANAKA, AKIKO SUZUKI, OSAMU HANYU, KAZUMI SAITO, HITOSHI SHIMANO, SHIGEKO HARA, HIROHITO SONE, Tsukuba, Ibaraki, Japan, Tokyo, Japan, Mito, Japan, Kyoto, Japan, Niigata, Japan It has not been fully clarified how well adding data on elevated 1-h glucose values during an oral glucose tolerance test (OGTT) in addition to fasting plasma glucose (FPG) and 2-h plasma glucose (PG) values would contribute to understanding the relationship between the two most distinctive factors in the pathogenesis of type 2 diabetes (T2DM), which are insulin sensitivity and insulin secretion, in Asian individuals who are not predominantly overweight or obese. To clarify this issue, we investigated 1503 Japanese individuals without a history of treatment of diabetes. Participants were categorized into 5 groups according to glycemic status using WHO criteria ((1) normal glucose tolerance (NGT) with 1-h PG <155 mg/dL, (2) NGT with ≥155 mg/ dL, (3) impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) with 1-h PG <155 mg/dL, (4) IGT/IFG with ≥155 mg/dL or (5) T2DM). Differences in whole body insulin sensitivity (Matsuda index), early insulin secretion (insulinogenic index, IGI) and β-cell function (disposition index, DI) during the OGTT were evaluated across the glycemic categories. Regardless of having NGT or IGT/IFG, those with elevated 1-h PG values had a markedly decreased IGI. Compared to individuals with 1-h PG <155 mg/dL, the Matsuda index and DI were lower in individuals with 1-h PG ≥155 mg/dL among both the NGT or IGT/IFG groups. The DI of NGT with 1-h ≥155 mg/dL or IGT/IFG with ≥155 mg/dL did not greatly differ from that in T2DM. Introducing assessment using 1-h PG ≥155 mg/dL values into the current WHO criteria contributed to identifying individuals with a reduced early insulin response to oral glucose and those with beta cells with reduced ability to compensate for insulin resistance in Japanese individuals. These results would assist clinicians in finding patients whose insulin secretion is markedly low and in formulating an optimal approach to treatment to prevent a further progressive loss of beta-cell function. Supported by: NIH (R01CA55069), (R35CA53890), (R01CA80205) 1458-P Glucose Absorption Patterns Differ in Men and Women With Impaired Glucose Regulation KRISTINE FÆRCH, GIOVANNI PACINI, JOHN J. NOLAN, ANDREA TURA, DORTE VISTISEN, Gentofte, Denmark, Padova, Italy 1456-P The Usefulness of HbA1c for Diagnosis of Gestational Diabetes Mellitus in Korea The oral glucose tolerance test (OGTT) is often used to determine glucose intolerance, insulin resistance and beta cell dysfunction in populations at risk. We examined whether glucose absorption patterns after an OGTT differed between men and women with normal and impaired glucose regulation. Moreover, we explored the relationship of glucose absorption with body height because short and tall individuals may respond differently to a fixed amount of oral glucose. Different aspects of glucose absorption (total absorption, peak absorption, time to peak, and half-life of glucose in the gut) were estimated from 12-point 3-hour OGTTs in 66 middle-aged men and women with normal glucose tolerance (NGT, n=20), isolated impaired fasting glucose (i-IFG, n=18) and isolated impaired glucose tolerance (i-IGT, n=28). We found that during a standard 75 g OGTT: 1) individuals with i-IGT, particularly women, had lower total glucose absorption than NGT individuals (Fig 1A-B, P=0.003) and slower glucose absorption than i-IFG individuals KIWON KIM, YEO JOO KIM, HYEONG KYU PARK, JEONG RAN BYUN, SANG JIN KIM, Cheonan, Republic of Korea Gestational diabetes mellitus (GDM) was defined as a carbohydrate intolerance of varying severity with onset or first recognition during pregnancy, irrespective of glycemic status after delivery. Current screening for and diagnosis of GDM use oral glucose tolerance test(OGTT), based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) statement. However, it is a relatively complicated procedure and is associated with high cost. The adoption of easier strategies that do not require fasting or more than a single blood draw could help to diagnose GDM easy and to increase the rate of GDM testing. We investigated the usefulness of HbA1c for diagnosis of GDM. & For author disclosure information, see page 829. A380 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING (Fig 1A, P=0.002); 2) individuals with i-IFG had earlier peak of glucose absorption than NGT individuals (Fig 1A, P=0.013); and 3) glucose was more rapidly absorbed in taller compared with shorter individuals (P for linear relationship<0.001). Glucose absorption during a 75 g OGTT is disturbed in individuals with impaired glucose regulation, and in particularly in women, which may have implications for the interpretation of OGTT results. sampled intravenous glucose tolerance test. A total of 115 participants developed diabetes. ALT increased the C statistic of a multiple logistic regression model that had age, sex, ethnicity, and impaired glucose tolerance as covariates (0.780 vs. 0.802, p <0.001) and of a separate model that also included waist, SI, and AIR (0.840 vs. 0.851, p = 0.030). In this last model, ALT correctly reclassified a fifth of individuals with moderate and strong diabetic risks with a net reclassification improvement of 0.135 ± 0.039 (p = 0.005) and an integrated discrimination improvement of 0.022 ± 0.006 (p <0.001) (Table). In summary, ALT is useful for classifying individuals at risk of future diabetes independently of other risk factors. Table. Predicted and observed risks of incident diabetes in models with and without ALT Model 1 plus ALT Model 1 <1% 1 - 4% >4% % yearly risk yearly risk yearly risk Reclassified <1% yearly risk Total (%) 230 (94.9%) 15 (6.1%) — 6.1% Observed 0.4 1.3 — — yearly risk 1 - 4% yearly risk Total (%) 57 (22.1%) 185 (71.7%) 16 (6.2%) 28.3% Observed 0 2.1 9.6 yearly risk >4% yearly risk Total (%) — 19 (10.6%) 160 (89.4%) 10.6% Observed — 4.0 7.8 yearly risk 1459-P Relationship between Cadmium and Pre-Diabetes among U.S. Adults in NHANES AMISHA WALLIA, SYLVIA BADON, NORRINA ALLEN, MALEK EL MUAYED, Chicago, IL Prior epidemiologic and experimental studies suggest a potential relationship between cadmium exposure (Cd), an environmental pollutant, and dysglycemia. We evaluated the relationship between urinary Cd, a marker of exposure, and pre-diabetes (pre-DM) in participants of the crosssectional NHANES (National Health and Nutrition Examination Survey) study from 2005-2010. Participants were excluded if they were < 40 years old or were missing data. Pre-DM was defined as 2 of the following: A1c > 5.7% & < 6.5%, 2 hour OGTT glucose >140 & < 200 mg/dL, FPG > 100 & < 126 mg/ dL. We used restricted quadratic spline models to describe the non-linear association between urinary Cd and pre-diabetes [adjusted for age, race/ ethnicity, gender, BMI, education, survey years and smoking, a major source of Cd]. Mean urinary Cd was 0.40 µg/g creatinine (n=1,292). Higher Cd levels were associated with increasing odds of pre-DM (Fig). Compared with a Cd level of 0.1 ug/g (10 th percentile), a level of 1.0 ug/g (90 th percentile) had an OR of 2.13 (1.66-2.74) of having pre-DM. Smokers had higher Cd levels (0.56 ug/g vs 0.32 ug/g for ever-smokers and never-smokers respectively); however, the relationship between Cd exposure and pre-DM was consistent among smokers and non-smokers separately. In conclusion, there appears to be significant non-linear unimodal relationship between urinary Cd levels and odds of pre-DM. Further studies examining this relationship are warranted. Figure: Odds ratios for pre-DM (adj.) SANDRA L. JACKSON, DARIN E. OLSON, K.M. VENKAT NARAYAN, JOSEPH LIPSCOMB, QI LONG, PETER WILSON, JENNIFER MICHAELS, RINCY VARUGHESE, MARY RHEE, SONYA HAW, ARUN V. MOHAN, PHYLLIS WATSON-WILLIAMS, ANNE TOMOLO, DIANA BARB, LAWRENCE S. PHILLIPS, Atlanta, GA, Decatur, GA Diabetes prevention and care are limited by lack of screening. Screening with a 50g oral glucose challenge test (GCT), with measurement of plasma or capillary glucose 1 hour later, at any time, regardless of meal status - similar to screening for gestational diabetes - has been shown to be accurate, convenient, and cost-effective in volunteer subjects. We hypothesized that the GCT would also be useful in high risk patients. In a VA primary care clinic, subjects with BMI >25, age >45, or other risk factors had measurement of A1c, plasma and capillary random glucose (RPG and RCG), and plasma and capillary GCT (GCTpl and GCTcap). At a second visit, they had a diagnostic 75g OGTT. 1440 subjects had mean age 57 years and BMI 30.4, 94% were men, and 74% were black. By OGTT criteria, diabetes was present in 10% and high-risk prediabetes (IGT and/or IFG with glucose 110-125 mg/dl) in 22%. The GCTpl provided areas under receiver-operating characteristic curves (AUC) of 0.84, 0.76, and 0.70 for detection of diabetes, dysglycemia (diabetes or high-risk prediabetes), and high-risk prediabetes, respectively. GCTcap performed similarly, with AUCs of 0.82, 0.74, and 0.69 (all p=ns vs. GCTpl). In 958 patients with complete screening data, GCTpl and GCTcap were significantly more accurate than A1c, RCG, and RPG for detection of diabetes or dysglycemia (all p<0.05). Conclusions: Primary care patients with BMI >25, age >45, or other risk factors have a high prevalence of previously unrecognized diabetes and high-risk prediabetes - 32% in this study. GCT screening with measurement of plasma or capillary glucose 1 hour after a 50g glucose load, followed, if abnormal, by an OGTT, would be convenient it could be done opportunistically, during office visits - and would be more accurate than random glucose or A1c for identifying these problems. Widespread use of GCT screening could improve management by permitting early initiation of therapy aimed to prevent or delay the development of diabetes and its complications. 1460-P Alanine Aminotransferase Has Discriminatory Value for Detecting Individuals at Increased Risk of Diabetes: The Insulin Resistance Atherosclerosis Study (IRAS) CARLOS LORENZO, ANTHONY J. HANLEY, LYNNE E. WAGENKNECHT, MARIAN J. REWERS, STEVEN M. HAFFNER, San Antonio, TX, Toronto, ON, Canada, WinstonSalem, NC, Aurora, CO Supported by: U.S. Dept. of Veterans Affairs A marker of non-alcoholic fatty liver disease, alanine aminotransferase (ALT) is a known predictor of incident diabetes in Cox or logistic regression models. However, it is not known whether ALT adds discriminatory value to other diabetic risk factors. Therefore, we examined the ability of ALT to reclassify high-risk participants in the IRAS (n = 724; age, 40 - 69 years; median follow-up, 5.2 years). We excluded participants with lipid-lowering medications, excessive alcohol intake, and ALT >100 U/L. Insulin sensitivity index (SI) and acute insulin secretion (AIR) were measured by the frequently ADA-Funded Research & 1462-P The Relative Associations of β-Cell Function and Insulin Resistance With Glycemic Status in Asian Indians: The MASALA Study UNJALI P. GUJRAL, K.M. VENKAT NARAYAN, ALKA M. KANAYA, Atlanta, GA, San Francisco, CA Asian Indians are at high risk for type 2 diabetes mellitus (T2DM) at lower BMI which has raised speculation about innate susceptibility to For author disclosure information, see page 829. Guided Audio Tour poster A381 POSTERS 1461-P Glucose Challenge Test Screening for Diabetes and Dysglycemia in a High-Risk Primary Care Population Epidemiology/ Genetics Supported by: NHLBI; NCRR EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING the prevalence of anti GAD antibody and to characterize the phenotype of Egyptian patients with adult-onset, clinically diagnosed T2DM attending at The NIDE Cairo Egypt.A total of 500 Egyptian patients clinically diagnosed as T2DM and treated with insulin were studied.The inclusion criteria included: diagnosis of T2DM at age of ≥35 years, the lack of a requirement for insulin at least 6 months after the diagnosis of T2DM and age at recruitment < 70 years. Anthropometric and clinical data were compared amongst patients with or without autoantibodies. Beside routine investigations, both C peptide level & presence of glutamic acid decarboxylase antibodies were also assessed in these patients.Out of the total of 500 patients, GADA were found in 159 (31.8%). Age at diagnosis of DM, FPG and LDL & C peptide level were significantly higher among patients without GADA while among those with GADA the frequency of female sex was significantly higher. The female sex & low C peptide level were predictors of presence of GADA among this group of patients.We can conclude that the prevalence of GADA ( as a marker of autoimmune diabetes) among Egyptian insulin treating patients with adultonset, clinically diagnosed T2DM is high (31.8%). The clinical phenotype may not help to characterize these patients & the determination of GADA in particularly in females & those with low C peptide level represents the best tool for a correct classification and a necessary prerequisite for a correct therapeutic appraisal. β-cell dysfunction in addition to known insulin resistance. We assessed the relative associations of β-cell function and insulin resistance with glycemic status in a cohort (n=150) of Asian Indians in the United States. After an overnight fast, a 5-sample oral glucose tolerance test (OGTT) was completed. Normoglycemia (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and T2DM were defined by ADA criteria. The Matsuda Index (ISIM) and the Disposition Index (DI0) were used to measure insulin sensitivity and β-cell function, respectively. After 2.2 years of follow-up, participants had a 2-sample OGTT and HOMA-IR and HOMA-β were measured. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemic states. Mean age was 57.2±8.1 years, and mean BMI was 26.1± 4.6 kg/m2. Compared to NGT, after controlling for age, sex, BMI, visceral fat, family history of T2DM, hypertension, and smoking status, both log ISIM and log DI0 were significantly associated with prediabetes (OR 0.51, 95% CI: 0.27, 0.95) and (OR 0.22, 95% CI: 0.09, 0.58) and T2DM (OR 0.35, 95% CI: 0.15, 0.87) and (OR 0.003, 95% CI: 0.0001, 0.03), respectively. At follow-up, incidence rates were: NGT to IGT; 82.0 per 1,000 p/y; to IFG; 8.4 per 1,000 p/y, to T2DM; 8.6 per 1,000p/y; IGT to T2DM; 55.0 per 1,000 p/y; IFG to T2DM; 64.0 per 1,000 p/y. Both the change in HOMA-IR (OR 2.49, 95% CI: 1.57, 5.26) and HOMA-β (OR 0.32, 95% CI: 0.13, 0.77) were significantly associated with incident glycemic progression from NGT to IFG, IGT, or T2DM or from IFG or IGT to T2DM. Both insulin resistance and β-cell are associated with prediabetes and T2DM. The independent associations of both of these factors after adjusting for visceral fat indicates an innate susceptibility in Asian Indians for T2DM development. Supported by: National Institute of Diabetes & Endocrinology (Egypt) 1465-P Serum TSH Level Is Associated With Islet Beta Cell Function in Type 2 Diabetic Patients DAN DAN ZHANG, FANG LIU, WEI LU, HAO YONG YU, WEIPING JIA, Shanghai, China Objective: This study was to investigate the characteristics of serum supersensitive thyroid-stimulating hormone (sTSH) level and its relationship with pancreatic beta cell function in Type 2 diabete mellitus (T2DM) patients. Methods: A total of 1804 patients were enrolled in this cross-sectional study, including 1328 T2DM patients and 476 Non-diabetic controls, and they were divided into quartiles with respecting to their sTSH levels. FT3, FT4, and TSH were measured with chemiluminescent microparticle immunoassay. The clinical characteristics and biochemical indexes including the fasting and postprandial C-peptide levels (2h Cp) , their interpolation (ΔCp) and their relationship with TSH were analyzed. Results: FT3 and FT4 levels of diabetic patients were significantly higher than that of controls (both P <0.05), but the TSH level of T2DM patients was significantly lower than that of controls [(2.34±3.73 vs 4.00±9.70) mIU/L, P=0.018]. In diabetic population, TSH level in females was significantly higher than that of males [(2.73±3.79 vs 2.01±3.65) mIU/L, P=0.001], meanwhile, FT3 and FT4 level in females was lower than that of males (P=0.000, P=0.037). There were significant differences in body mass index (BMI) and triglyceride (TG) among TSH quartiles (all P<0.05). The levels of fasting C-p, 2h Cp, and ΔCP in the fourth quartiles was significantly higher than other three TSH quartiles (all P<0.01). However, HbA1c and GA in the fourth quartiles was significantly lower than other three quartiles (all P<0.01). Spearman correlation analysis showed that serum TSH level was positively correlated with 0’CP, 120’CP, ΔCP and gender, but was negatively correlated with HbA1c and GA ( all P<0.01). Multiple stepwise regression analysis further revealed that gender and ΔCP were independent associated factors of sTSH levels (all P<0.01). Conclusions: There is gender difference of serum TSH level, and high serum TSH level may hint increasing beta cell function in T2DM patients. 1463-P POSTERS Epidemiology/ Genetics Supported by: NIH (K23HL080026); AHA (0855069F) Altered Fatty Acid Metabolism in Healthy First Degree Male Relatives of 2DM Patients JOZSEF PAUER, BARBARA BUDAY, BOTOND LITERATI-NAGY, MARTA VITAI, LASZLO KORANYI, Balatonfured, Hungary The epidemic of obesity is associated with multiplication of prediabetic patients. The first degree relatives of 2DM patients have a life time risk for development of diabetes. As genom studies have not identified 2DM genes with strong predictive values, the need for a diagnostic procedure is essential for identification of those with high risk of 2DM. Our aim was to determine metabolic alterations in healthy men with (DR: n= 14) or without (H: n= 14) first degree 2DM relatives. Volunteers with normal glucose tolerance were adjusted according to age and BMI, insulin resistance was determined with hyperinsulinemic-normoglycemic clamps and β-sejt function by iv glucose tolerance test. Fasting glucose, insulin and FFA values were not different among the groups, but in the 60 th min, at the end of ivGTT glucose levels were higher (H:5.8 ± 1,5, vs. DR: 7,2 ± 1,4 mmol/l, p<0.05), the injected glucose did not suppressed FFA levels ( H: 0,17 ± 0,1 vs DR:0,36 ± 0,2 mmol/l,p<0.001) and first phase insulin secretion (AIR: acut insulin respose) was decreased in DR group (H:104±63 vs DR:59 ± 33; p<0.01). There were no differences among the groups in total body-, muscle tissue- , and fat tissue glucose disposal, leptin and resistin levels, but the adiponectin levels were significantly lower in DR group (H: 5,28±2,3 vs. GD:2,86 ± 1,7 mg/ml, p<0.001) and the FFA/adiponectin ratios were higher (H: 0,10±0,08 vs GD: 0,29± 0.2, p<0.01). In the DR group the HDL cholesterol levels were lower ( H:1.5±0,4 vs GD: 0,97± 0,2 mmol/l,p<0.002) and the lipid profile was atherogen with less small density and more high density LDL cholesterol fractions. In conclusion the impairment of insulin secretion and fatty acid metabolism are the earliest sign of diabetes risk in men with first degree 2DM relatives, prior to the manifestation of insulin resistance and glucose intolerance. The measurement of FFA/ adiponectin ratio could be a simple parameter to screen adult male relatives of diabetic patients for identification of genetic risk of diabetes. Supported by: NSFC (81070650) 1466-P A Chinese Risk Score Model for Identifying Abnormal Glucose Tolerance Without Oral Glucose Tolerance Test QI FU, MIN SUN, ZHIXIAO WANG, MENGDIE CAO, ZHENXIN ZHU, WEI TANG, MEI ZHANG, YU DUAN, WEI HE, TAO YANG, Nanjing, China 1464-P Objective: To develop a risk score model for identifing abnormal gulocse tolerance (AGT) based on routine clinical information without oral glucose tolerance tests (OGTT) in the Chinese population, and minimize the number of subjects needing further OGTT. Research design and methods: β coefficients from multivariable stepwise logistic regression in the derivation cohort (7953 participants without known diabetes of a community survey) were used to develop the risk score models. The performance of the risk score models was verified in the validation cohort (1455 subjects without known diabetes of another survey). All subjects had completed questionnaires, physical examination and OGTT. Performances of the risk score models were compared by using receiver operating characteristic (ROC) curves. Results: Pilot Study: The Prevalence of Positive Anti-GAD Antibodies Among Egyptian Insulin-Treated T2DM Diabetic Subjects at the National Institute of Diabetes and Endocrinology (NIDE) Cairo, Egypt IBRAHIM EL EBRASHY, A. BASSYOUNI, G. SALAM, S.N. AMAM, A. ABDELLA, A. MAHFOUZ, G. HUSSIEN, Cairo, Egypt Several studies have been performed in order to evaluate the prevalence of autoimmunity to β-cells in patients with adult onset diabetes and have been based on screening for ICA and/or GADA. In these studies, the prevalence of autoimmune diabetes ranged from 8 to 45%, according to different populations and selection criteria. The aim of our study was to evaluate & For author disclosure information, see page 829. A382 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING (58,605/95,529; 61.3%) despite having an HbA1c≥7%. Of the 36,924/95,529 (38.7%) patients who modified therapy, 13,031/36,924 (35.3%) added ≥1 drug, 11,483/36,924 (31.1%) switched drugs and 12,410/36,924 (33.6%) reduced the number of drugs taken. Adherence to ADA guidelines on HbA1c testing frequency and therapy modification was poor in this study population of US T2DM patients. Two risk score models for screening AGT were developed. The simple model used non-invasive risk factors, and the full model contained additional variables obtainable by invasive laboratory tests (consisting of age, height, waist, systolic blood pressure, pulse, hypertesion, family history of DM, fasting blood glucose, triglyceride/high density lipoprotein cholesterol). The area under curve (AUC) of simple model was similar to fasting blood glucose (FBG) and glycated hemoglobin (HbA1c). The full model has the largest AUC (0.799 [0.789-0.809] and 0.730 [0.702-0.758], P <0.001 compared with simple model, FBG, and HbA1c) in both derivation and validation cohorts. At a cut-off point of 80, the sensitivity, specificity, and percentage that needed subsequent OGTT were 75.97, 67.56 and 48.38%, respectively. Conclusions: We developed a risk score model for screening AGT based on routine clinical information. It could effectively identify high risk population of AGT and remarkably reduce the number of subjects requiring OGTT. Supported by: Chinese Society of Endocrinology 1467-P Adiponectin Binds to C1q in Human Serum, and C1q-Adiponectin/ Total Adiponectin Ratio Correlates With Coronary Artery Disease in Japanese Type 2 Diabetes HIRONORI KOBAYASHI, AYUMU HIRATA, KEN KISHIDA, HIDEAKI NAKATSUJI, SHIGEO TAKAHASHI, HIDEAKI TANAKA, SUGURU AKAMATSU, KIYONORI KATSURAGI, TOHRU FUNAHASHI, IICHIRO SHIMOMURA, Tokushima, Japan, Osaka, Japan, Tokyo, Japan Adiponectin (APN) is produced abundantly in adipose tissue, and its circulating level is decreased in subjects with excess intra-abdominal fat. Previously, several studies reported that APN binds to some molecules. However, the precise forms of APN in human blood have not been fully understood. The aim of this study is (1) to determine whether APN binds to complement C1q, (2) to develop the specific enzyme-linked immunosorbent assay (ELISA) system for measuring C1q-APN complex, and (3) to determine the clinical significance between C1q-APN complex and coronary artery disease (CAD) with Japanese type 2 diabetes mellitus (T2DM) patients. The direct interaction between adiponectin and C1q was detected in human serum by co-immunoprecipitation. We developed the specific ELISA system for measuring C1q-APN complex in human serum. Serial dilution of the C1q-APN complex was used to generate standard curve (R2=0.9998). Good linearity was observed with the diluted human serum. The intra- and intercoefficients of validation (CV) were below 4.6% and 6.7%, respectively. By using this ELISA system, we investigated the clinical significance of C1q-APN complex in T2DM patients diagnosed with CAD. Serum levels of C1q-APN/Total-APN ratio were higher in patients diagnosed with CAD (10.47±0.59, mean±SEM, n=54) than those without CAD (8.88±0.60, n=53, p=0.0482). Age- and sex-adjusted logistic regression analysis identified serum C1q-APN/Total-APN ratio and hypertension as significant and independent determinants of CAD. A high serum C1q-APN/Total-APN ratio was associated with 3.965-fold increase in CAD prevalence. These results indicated that C1q-binding APN complex exists in human serum. High serum C1q-APN/Total-APN ratio correlated with CAD in T2DM patients. This study suggested that measurement of C1q-APN complex may be a useful biomarker to evaluate the pathogenesis of CAD in T2DM patients. 1469-P Utility of Hemoglobin A1c for Predicting New-Onset Diabetes in Chinese Adults Supported by: Grant-in-Aid for Scientific Research on Innovative Areas 1470-P 1468-P Glycosylated Haemoglobin Level Predicts Incidence of Heart Failure Hospitalization Independently of Cardiorenal Functions or Prevalence of Cardiovascular Diseases in Patients With Advanced Diabetes Adherence to ADA HbA1c Testing Frequency and Antidiabetic Therapy Guidelines: Real-World Patient Data JEAN F. LIAN, YUANJIE LIANG, Princeton, NJ The 2009 ADA guidelines recommend HbA1c testing every 3 months and intensification of antidiabetic therapy for type 2 diabetes (T2DM) patients with HbA1c≥7%. This retrospective study evaluated adherence to these guidelines in the US. Data from healthcare claims (2009-2011) were evaluated for patients ≥18 years with ≥2 T2DM diagnoses (ICD-9CM codes 250.x0, 250.x2) and an initial HbA1c≥7%. An HbA1c test performed 3 months (+15 days) after a previous HbA1c of ≥7% was considered adherent. An addition to or switch in therapy within 30 (+15) days of an HbA1c of ≥7% was considered adherent, with the assumption that HbA1c testing frequency was adherent. Only patients with continuous enrolment for one year after their initial HbA1c test were evaluated for adherence to testing frequency. A total of 67,105/82,675 (81.2%) of all patients were not tested for HbA1c values at the recommended frequency even once a year (Fig. 1). Adherence decreased with subsequent tests. Only 4.0% of patients adhered to testing frequency over one year. Most patients did not modify their existing therapy ADA-Funded Research & ICHIRO KISHIMOTO, HISASHI MAKINO, YOKO OHATA, TAMIKO TAMANAHA, MAYU TOCHIYA, AYAKO TANAKA, RYO KOEZUKA, Suita, Japan Growing evidence indicates that dysglycemia is a risk factor for cardiovascular disease, but the relationship between diabetes control and the risk of heart failure (HF) remains poorly understood. In addition, if diabetes control is associated with HF events independent of other comorbidities such as hypertension, chronic kidney disease or coronary heart diseases (CHD) has not been well determined. To examine the direct impact of diabetes control on incidence of heart failure, we evaluated the association between baseline HbA1c and risk of hospitalization for congestive HF in diabetes patients taken cardiac/renal functions and prevalent comobidities into account. In six hundreds asymptomatic patients with type 2 diabetes, who were at high-risk for HF, the effect of baseline HbA1c level on the hospitalization for HF was analyzed in a time-to-event manner. Hazard ratios were calculated using a Cox-proportional hazards model with adjustments of cardiorenal functional parameters and prevalence of cardiovascular diseases For author disclosure information, see page 829. Guided Audio Tour poster A383 POSTERS Although many different cutoff levels of hemoglobin A1c (A1C) in diagnosing diabetes have been suggested in the past, the usefulness of different A1C cutoffs for predicting diabetes in the Chinese population remained unclear. This study, a follow-up to the two Shanghai Diabetes studies conducted from 2010 to 2012, aimed to evaluate the effectiveness of A1C in predicting new-onset diabetes in Chinese adults. All subjects underwent a 75-g oral glucose tolerance test and HbA1c was assessed at baseline and followup. A total of 2747 non-diabetic subjects (A1c < 6.5%) aged 20-75 years old were enrolled. Exclusion criteria included pregnancy, severe kidney damage (eGFR<30 ml·min-1·1.73m-2), anemia (hemoglobin <120g/L in men and <110g/L in women), serum hepatitis B surface antigen positive, anti-hepatitis C antibody positive and abnormal serum alanine aminotransferase level (> 69 IU/L). Among them, a total of 206 individuals developed diabetes during the average 8-year follow-up period. The incidence density of diabetes was 32.8/1000 person-year. After adjustment for age, fasting plasma glucose, 2-h plasma glucose, and waist circumference (WC), the Cox proportional hazards model showed that the subjects with A1C ≥ 5.5% had a 1.5-fold increased risk of new-onset diabetes compared to those with A1C < 5.5% (P=0.035). And the risk of diabetes incidence significantly increased with elevated A1C level (the hazard ratio reached 3.3 for the A1C6.4%). A1C5.5-6.4% detected 76.1% of all individuals at risk of subsequent incident diabetes. Our study suggested that A1C was indeed useful for screening and identifying individuals at a higher risk of diabetes among Chinese adults. Epidemiology/ Genetics WEIPING JIA, XUHONG HOU, JUNLING TANG, Shanghai, China EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING was 1.42 (1.21-1.67). When stratified by smoking categories, a U-shaped association between alcohol intake and diabetes risk was observed only in (s-a) category (HRs of (a-b), (a-c) and (a-d) compared to (a-a) were 0.85 (0.64-1.12), 1.04 (0.85-1.27) and 1.14 (0.91-1.43), respectively). There was no synergistic effect between these two lifestyle behaviors. In conclusion, the risk of development of T2DM increases with smoking and alcohol intake whereas there were no interactions. It is possible that the favorable effect of moderate alcohol intake would be reversed by smoking. at baseline. Subjects (mean age, 66.5 years; 68% men; mean HbA1c, 9.1%) were followed up for 5 years on average. When the patients were split into two groups according to HbA1c status at baseline with a cutoff point of 8.4%, the higher HbA1c group has significantly worse outcome than the lower group (Log-rank P=0.031). In the Cox-proportional hazards model, the overall hazard ratios of 1% increase of HbA1c were 1.22 (95% CI 1.09-1.36, P=0.0006) after adjustments for age, gender, smoking, estimated glomerular filtration rate, urinary albumin excretion corrected by creatinine, plasma brain natriuretic peptide level and prevalence of hypertension, CHD or HF at baseline. It is, therefore, concluded that uncontrolled diabetes is a significant risk for HF hospitalization independently of the baseline cadiorenal functions or cardiovascular comobidities. 1473-P Ratio of Trunk to Leg Volume Is Better Associated With Mortality than BMI or Waist Circumference JOSEPH P. WILSON, ALKA KANAYA, BO FAN, JOHN A. SHEPHERD, San Francisco, CA 1471-P Body shape is a known risk factor for diabetes and mortality, but the methods estimating body shape, BMI and waist circumference, are crude. We determined whether a novel body shape measure, trunk to leg volume ratio, was independently associated with mortality. We used the National Health and Nutrition Examination Survey 19992004 to generate dual-energy X-ray absorptiomery-derived trunk to leg volume ratio. Mortality data were linked with the National Death Index through 12/31/2006. Of 9862 adults with trunk to leg volume measures, 551(5.6%) died. The figure shows the total mortality (%) in each quartile of trunk to leg volume ratio by BMI category, with significant trends (p<0.001) for each category. Even among those with normal BMI, those in the highest quartile of trunk to leg volume ratio had a higher likelihood of death (5.5%) than those in the lowest quartile (0.2%). In a logistic regression model adjusting for age, sex, ethnicity, physical activity, and poverty index ratio, the odds of mortality comparing the fourth to first quartile of trunk to leg volume ratio was 1.76 (95% confidence interval, 1.20-2.60), 0.75 (0.67-0.84, per SD kg/m2) for BMI and was not significant for waist circumference. A high ratio of trunk to leg volume showed a strong association to mortality while BMI had a paradoxically inverse association. This novel body shape measure may provide additional information to better stratify individuals at risk for mortality, even among those with normal BMI. Comparison of IFCC Calibrated HbA1c for the Glucose, Fructosamine and HbA1c Study from Laboratory and Point of Care Testing POSTERS Epidemiology/ Genetics SUSAN E. MANLEY, RACHEL A. ROUND, PETER G. NIGHTINGALE, STEPHEN D. LUZIO, IRENE M. STRATTON, ROBERT CRAMB, STEPHEN C. GOUGH, JONATHAN WEBBER, Birmingham, United Kingdom, Swansea, United Kingdom, Gloucester, United Kingdom, Oxford, United Kingdom WHO and IDF recommend using HbA1c ≥6.5% [IFCC units 48 mmol/mol] for diagnosis of diabetes with pre-diabetes defined as 6.0% to 6.4% [42 to 47]. We have compared HbA1c results from several IFCC calibrated methods for a research study relating HbA1c to glucose and fructosamine. HbA1c was measured in 130 patients with diabetes on three IE HPLC analysers - Tosoh G8, Menarini HA8160 and Bio-Rad Variant II NU; two point of care systems - DCA 2000®+ analyser and A1cNow+™ disposable cartridges; an affinity chromatography analyser - Primus Ultra2 and compared to an IFCC secondary reference method - Menarini HA8160 calibrated according to protocol for an IFCC SRM laboratory. The median (IQ range) for HbA1c was 7.5(6.8 to 8.4)% [58(51 to 68)] on IFCC SRM with minimum value 5.3% [34] and maximum 11.9% [107]. There were significant positive offsets between IFCC SRM and Tosoh G8 analyser, mean difference (1SD), +0.22(0.21)% [2.4(2.3)], r2=0.973, p<0.001, and BioRad Variant II NU analyser +0.33(0.17)% [+3.6(1.9)], r2=0.984, p<0.001 with a very small negative difference for Menarini HA8160 analyser -0.03(0.11)% [-0.3(1.2)], r2=0.992, p<0.001. The POCT methods were less precise with negative offsets for DCA 2000®+ of -0.12(0.27)% [-1.3(3.0)], r=20.955, p<0.001 and A1cNow+™ -0.69(0.68)% [-7.6(7.5)], r2=0.691, p<0.001 (n=115). Small differences between IFCC calibrated methods across a wide range of HbA1c values were confirmed in internal quality control and national external quality assurance schemes. These offsets should be considered when evaluating data for individuals/cohorts of patients from different analysers especially when HbA1c is in the diagnostic range. Supported by: Novo Nordisk, Inc. 1472-P Combined Risk of Alcohol Intake and Smoking for Development of Type 2 Diabetes in the General Population in Japan: The Ibaraki Prefectural Health Study AYUMI SUGAWARA, TOSHIMI SAIRENCHI, KAZUYA FUJIHARA, FUJIKO IRIE, HIROSHI WATANABE, HIROAKI SUZUKI, HITOSHI SHIMANO, OSAMU HANYU, HIROHITO SONE, HITOSHI OTA, IBARAKI HEALTH PLAZA, Tsukuba, Japan, Shimotsugagun-Mibu, Japan, Mito, Japan, Niigata, Japan It is established that smoking increases the risk of development of type 2 diabetes mellitus (T2DM). Conversely, a U-shaped association was reported between alcohol intake and risk of diabetes, suggesting that moderate drinking could lower diabetes risk. However, the combined risk of these two lifestyle behaviors has not been elucidated despite the close association between rates of smoking and drinking. Data were obtained from the database of the Ibaraki Prefectural Health Study, a communitybased cohort study. 63865 men aged 40 to 79 y who completed an annual health checkup in 1993 were included. We excluded individuals with T2DM (≥7.0 mmol/L fasting or ≥11.1 mmol/L nonfasting or treatment) at baseline (n=3116), incomplete health checkup data (n=17155), and ex-smokers or exdrinkers (n=20671). Subsequently, 22923 men were eligible for analysis. The observation period began in 1993 to the date of development of T2DM or of the last health checkup in 2007. Smoking habits were classified into 3 categories: never smoker (s-a), smoking <20 cigarettes a day (s-b), and smoking ≥20 cigarettes/d (s-c). Alcohol intake was divided into 4 categories: never (a-a), drinking <15 g/d (a-b), 15- 30 g/d (a-c) and >30 g/d (a-d). Cox proportional hazard models showed that compared to the combination of (s-a) and (a-a), hazard ratio (95%CI) of the combination of (s-c) and (a-d) Supported by: National Science Foundation 1474-P Clinical Characteristics of People With Diabetes Mellitus in Guatemala (Central America): Do Guidelines Match Local Reality? FABIOLA PRADO DE NITSCH, MARIO A. NITSCH, Guatemala City, Guatemala We determined clinical characteristics and compared adequacy of international guidelines for diagnosis and treatment of Guatemalan diabetics. After informed consent, we obtained clinical history, weight, height, fingerstick blood glucose and HbA1c. Total sample was 931 diabetcs, 70% female. Average age 58 yr. Age at onset: 5 to 95 yr. 33 % of sample was younger than 45 years at onset of diabetes. 53% reported no symptoms at onset, 43% reported at least 1 classic symptom. Average BMI: 28,44 (± 5,18) kg/m² in women, and 27,33 (± 4,36) kg/ m² in men. 58% had BMI < 30 kg/m², and 35% and 24% of men and women, respectively, had BMI 18,5 - 24,99 kg/m². Diabetics with BMI < 25.0 kg/m² had higher A1c values than obese diabetics. Prevalence of morbid obesity: & For author disclosure information, see page 829. A384 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING 2%. No cases of super obesity documented. Average HbA1c 9.24%. 48% had A1c >= 9,0%, and 10% had A1c>= 14.0%. This sample differs in age and symptoms at onset, BMI and HbA1c values from international reports. No previous Guatemalan reports are available in the diabetic population. Presence of symptoms is not a good indicator for screening in the Guatemalan population. Overall, we documented poor glycemic control. Females, men with normal BMI, subjects younger than 65 years of age or younger than 45 years at diagnosis, and subjects with diabetes duration >= 5 years had higher A1c values than their counterparts, and thus a higher risk of microvascular complications. We must start generating nationwide information to set up diagnosis and treatment guidelines that ensure improvement of the poor glycemic control found, since international guidelines do not match local clinical reality. Differential diagnosis must include screening for LADA and malnutrition related diabetes in the normal weight diabetic population. We are working on developing new educational and prescribing strategies to improve glycemic control and reduce risk of complications in this Latino diabetic population. 1476-P Type 2 Diabetes Mellitus and Hepatocellular Carcinoma-Tumour Characteristics and Outcome 1475-P Zinc Transporter 8 Antibodies Can Replace IA-2 Antibodies as a Serological Marker for Type 1 Diabetes in India SHIVAPRASAD CHANNABASAPPA, PRASANNA KUMAR, MALA DHARMALINGAM, RAJNEESH MITTAL, Bangalore, India A high frequency of patients(45%) with presumed diagnosis of T1D in India lack GAD (GADA) and IA-2 autoantibodies (IA2A). As no data on ZnT8A in Indian population are available, the aim of our study was to estimate the prevalence of ZnT8A in T1D patients of Indian origin. 88 T1D patients <18yrs of age and duration of T1D < 48 months were recruited. Sex-matched healthy controls aged 2-18 years (n = 88) were also recruited. ZnT8A, GADA and IA-2A were esimated using commercial ELISA (DLD diagnotika,Germany). 68(77.3%) of patients were positive for atleast one antibody. ZnT8A were positive in 31.8% of patients. The prevalences of GADA and IA2A were 64.7% and 19.3% respectively. In newly diagnosed patients the prevalence of Znt8A was 45%. ZnT8A were positive in 26% of patients negative for both GADA and IA2A. Combined use of ZnT8A and GADA could detect 97% of antibody positive patients. Exclusion of IA2A didnot significantly reduce the proportion of patients with positivity for antibodies, implying that the utility of IA2A was limited and redundant. This study shows that ZnT8 antibody is a specific marker of juvenile-onset type 1 diabetes in India. The inclusion of ZnT8A in the antibody panel for screening of T1D in Indians can significantly increase the proportion of patients with antibody positivity to nearly 80%. ZnT8A can replace IA2A for screening autoimmunity in Indian T1D patients without loss of sensitivity or specificity. 1477-P Preoperative A1C and Clinical Outcomes in Surgical Patients With Diabetes RAJESH GARG, PATRICIA UNDERWOOD, REZA ASKARI, BINDU CHAMARTHI, ALI TAVAKKOLIZADEH, Boston, MA Acute hyperglycemia is associated with poor clinical outcomes in surgical patients. However, the impact of chronic hyperglycemia on surgical outcomes is not clear. We conducted a retrospective data analysis to investigate the effect of pre-operative A1C on clinical outcomes after surgery. Data were obtained from our Hospital’s National Surgical Quality Improvement Program (NSQIP) database and electronic medical records for 5 years, 2005 to 2010. Out of 1515 patients with diabetes, 364 had an A1C value (>6.5%) available within three months before surgery. These were divided into three groups: A1C 6.5-8%, 8-10% and >10%. Group wise patient characteristics and main outcomes are shown in table 1. Univariate regression analysis demonstrated that higher A1C was associated with increased length of hospital stay (LOS) (beta=0.51, p=0.009). This relationship remained significant after adjustments for age, gender, BMI, race, type of surgery and smoking status (p=0.02). Further, individuals with A1C ≥8% had significantly longer LOS compared to those without diabetes (7.6±6.9 vs 4.7±4.8 days; p<0.05). LOS did not differ between A1C <8% and non-diabetic individuals (5.4±5.7 vs 4.7±4.8 days; p=NS). There was no significant difference in other outcomes. We conclude that A1C ≥8% is associated with increased LOS after surgery. These data have implications for poorly controlled diabetic patients undergoing elective surgery. Table 1. Patient characteristics and main outcomes in A1C categories. N Age (years) Gender (Female %) Race (African American %) BMI (kg/m2) Surgery Type (Vascular %) Length of Hospital Stay (days) Deep surgical wound infections (%) Mortality within 30 days (%) Supported by: Endocrine Society of India ADA-Funded Research & Diabetes HbA1c 6.5-8% 217 60.5±13.6 115 (53%) 29 (13%) 36.0±10.6 50 (23%) 5.4±5.7 0.46% 2.76% Diabetes HbA1c 8-10% 98 58.2±13.4 48(49%) 17 (17%) 35.3±10.3 33 (34%) 7.9±6.9 2.04% 3.06% Diabetes p value for HbA1c>10% trend 49 54.0±12.2 25(51%) 10 (20%) 36.9±10.2 14 (29%) 7.0±6.8 2.04% 2.04% 0.009 NS NS NS NS 0.0009 NS NS For author disclosure information, see page 829. Guided Audio Tour poster A385 POSTERS Type 2 diabetes (DM2) is a risk factor for the development of hepatocellular carcinoma (HCC). However, the influence of DM2 on the tumour phenotype and survival in patients with HCC remains controversial. Therefore, we studied the tumour characteristics in patients with DM2 (DM2 group) vs non-diabetic patients (non-DM2 group) at the time of diagnosis of HCC, and correlated these findings with established prognostic factors (CLIP- Score), decisions of treatment and survival rates. We performed a single-centre retrospective analysis of n=252 patients with HCC treated in the last 12 years. In DM2patients, we found not only a better Child Pugh liver status than in non-DM2patients at the time of diagnosis (no cirrhosis 26 vs. 23%, liver cirrhosis [A] 59 vs 47%, [B] 14 vs 23%, [C] 1 vs 7%; p= 0.0114) but also a lower CLIP- Score, indicating a better prognosis, especially among patients with unifocal HCC (CLIP- Score [0-1], 94 vs 73%, Score [2-6] 6 vs 27%, p= 0.0035). In line with these findings, DM2- patients demonstrated higher survival rates, especially among patients with bad prognosis due to advanced disease (Mean survival in patients with CLIP- Score [2-6], DM2 vs non- DM2: 20 vs 11 months, p= 0,0155). No differences in AFP- levels and frequency of portal vein thrombosis were observed. Although both mean (103 vs 218 cm3, p=0.99) and total (178 vs 268 cm3, p=0,675) tumour volume were insignificantly smaller in the diabetic group, DM2 patients with multifocal HCC demonstrated significantly more lesions as non- DM2 patients (3,5 vs 2,9 n=104, p= 0,0278). No differences in treatment decisions (surgery, TACE, RFTA, drug therapy) were observed between the two groups. These results suggest that concomitant DM2 in patients with HCC is associated with multifocality of tumour lesions. However, DM2 patients have neither a worse prognosis at the time of diagnosis nor lower survival rates as non- DM2 patients with HCC. Epidemiology/ Genetics NIKOLAOS PERAKAKIS, APOSTOLIA LAMPRINOU, WERNER VACH, NADINE HENNECKE, ROBERT THIMME, HUBERT ERICH BLUM, KATHARINA LAUBNER, GÜNTER PÄTH, JOCHEN SEUFERT, Freiburg, Germany EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING 1478-P 1480-P Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients Serum Resistin Is Associated With HOMA and Matsuda-DeFronzo Insulin Sensitivity Index But Not Glucose Parameters During OGTT: The Toon Health Study POSTERS Epidemiology/ Genetics JACOB V. STIDSEN, REIMAR W. THOMSEN, JENS S. NIELSEN, JØRGEN RUNGBY, SINNA P. ULRICHSEN, SØREN FRIBORG, IVAN BRANDSLUND, JENS S. CHRISTIANSEN, HENRIK T. SØRENSEN, HENNING BECK-NIELSEN, Odense, Denmark, Aarhus, Denmark, Vejle, Denmark HIROSHI ONUMA, RYOICHI KAWAMURA, ISAO SAITO, YASUHARU TABARA, MAYO AIBIKI, YUKINOBU NOMI, YUKO KADOTA, AI OKAMOTO, TATSUYA NISHIMIYA, YASUNORI TAKATA, WATARU NISHIDA, TETSURO MIKI, TAKESHI TANIGAWA, HARUHIKO OSAWA, Toon, Japan, Kyoto, Japan Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. We investigated the prevalence of different pathophysiological phenotypes among newly diagnosed T2D patients in Denmark. Based on baseline data from a Danish national cohort study we investigated 1048 incident diagnosed T2D patients. The diagnosis T2D was made by general practitioners based on clinical judgement. Phenotypes were classified in the following groups: latent autoimmune diabetes (LADA) (GAD antibody titer >= 20 IE/ml and not T1D), secondary diabetes (recent history of pancreatitis, pancreatectomy or pancreas amylase > 65U/l, and GAD negativity), insulinopenic/non obese diabetes (f-P-C-peptide < 300 pmol/l and not LADA or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 600 pmol/l or waist circumference >= 94 cm for men and >=80 cm for women), steroid-induced diabetes (oral glucocorticoid-treated subjects) and a group not fitting into these phenotypes. Median age of our new T2D patients was 61 years (range 21-95 years), 57% were men. We found that 3.0% newly diagnosed T2D patients suffered from LADA, 3.9% from secondary diabetes, 4.1% had insulinopenic diabetes, 0.6% suffered from steroid induced diabetes whereas 84.8% presented the classic obesity-associated insulinresistant phenotype. Only 3.6% could not be classified within any of these 5 phenotypes. We conclude that newly diagnosed T2D patients represents several well-characterized pathophysiological phenotypes with various mechanisms of hyperglycemia. This should be taken into consideration when choosing the appropriate treatment for the individual patient diagnosed with T2D. We suggest to measure f-P-C-peptide, GAD antibodies and pancreas amylase in patients with newly diagnosed T2D. Resistin, secreted from adipocytes, antagonizes the action of insulin in mice. In humans, resistin is predominantly expressed in macrophages, and its expression is induced by inflammation. However, the association of serum resistin and insulin resistance is controversial in humans. The relation between serum resistin and either insulin resistance or secretion based on oral glucose tolerance test (OGTT) in general populations remains to be elucidated. The Toon Health Study is a cohort study for surveying risk factors for cardiovascular diseases and diabetes in community based subjects. In this study, 2,033 residents aged 30-79 years were enrolled from 2009 to 2012. In 1,936 subjects, a 75g OGTT was performed and plasma glucose (PG) and insulin were measured at 0, 1, and 2 hours. Serum resistin was measured by ELISA. Resistin, homeostasis model assessment insulin resistance (HOMAIR), HOMAβ, and Matsuda-DeFronzo insulin sensitivity index (ISI-M) were natural log-transformed for statistical analyses. Serum resistin was positively correlated with HOMA-IR and HOMAβ, and inversely correlated with ISI-M (correlation coefficient [R] = 0.14, 0.15, and -0.12, respectively, all P<0.0001). A multiple regression analysis showed that these associations did not change after adjusted for age, sex, and BMI (standardized β=0.12, 0.12, and -0.09; P <0.0001, <0.0001, and 0.004, respectively). Serum resistin was not associated with fasting PG, 1-h PG, 2-h PG, and glucose area under the curve (AUC) during OGTT. In summary, serum resistin was associated with HOMA-IR, HOMAβ, and ISI-M but not glucose parameters during OGTT. Serum resistin appeared to be asscociated with insulin resistance, but insulin secretion capacity could have stronger effects on glucose tolerance. Supported by: Danish Council for Strategic Research 1481-P 1479-P Functional Status of Patients With Type 2 Diabetes Mellitus: Is It the Diagnosis or Underlying Risk Factors Promoting Ill Health? Effects of Recommendation Notices for Clinic Visits by Nationwide Health Screening System in Japan HAROLD E. BAYS, KATHLEEN M. FOX, SUSAN GRANDY, SHIELD STUDY GROUP, Louisville, KY, Monkton, MD, Wilmington, DE OSAMU HANYU, YORIKO HEIANZA, KAZUO FURUKAWA, RYO KAWADA, MASAHIKO YAMAMOTO, TAEKO OSAWA, HIROMI SUZUKI, SHIN-ICHI MINAGAWA, TAKAHO YAMADA, AYAKO YAMADA, AKIKO SUZUKI, HIROHITO SONE, Niigata, Japan Adults with type 2 diabetes mellitus (T2DM) often have diminished functioning. This may be due to the implications associated with the diagnosis of T2DM or to underlying characteristics that predispose to T2DM and ill health. Adult respondents to the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) were classified into 3 groups: (1) T2DM diagnosis at baseline in 2004, (2) newly diagnosed with T2DM from 2005-2009 (ie, “at risk” for T2DM at baseline), and (3) no T2DM diagnosis at baseline or from 2004-2009. Self-reported functioning scales included SF-12 (physical and mental health), PHQ-9 (depression), IPAQ (physical activity) and WPAI (work impairment). Regression models adjusted for age, obesity, current smoking, cholesterol problems, heart disease and hypertension. In total, 1837 (26%) respondents reported T2DM at baseline, 473 (7%) reported newly diagnosed T2DM during the study, and 4629 (67%) reported no T2DM at study end. SF-12 physical health scores were similar for T2DM (40.7) and newly diagnosed T2DM (41.6) (p >0.05) but worse compared with no T2DM (46.5) (p<0.01). Depression scores and work impairment were similar for T2DM and newly diagnosed T2DM (4.86 vs. 4.99 for depression; 11.9 vs. 12.8 for work impairment, p>0.05) but worse than no T2DM (4.03 for depression; 9.5 for work impairment, p<0.01). T2DM (12%) and newly diagnosed T2DM (12%) respondents were significantly less physically active than those with no T2DM (16%) (p<0.01). Age, obesity, cholesterol problems, smoking and T2DM status consistently predicted scale scores after adjusting for other predictors in the model. This survey suggests that self-reported functioning scale scores may be similar between T2DM respondents and those who subsequently developed T2DM. Both groups had significantly worse scores compared with those with no T2DM - an effect substantially correlated with age, obesity, cholesterol problems and smoking. Early detection and continued interventions for cardiovascular risk factors including diabetes/prediabetes, hypertension, and dyslipidemia are crucial to prevent atherosclerotic disease. Japan launched a nationwide health screening system in 2008 to detect these asymptomatic disorders at an early stage to provide continuous interventions. Subjects classified as at high risk receive notices recommending clinic visits and are expected to make regular clinic visits for interventions and check-ups thereafter. However, the effect of these notices on actual clinic visit rates is unknown. We determined the clinic visit rate after such notices from information on health records and health insurance claims. Health records and insurance claims between April 2010 and March 2011 of 117,952 adults aged 40-74 y (59,567 males; 58,385 females) were obtained from the Japan Medical Data Center Co., Ltd. This is a representative sample since these individuals resided throughout Japan. Criteria for a clinic visit were systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg, low-density lipoprotein cholesterol (LDL-C) >140 mg/dL or Hb-A1c >6.5%. Subjects already diagnosed with hypertension, dyslipidemia or diabetes were excluded. Proportions of screenees requested to make a visit clinic were 16% for high blood pressure, 29% for high LDL-C and 2% for high HbA1c. However, only 12% of those contacted for high blood pressure, 12% for high LDL-C level and 32% for high HbA1c actually made a clinic visit. Rates were lowest among younger subjects (40-49 y). Rates of continuation of clinic visits 12 mo after the notice declined to 7% for blood pressure, 5% for LDL-C and 16% for Hb-A1c, with rates also lowest in subjects aged 40-49 y. These results indicated unsatisfactory and transient results of notices for clinic visits based on nationwide health screening especially in younger people. Further novel strategies should be developed to improve consultation/continuation rates for intervention. Supported by: AstraZeneca & For author disclosure information, see page 829. A386 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING 1482-P 1484-P Serum Ficolin-3 as a New Biomarker Predicting the Development of Type 2 Diabetes WITHDRAWN 1485-P 1483-P African Immigrant Men have a Lower Waist Circumference of Risk than African American Men Hyperglycemia and Hypoglycemia on Admission are Associated With Adverse Outcomes Among Hospitalized Patients With or Without Diabetes MICHELLE Y. O’CONNOR, MADIA RICKS, NATALIE L. RAMSEY, FRANCINE THOMAS, PETER T. KATZMARZYK, JIANHUA YAO, ANNE E. SUMNER, Bethesda, MD, Baton Rouge, LA ROGERIO S. RIBEIRO, DOMINGOS A.C. MALERBI, JOÃO R. SÁ, RICARDO B. PERES, SIMÃO A. LOTTENBERG, MARIA L.M. COSTA, MAGDA T. YAMAMOTO, CLAUDIA R. LASELVA, JOSE A.M. CARVALHO, São Paulo, Brazil Whether the waist circumference (WC) of risk differs among populations of African descent is unknown. Defining the “WC of risk” as the WC which best predicts insulin resistance, WC of risk was compared in age-matched African-American (AA) and African immigrant men. Data on 180 nondiabetic men (43% AA, age 36±9y, mean±SD) were analyzed. Africans lived in US for 10±9y. In the first 5y after immigration, weight gain per year was ~3 kg. Insulin resistance was defined by the lowest quartile of the insulin sensitivity index (SI<2.34). Receiver operating characteristic (ROC) curves and the Youden Index were used to identify the optimal WC. BMI was lower in Africans than AA (27.0±3.7 vs. 29.6±6.2 kg/m2, P<0.01). Adjusting for BMI, WC did not differ by ethnicity (93±56 vs. 93±48 cm, P=0.4), but Africans had higher VAT (P<0.01) and lower SAT (P<0.05). The WC which best predicted insulin resistance in Africans was 93 cm (AUC-ROC: 0.71) and in AA was 100 cm (AUC-ROC: 0.78). At every level of WC, VAT was higher in Africans than AA (Figure). Hence, the WC of risk is lower in African than AA men. In Africans, rapid weight gain after immigration may account for higher VAT and greater insulin resistance at a lower WC. Overall, for populations in transition, the WC of risk may take time to determine. Objective: To study the association between glucose abnormalities on admission and adverse outcomes among hospitalized patients with or without diabetes. Methods: We retrospectively examined the frequency of hyper (> 10 mmol/l or 180 mg/dl) and hypoglycemia (< 3.9 mmol/l or 70 mg/dl) and its association with adverse outcomes among 23098 non-pregnant hospitalized adults who underwent capillary glucose (Abbott Xceed Pro, CV 6%) screening on admission, representing 94% of total admissions in a tertiary private hospital during 2011. Patients were classified according to diabetes status. Adverse outcomes included length of stay (LOS), infection, admission to intensive care unit (ICU) and mortality. For patients with multiple hospitalizations, only the first admission was considered. Statistical significance was defined as P<0.05. Results: Among 2913 patients with diabetes, hyper and hypoglycemia were detected in 982 (33,7%) and 99 (3,4%) admissions, respectively. Hyperglycemia was associated with increased LOS (7,05±14 vs. 4,06±8 days), infections (21,2 vs. 14,4%), ICU admissions (24,9 vs. 14%), and mortality (2,6 vs. 0,5%), compared to normoglycemia. Hypoglycemia was associated with increased LOS and mortality (3%). Among 20185 patients without diabetes, hyper and hypoglycemia were detected in 871 (4,3%) and 628 (3,0%) admissions, respectively. Hyperglycemia was associated with increased LOS (14,7 vs. 3,6 days), infections (28 vs. 13%), ICU admissions (44 vs. 8%) and mortality (10 vs. 0,9%), compared to normoglycemia. Hypoglycemia was associated with increased mortality (2%). Conclusion: Capillary glucose screening on admission may detect hyperglycemia and hypoglycemia and indicate poor prognosis in hospitalized patients with and without diabetes. ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A387 POSTERS It is reported that toll-like receptor, one of the membrane-bound pattern recognition receptor (PRR) plays an important role in insulin resistance(IR). Ficolin-3, a soluble pattern recognition receptor (PRR) within the lectin component of the complement pathway, share the same structure and function with MBL, was found to be significantly different between normal glucose tolerance (NGT) and type 2 diabetic patients in our study. To investigate whether serum ficolin-3 associates with type 2 diabetes (T2DM) and predicts the incidence of T2DM independent of established risk factors in Shanghai Diabetes Study. 1742 subjects with NGT, 209 subjects with impaired glucose regulation (IGR),and 145 subjects with type 2 diabetes, whom were followed prospectively to assess the development of type 2 diabetes for average 3 years. 130 subjects developed type 2 diabetes. Baseline serum ficolin-3 levels were measured with ELISA. The role of ficolin-3 in predicting the development of type 2 diabetes over 3 years was investigated using logistic regression analysis. At baseline, serum ficolin-3 was significantly lower in T2DM and IGR subjects, and independently correlated with the index of homeostasis model (HOMA-IR). A decreased serum ficolin-3 was independently associated with T2DM. In the prospective study, 130 incident diabetic subjects were identified in the full cohort during 3 years follow up. Decreased serum ficolin-3 was associated with increased type 2 diabetes risk after adjustment for age. The association remained significant after adjustment for age, sex, BMI, waist circumference. Furthermore, decreased serum ficolin-3 was associated with type 2 diabetes risk particularly in individuals with female, hyperglycemia, non-abdominal obesity, hypertention, and dislipidemia. Decreased serum ficolin-3 was strongly and independently associated with T2DM and lower ficolin-3 levels predicted the development of type 2 diabetes in this Chinese cohort. Epidemiology/ Genetics HAIBING CHEN, WEIPING JIA, Shanghai, China POSTERS Epidemiology/ Genetics EPIDEMIOLOGY—CLINICAL—DIAGNOSIS AND SCREENING 1486-P 1488-P Elevated Serum Ferritin Level Is Associated With the Development of Diabetes in Healthy Korean Men: A 4-Year Retrospective Longitudinal Study Random Exmination of Blood Glucose in Adults by Trained Volunteers in a Hospital Setting CHANG HEE JUNG, JAECHAN LEEM, JOONG-YEOL PARK, HONG-KYU KIM, WOO JE LEE, Seoul, Republic of Korea Screening for dysglycemia can be conducted by trained volunteers in a public location. The study was designed to examine the incidence of dysglycemia and diabetes among screened, non hospitalized subjects in a pubic setting. A diabetes screening station staffed by trained volunteers was situated in the main entrance lobby of E. Wolfson Medical Center, Holon. Volunteers measured height, weight, blood glucose (by glucometer) and blood pressure (by sphygmomanometer). Screened subjects were asked whether they had diabetes. Dysglycemia was defined as blood glucose 140< 200 mg/dl and diabetes as ≥200mg/dl. Screening was performed free of charge. A total of 9994 individuals (54.1 females, 55±15.1 years) underwent screening. Of these, 1589 (15.9%) reported known diabetes. Among the 7868 subjects without known diabetes, dysglycemia was detected in 1065 (13.5%) and diabetes was found in 115 (1.5%). Compared to subjects with blood glucose < 140 mg/dl, those with dysglycemia were significantly older (58±14 vs. 51.5±15.2 years, p< 0.001) and had elevated BMI (27.4±4.6 vs. 26.4±4.5 kg/m2, p< 0.001), systolic blood pressure (137.4±22.9 mmHg vs. 131.9±21.6 mmHg, p< 0.001) and diastolic blood pressure (80.3±16.2 vs. 78.8±14.3, p=0.004). Compared to subjects with newly identified dysglycemia, those with newly identified diabetes had significantly higher diastolic blood pressure (86.4±23.3 mmHg, p< 0.001) but did not differ by age, BMI or systolic blood pressure. Implementation of a screening program in public places can identify people at high risk for dysglycemia and diabetes, who are referred for diagnosis and treatment. MONA BOAZ, YOSEFA BAR DAYAN, JULIO WAINSTEIN, Holon, Israel Accumulating evidence, mostly from studies conducted in Western populations, has demonstrated strong association between ferritin concentrations and the development of type 2 diabetes (T2D). In Asian populations, however, there was no research to examine whether serum ferritin levels have been actually associated with the prospective development of T2D. Considering both the different levels of serum ferritin between different ethnicities and the diverse effect of body composition according to the ethnicities on the association between serum ferritin and the insulin resistance, it still remains unclear whether elevated ferritin levels contribute to the development of T2D in Asian populations. In this 4-year retrospective longitudinal study, we aimed to investigate the role of elevated levels of serum ferritin in the development of T2D in a healthy Korean male population. After excluding ineligible subjects, we examined the clinical and laboratory data of 2,029 male subjects (mean age, 51.2 yr, range, 23-82 yr) without T2D who underwent general routine health evaluations at the Asan Medical Center (Seoul, Republic of Korea) in 2007 and had returned for follow-up examination in 2011. During a 4-year period, 186 incident diabetes cases (9.2 %) were identified. We could observe that incident T2D increased across the baseline ferritin quartile categories (P for trend = 0.003). The odds ratios (ORs) for the development of T2D were significantly higher in highest compared with the lowest ferritin quartile categories, even after adjustment for confounding variables including HOMA-IR (OR=1.25, 95% confidence interval 1.34-2.22, P for trend=0.046). These results suggest that elevated levels of serum ferritin is associated with the development of T2D in an Asian population as well. To our best knowledge, this is the first prospective study on the positive association between serum ferritin levels and incident T2D in an Asian population. 1489-P Evaluation of Different Methods in HbA1c Interference NILGUN SEMA GENC, MUGE KANMAZ-OZER, BEYHAN OMER, FIGEN GURDOL, NEVIN DINCAG, Istanbul, Turkey Background: Hemoglobin A1c(HbA1c) assay is the most powerful marker to determine the glycemic control in diabetic patients.In this study, we aimed to evaluate the analytical performances of the Roche Tina-quant HbA1c assay based on immunoturbidimetry(TINIA), TosohG8 cation-exchange high-performance liquid chromatography and Premier Hb9210 boronate affinity chromatography methods.Sebia capillary zone electrophoresis was performed as the reference method.The degree of interference was examined by high urea and triglyceride levels on HbA1c analysis. Methods: This study comprised 204 whole blood samples obtained from the diabetic and nondiabetic patients.HbA1c levels were quantified in quadriplicate using four different methods. Results: The results of precision studies (within-run and betweendays) were under 2.5% CV as specified by IFCC working group for the HbA1c standardization.The Deming Regression analysis between capillary electrophoresis and other methods were evaluated, good correlation was seen between capillary electrophoresis and TINIA and boronate affinity chromatography as well. HPLC method also showed a good correlation but was not in good agreement, because the confidence interval for slope did not contain zero and intercept value. The HbA1c results with either normal or high urea and tryglycerid levels were examined to detect the interference of these substances.No significant differences were seen between the reference method and other methods studied. Conclusion: HbA1c results of the diabetic patients are not affected by the accompanied metabolic disorders such as uremia and hypertriglyceridemia. Therefore, these conditions may be ignored during the clinical evaluation of the patient. 1487-P A1c ≥ 6.5% Misses the Majority of Diabetic Patients Defined by Plasma Glucose HORNG-YIH OU, JEAN HUANG, RUDRUIDEE KARNCHANASORN, WEI FENG, RAYNALD SAMOA, KEN C. CHIU, LEE-MING CHUANG, Tainan, Taiwan, Sylmar, CA, Kansas City, KS, Duarte, CA, Taipei, Taiwan Diagnosis of diabetes mellitus (DM) was originally made on blood glucose from a fasting sample or oral glucose tolerance tests, based on the risk of retinopathy, namely 126 mg/dL for fasting plasma glucose (FPG) and 200 mg/dL for 2-hour post-challenged plasma glucose (2hPG). In 2012, the ADA officially adapted a hemoglobin A1c (A1c) ≥ 6.5% into its criteria for the diagnosis of DM, which was also based on the risk of retinopathy. In this study, we examined the performance of A1c in the diagnosis of diabetes as compared to the diagnosis by FPG and 2hPG. This study consisted of the participants of the NHANES 2005-2010. Only the subjects aged 18 years old or older that had an A1c, FPG, and 2hPG were enrolled into this study (n=5,796). After all established cases of diabetes were excluded, 5,745 subjects were remained in this study. Consistent with current ADA guideline, DM was defined as either FPG ≥ 126 mg/dL or 2hPG ≥ 200 mg/dL. In this sample, 479 subjects (8.34%) were found to be diabetes. Among them, only 119 subjects (24.84%) had an A1c ≥ 6.5%, while 360 subjects (75.16%) had an A1c < 6.5%. As compared to the DM subjects with A1c ≥ 6.5%, the diabetic subjects with A1c < 6.5% were leaner (29.92±6.43 vs. 32.98±6.82 kg/m2, mean±STD, P=0.00001). However, no difference was found in gender distribution, age, systolic and diastolic pressure, and family history of DM. For diabetic subjects with BMI of 20.00-24.99 kg/m2, 84.81% of them had A1c < 6.5%. We found that A1c was correlated with FPG very well (r=0.6987, P<0.000001) and also with 2hPG very well (r=0.5906, P<0.000001). Jointly FPG and 2hPG accounted for 51.11% of variation in A1c (P<0.000001). Based on this relationship with FPG of 126 mg/dL and 2hPG of 200 mg/dL, A1c was 6.1037%. In summary, A1c ≥ 6.5% will detect less than 25% of subjects with DM defined by either FPG or 2hPG with very low sensitivity in lean subjects. This study suggests that to be consistent with FPG and 2hPG cutoffs, a new diagnostic criterion for DM, such as an A1c > 6.1% as defined in this study, is required. 1490-P Meal Tolerance Test Is More Valuable than Glucagon Stimulation Test in Type 2 Diabetes YOUHEI FUJIOKA, TSUYOSHI OHKURA, KEISUKE SUMI, HIDEKI SHIOCHI, NAOYA YAMAMOTO, KAZUHIKO MATSUZAWA, SHOICHIRO IZAWA, HIROSHI KINOSHITA, HIROKO OHKURA, MASAHIKO KATO, SHINICHI TANIGUCHI, KAZUHIRO YAMAMOTO, Yonago, Japan Glucagon stimulation test (GST) is a standard method of evaluating endogenous insulin secretion. However, GST has adverse effects and takes effort. In contrast, meal tolerance test (MTT) has no adverse effect and cheaper than GST. The aim of this study is to evaluate the properties of GST and MTT in type 2 diabetes patients. We enrolled sixty-nine patients of type2 diabetes (mean: age 61.3, M/F: 34/35, BMI: 24.2, HbA1c: 9.5) and performed GST and MTT. We performed MTT by using a normal diabetes food of 30kcal/ day per ideal body weight, which contains 60% of carbohydrates, protein 20%, & For author disclosure information, see page 829. A388 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—DIABETES COMPLICATIONS lipid 20%. In MTT, patients continued oral hypoglycemic agents and insulin treatment as usual, but we excluded patients taking glinide from subjects to exclude influence of the medicine. In MTT, we measured plasma glucose (PG) and serum C-peptide immunoreactivity (CPR), and plasma insulin level before and 120minutes after meal load. We calculated increment of CPR (ΔCPR) by subtracting fasting CPR (FCPR) from 6 minutes after glucagon injection and 120 minutes after meal load. The mean fasting PG (FPG) was 161 mg/dl, the mean FCPR was 2.2 ng/ml, the mean GSTΔCPR was 2.1 ng/ml, and the mean MTTΔCPR was 3.0 ng/ml. The mean MTTΔCPR was significantly higher than the mean GSTΔCPR (P<0.01). To consider influence of glucotoxicity to both test, we performed ROC analysis by FPG. The optimal cut point of was under 157 mg/dl to define MTT superior to GST (sensitivity 0.75, specificity 0.67, AUC 0.70). MTT could examine insulin secretion including incretin effect by the meal load, and it may be one of the reasons why MTTΔCPR is higher than GSTΔCPR. Therefore, MTT could evaluate the endogenous insulin secretion ability more than GST. However, MTT is affected by the glucotoxicity than GST. We had better consider to perform GST in the hyperglycemic state, especially FPG is 157mg/dl or more. We need to use GST and MTT properly by a level of FPG. In conclusion, MTT is more valuable as an insulin secretion test in type 2 diabetes patients than GST. 1492-P Abnormal Glycoregulation in Chinese Patients With Graves Disease 1491-P Relationship between Body Weight (BW) Gain from Early Adulthood and Incident Type 2 Diabetes (T2DM): A Meta-Analysis SATORU KODAMA, CHIKA HORIKAWA, KAZUYA FUJIHARA, RYOKO TAJIMA, YORIKO HEIANZA, YOKO YACHI, KAORUKO T. IIDA, HITOSHI SHIMANO, OSAMU HANYU, HIROHITO SONE, Mito, Japan, Tsukuba, Japan, Tokyo, Japan, Niigata, Japan Our aim of this meta-analysis is to ascertain the shape of the relationship between BW gain and risk of future T2DM. Electronic literature searches were conducted for prospective studies investigating T2DM risk in relation to BW change from early adulthood (18-24 y) to cohort entry using MEDLINE and EMBASE. Excluded were studies that included participants with diabetes or were <25 y of age. For 7 eligible studies, the natural logarithms of relative risk (ln RR) of diabetes in all risk groups with BW gain compared with a referent group that maintained BW were plotted against their corresponding mean dose of BW gain standardized into body mass index (BMI) units. Linear and spline regression analyses were applied for ascertaining the shape of the scattered plots. Linear regression analysis indicated that RR (95% confidence interval) for a 1 kg/m2 incremental increase in BMI was 1.18 (1.151.22). Spline curve revealed higher goodness of fit compared with linearity (R2=0.85 vs. 0.75, P for difference <0.001). However, no critical point of BW gain above which T2DM risk rapidly increased was detected (Figure). Results of this meta-analysis suggested that T2DM risk continuously increased with BW gain without a cut-off value below which the increase in T2DM risk was avoided. EPIDEMIOLOGY—DIABETES COMPLICATIONS Guided Audio Tour: Epidemiology of Diabetes Complications (Posters: 1493-P to 1499-P), see page 15. & 1493-P Epidemiology of Hypoglycemia and Its Impact on Health-Related Quality of Life in Type 2 Diabetes Mellitus (HYPO-Cyprus) CHRISTINA THERAPONTOS, PETROS MAVROGENIS, SIEW HWA ONG, STAVROS POULOUKAS, CHRISTOS PASTELLAS, MARINELLA KYRIAKIDOU-HIMONAS, PANAYIOTIS KOUTSIDES, GEORGE OLYMPIOS, MICHALIS PICOLOS, ANDREAS STYLIANOU, COSTAS TOUFEXIS, POLYKARPOS EVRIPIDOU, THEODOROS LOIZOU, Nicosia, Cyprus, Basel, Switzerland, Limassol, Cyprus, Larnaca, Cyprus HYPO-Cyprus was a cross-sectional epidemiological study designed to evaluate the incidence of hypoglycemia and its impact on health-related quality of life (HRQoL) as a function of patient perspectives, HRQoL scores, treatment satisfaction and current health status. 500 adult Cypriot type 2 diabetes mellitus (T2DM) patients were asked to report their hypoglycemia frequency and experience (using Hypoglycemia Perspectives Questionnaire), HRQoL (using Audit of Diabetes Dependent Quality of Life-19 questionnaire), treatment satisfaction (using Treatment Satisfaction questionnaire) and current health status (using EuroQol-5 Dimensions questionnaire). Demographical and clinical characteristics (including HbA1c value and current medication) were also recorded. Hypoglycemia was reported by 45.0% of patients, with a frequency of 0.71±1.37 events in the past 7 days and 2.39±14.39 severe events in the past year. 59.8% of hypoglycemic patients were uncontrolled (HbA1c≥7%). On average, patients who experienced hypoglycemia were less concerned about symptoms (p<0.05), used more compensatory behaviors (p<0.001) and scored higher on awareness of hypoglycemia (p<0.001) than patients who did not. The reported HRQoL score for hypoglycemic patients was lower than non-hypoglycemic patients (average weighted impact score: -2.50 versus -1.99, p<0.01), with significant differences in travel (p<0.05), holidays (p<0.05), physical activities (p<0.001), sex life (p<0.05), self-confidence (p<0.01), motivation (p<0.05) and financial situation (p<0.05). Satisfaction with treatment (p<0.05) and current health (p<0.001 for EQ-5D descriptive system; p<0.05 for EQ VAS) were also reduced in hypoglycemic patients. In conclusion, hypoglycemia: 1) was reported by approximately one ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A389 POSTERS We selected 85 patients with Graves’ disease in our hospital from August 2010 to June 2012, and divided them into 3 groups, primary treatment group (GD1group), treatment group (the course was 2±0.5month, symptom uncontroled,GD2group), titration period group (the course was 4±1.5 months, thyroid hormones were within normal, symptom controlled, GD3 group), and also 30 healthy persons as control (NC group). All patients were treated by ATD for 6 months and evaluated before and after the treatment. At baseline, BG level of GD groups at 30, 60, 120, 180min after OGTT were markedly higher than the NC group (P<0.01). BG and insulin level rose to a peak level at 30min and 60 min respectively, and then declined with the time. BG and insulin level post treatment were decreased significantly (P<0.01), but still higher compared with NC group (P<0.01). At baseline,BG and insulin level of GD1 group and GD2 group were significantly higer than GD3 group (P<0.01). BG and insulin level of GD groups post treatmen had no difference (P>0.05). At baseline, the ΔI30/ΔG30 of GD groups were significantly lower than NC group (P<0.01), and there was not markedly increase after treatment(P>0.05). SG, SI of GD groups at baseline were significantly higher than NC group (P<0.01), and decreased significantly (P<0.01) after treatment, but still higher than NC group(P<0.01). At baseline, the ΔI30/ΔG30 of GD groups had no difference (P>0.05), the SG, SI of GD1 group and GD2 group were significantly higher compared with GD3 group (P<0.01), and these index had no differenc post tretment (P>0.05).These results suggest most of patients with Graves’ disease might manifest with fasting hypoglycemia, impaired glucose tolerance (IGT), insulin resistance, and hyperinsulinemia. Insulin resistance and β-cell dysfunction coexist in patients with Graves’ disease. Treatment by ATD can improve insulin resistance, but islet βcell function will remained low for a very long period. Epidemiology/ Genetics QINGXIAN HUANG, QIAN LIU, WEIKAI HOU, KUN WANG, SHAN YU, LI CHEN, Jinan, China EPIDEMIOLOGY—DIABETES COMPLICATIONS half of the studied T2DM sample; 2) was associated with higher levels of uncontrolled diabetes and 3) had a negative impact on HRQoL of Cypriot T2DM patients. & Supported by: Novartis Pharmaceuticals Corporation SHUBARNA AMIN, S. JOSEPH KIM, BAIJU R. SHAH, Toronto, ON, Canada & This study examined the risk of chronic kidney disease (CKD) in South Asian and Chinese people after diabetes diagnosis, compared to the general population. Using population-level healthcare databases in Ontario, Canada, all 769,554 people diagnosed with diabetes from January 1996 to December 2007 were followed until March 2012 for CKD using physician claims and hospitalization data with validated algorithms. South Asian and Chinese patients were identified by surname; all other patients were in the general population. Groups were compared using Cox regression models, adjusting for demographic differences, hypertension and cardiovascular disease. A comparison group without diabetes was also examined, and the effect modification of diabetes on CKD risk was tested using an interaction term. Compared to the general population, South Asian [HR 0.84 (95% CI 0.800.87)] and Chinese [0.91 (0.87-0.95)] people had a lower risk for CKD after diabetes diagnosis. However, these ethnic differences in CKD risk were no different from ethnic differences in CKD risk in the comparison population without diabetes (p for interaction term=0.06 for South Asians, 0.6 for Chinese). South Asian and Chinese patients had a lower risk of CKD after diabetes diagnosis than those in the general population. These ethnic differences mirrored the ethnic differences in CKD risk of people without diabetes, suggesting no diabetes-specific effect of ethnicity on CKD risk. 1494-P Falling or Static National Rates of Diabetes-Related Outcomes from 2005 to 2011 Despite Increasing Prevalence POSTERS PAUL L. DRURY, PAULINE W. GILES, EMMANUEL JO, Palmerston North, New Zealand, Wellington, New Zealand Epidemiology/ Genetics 1496-P Ethnic Differences in the Risk of Chronic Kidney Disease After Diabetes Diagnosis Despite rapid and substantial increases in the national diabetes (DM) population at risk in New Zealand (NZ), anecdotally we have not seen the anticipated rise in adverse outcomes for renal and vascular morbidities. We have therefore assessed the annual number of lower-limb amputations, renal replacement therapy access procedures, cardiovascular (CV) events and strokes occurring throughout NZ over the 6 year period 2006-2011 using standard data collection and coding methods. All such events, identified by ICD-9 or ICD-10 coding, can be linked by a unique national patient identifier available for >98% of people. We used a detailed algorithm, the NZ Virtual Diabetes Register (VDR), to define the population with DM; this identifies individuals as having DM based on their specific healthcare facility and therapy usage with ≥ 90-95% sensitivity and specificity. Diabetes prevalence using the VDR rose from 138,200 (end-2005) to 208,076 (end2011), an increase of 50.6% over 6 years - 7.0% compound per annum (p.a.), while total national population rose only 7.3% (4.12 to 4.42 million) over this period. Lower limb amputations in people with DM remained roughly static between 648 and 782 events annually while, as a rate per 1000 people with DM, this fell sequentially from 0.47% to 0.39% p.a. (-17%; P<0.05). Renal access procedures also remained static between 422 and 548 events annually (0.24-0.33% p.a.; p=NS) with no clear trend. Both the absolute number and rate of CV events fell progressively from over 13,000 to below 11,000 (9.48 to 5.74% p.a., -39% ; r= -0.97; p<0.005). Stroke events rose in absolute numbers from 2600 to 3300 but the rate fell from 1.90 to 1.73% p.a.(-9%; r= -0.90, p<0.02). We conclude that, despite a 50% increase in diabetes prevalence, national major end-point rates are currently either static or falling, particularly so for CV events. This probably largely reflects more systematic care, wider use of CV and renal preventative therapy together with improved footcare. & 1495-P The Effects of Smoking on Glycemic Control and Microvascular Complications in Type 1 Diabetes in the Diabetes Control and Complications Trial (DCCT) & BARBARA H. BRAFFETT, MADELINE M. RICE, HEATHER YOUNG, JOHN M. LACHIN, Washington, DC 1497-P Diabetes Status and Incidence of Cancer After Age 65, U.S. 1988– 2007 Several studies have demonstrated the significant effects of smoking on the risk of microvascular complications, however, few have also examined the mediating effects of HbA1c. Using publicly available data from the wellcharacterized cohort of 1,441 subjects with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT), we describe the acute and long-term risks of smoking on glycemic control and microvascular complications (nephropathy and retinopathy). Over a mean of 6.5 years of follow-up, the DCCT recorded self-reported smoking behaviors, glycemic exposure based on HbA1c values, and complication status. Generalized linear mixed models were used to assess whether time-dependent measurements of smoking predict HbA1c levels. Cox proportional hazard models were used to assess time-dependent smoking exposures as predictors of nephropathy and retinopathy. All models were adjusted for potential baseline confounders. During the DCCT, current smokers had consistently higher HbA1c values compared with former and never smokers (0.35% mean difference vs. never smokers; 0.29% mean difference vs. former smokers). Additionally, current smokers had a 42% higher risk of retinopathy and 34% higher risk of nephropathy compared with never smokers. The significant associations between smoking and complications were fully attenuated after adjusting for HbA1c. Former smokers did not differ significantly from never smokers with respect to HbA1c and the risk of complications. Smoking is associated with poor glycemic control and an increased risk of microvascular complications in individuals with type 1 diabetes. Our data suggest that the negative effects of smoking on glycemic control may be a mechanism by which smoking leads to complications of type 1 diabetes. The harmful effects of smoking on HbA1c and the risk of complications may not persist after quitting smoking, SHARON H. SAYDAH, KAI M. BULLARD, GIUSEPPINA IMPERATORE, EDWARD GREGG, LISA RICHARDSON, JEFFERY JOHNSON, Washington, DC, Atlanta, GA, Alberta, AB, Canada Although many studies reported the association between diabetes and cancer, few studies have examined the difference in cancer incidence between pre-diabetes and diabetes (DM) status and fewer have focused on the population aged 65 years and older. This study’s objective was to determine the risk of cancer incidence among the Medicare population by elevated glucose status. We used data from the National Health and Nutrition Examination Surveys (NHANES:1988-1994 and 1999-2004), linked CMS Medicare files through 2007. We included 4,552 adults aged ≥65 years at the time of NHANES interview with no prior history of cancer and no enrolment in a Health Maintenance Organization prior to 2007. Diabetes status was defined as follows: treated DM (DM + antidiabetic medication); untreated DM (DM + no medication, or no DM + A1c>=6.5%); prediabetes (no DM + A1c 5.7-6.4%); normoglycemia (no DM + A1c<5.7%). Cancer incidence was defined by ICD-9CM codes 140-209.3 or 230-234.9 as an admitting or principal diagnosis. Overall cancer incidence among NHANES participants over 65 years and in Medicare was 25.7 per 1000 person years. There was no significant difference in unadjusted cancer incidence by glucose status (Table). In adjusted proportional hazards models, there was no significant increased risk of cancer incidence for any group compared to the normoglycemia group. These results do not suggest an increased risk of cancer incidence among the older adult Medicare population regardless of elevated glucose status. & For author disclosure information, see page 829. A390 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—DIABETES COMPLICATIONS Adults with cancer diagnosed during follow-up, unweighted n Cancer incidence, all sites (per 1000 person-years) Relative hazard (95% CI), adjusted for age, sex, race/ethnicity, education, and survey period 25.7 (23.1-28.3) -- 24.8 (21.6-27.9) 1.00 (reference) 27.0 (23.1-30.9) 1.14 (0.94-1.37) & 30.0 24.8 (20.8-39.2) (17.5-32.0) 1.17 1.05 (0.82-1.65) (0.77-1.44) 1500-P Stroke Incidence and its Long-Term Impact on Mortality in a Population-Based Cohort With Newly Diagnosed Diabetes and Impaired Glucose Tolerance in China: The Daqing Diabetes Study 1498-P YALI AN, PING ZHANG, JINPING WANG, EDWARD GREGG, BO ZHANG, HUI LI, QIUHONG GONG, YANYAN CHEN, XIAOYAN XING, MICHAEL ENGELGAU, GOJKA ROGLIC, YINGHUA HU, PETER H. BENNETT, GUANGWEI LI, Beijing, China, Atlanta, GA, Daqing, China, Geneva, Switzerland, Phoenix, AZ Low Bone Mineral Density (BMD) Is Associated With Insulin Resistance and Poor Metabolic Profiles: Role of Body Fat and Osteocalcin (OST) ANNY H. XIANG, ZANGHUA CHEN, MARY HELEN BLACK, MIWA TAKAYANAGI, THOMAS A. BUCHANAN, RICHARD M. WATANABE, Pasadena, CA, Los Angeles, CA While stroke is a leading cause of death in China and the numbers of persons with diabetes and impaired glucose tolerance (IGT) are large and growing, the incidence and risk of death attributable to stroke among Chinese adults with these conditions have not previously been quantified. We examined incidence of stroke and related mortality over a 23 year period in a cohort of 630 persons with newly diagnosed diabetes (NDM), 576 with IGT, and 519 with normal glucose tolerance (NGT), who were identified initially in 1986 by screening 50% of the community aged 25 years and over in Da Qing, China. Stroke incidence and related mortality were ascertained up to December 31st, 2009 in some 95% of the cohort. Stroke, fatal or non-fatal, occurred in 218 (36.8%) persons with NDM, 177 (32.7%) with IGT and 121 (24.6%) with NGT. Stroke incidence was higher in men than in women with NDM (29.0 vs. 18.5/1000 person-years) and IGT (22.1 vs. 13.7/1000 person-years), but not with NGT (12.9 vs. 11.4/1000 person-years). The age-adjusted hazard ratios for NDM vs. NGT were 2.15 (95% CI 1.59-2.92) in men and 1.47(95% CI 1.05-2.08) in women. Among those who developed a stroke, death occurred in 145 (66.5%) with NDM, 82 (46.3%) with IGT, and 36 (29.8%) with NGT. Case-fatality rates from stroke (per 1000 person-years) were 130.6 in men and 153.9 in women with NDM, 95.5 and 56.7 in men and women with IGT, and 56.4 and 46.6 in men and women with NGT. Age- and sex- adjusted case-fatality rate ratios were 2.42 (95% CI 1.67-3.69) for NDM vs. NGT and 1.54 (95% CI 1.04-2.29) for IGT vs. NGT. In China, diabetes and IGT lead to considerable excess risk for stroke and excess mortality due to stroke. Persons with diabetes or IGT face double jeopardy by having both a higher stroke incidence and a higher case-fatality rate after a stroke. . Bone has emerged as an endocrine organ and may play a role in glucose homeostasis partially through fat and OST. We tested whether BMD is associated with metabolic parameters in 1239 subjects from the BetaGene study. Phenotyping included BMD and percent body fat (%BF) by DXA, fasting and 2-hr glucose and insulin, delta 30min insulin (ΔIns30), insulin sensitivity (SI) and acute insulin response (AIR) assessed by oral- (OGTT) and intravenous- (FSIGT) glucose tolerance tests. Carboxylated and uncarboxylated osteocalcin (cOST, uOST) were measured in a subset of 729 subjects. The cohort had mean+SD age of 35+8 years and BMI of 29.5+5.9 kg/m2, and fasting glucose ≤126 mg/dl; 73% were female. After adjustment for age, sex, height and weight (to remove weight bearing effects), BMD was positively associated with SI (p=0.0004), negatively associated with %BF, waist circumference, 2-hr glucose, fasting and 2-hr insulin, ΔIns30 and AIR (all p<0.01). Adjustment for %BF reduced the BMD correlations with SI by 44%, 2-hr glucose by 19%, fasting and 2-hr insulin by 11% and 47%, ΔIns30 by 22% and AIR by 33%. Adjustment for %BF did not eliminate the significant associations (adjusted p <0.048). Further adjustment for cOST insignificantly altered the correlations <±5% in the subset with OST. Adjustment for uOST reduced the BMD correlations with ΔIns30 by 18% and AIR by 34%, but only changed the BMD correlations modestly for SI, 2-hr glucose, fasting and 2-hr insulin (6%, -16%, 7%, 9%, respectively). Directions of observed associations were consistent between males and females. Thus, our results indicate that low BMD is associated with insulin resistance and poor metabolic profiles in Mexican Americans without overt diabetes. %BF explained nearly half of the associations for insulin resistance and 2-hr insulin, suggesting some of the effect on BMD may be mediated through body fat. uOST, not the cOST, appears to play a role for the relationship between BMD and acute insulin response. 1501-P Supported by: NIH/NIDDK (5RO1DK-61628) & Duration of Type 2 Diabetes, Independent of Age and Metabolic Status, Is a Predictor of Global Cognitive Decline 1499-P DIVYA YOGI-MORREN, SARAH STRANJFORD, LAURENCE KENNEDY, MARWAN HAMATY, JOHN P. KIRWAN, JOHN GUNSTAD, SANGEETA R. KASHYAP, Cleveland, OH, Kent, OH Physical Functioning and Mortality in Type 2 Diabetes: Insights from TRIAD KELLY R. YLITALO, LAURA MCEWEN, PEARL LEE, ANDREW J. KARTER, WILLIAM H. HERMAN, Ann Arbor, MI, Oakland, CA Clinical studies have noted a greater prevalence of global cognitive impairment, incidence of cognitive decline and Alzheimer’s disease in type 2 diabetes (T2D). The clinical factors that underlie cognitive decline in T2D are not well understood. We performed a prospective, longitudinal cohort study in which 47 adults with T2D (58.0±12 years, 59.6% female, BMI 34.5±9 kg/ m2, HbA1c 7.4±0.7%, T2D duration 11.2±9y, 40% insulin users) and age and gender-matched, healthy non-diabetic subjects (no comorbidities/no medications) completed the Webneuro computerized cognitive test battery, which assesses executive function, attention and memory. Tests were performed at baseline and at follow up within 1 yr to determine the impact of Metabolic Syndrome and its management on cognitive function outcomes.Each clinic visit documented historical data, physical parameters, and biochemical data. At baseline, cognitive impairment was common in the T2D patients, with 13% exhibiting impairment (greater than 1 SD below control performance) in memory, 50% in attention, and 35% in executive function. Partial correlations between years of diabetes and test performance were performed adjusting for demographics and clinical characteristics (laboratory levels of HbA1c, triglycerides, LDL, diagnosis of hypertension, and BMI). Results showed Diabetes is a risk factor for mortality. Subjective health status, including self-reported physical functioning, may also be a marker for mortality. This study examined the association between self-reported physical functioning and mortality in people with diabetes, and determined if this association differed by race/ethnicity. We studied 7,894 type 2 diabetic patients who participated in Translating Research Into Action for Diabetes (TRIAD), a prospective study of diabetes care in managed care. At baseline in 2000, participants completed a questionnaire and had medical record reviews. Physical functioning was assessed with the Short Form Health Survey (SF-12). The National Death Index was searched annually for deaths over 10 years of follow-up (2000-2009). At baseline, mean age was 61.7 years, 50% were non-Hispanic white, 22% were black, and 16% of participants reported “good physical functioning” (better than norms for U.S. adults). Over 10 years, 28% of participants died (2,111/7,894); 39% (856/2,111) due to cardiovascular disease. Relative to those with good functioning, those with poor physical functioning had a 37% higher all-cause death rate, after adjusting for age, sex, race/ethnicity, education, income, body mass ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A391 POSTERS n, unweighted Person-years, mean (95% CI) Follow-up person-years, median (IQR) index, smoking, and comorbidities (Hazard Ratio (HR)=1.37; 95% Confidence Interval (CI): 1.15, 1.63). Similarly, those with poor physical functioning had a 42% higher adjusted cardiovascular death rate compared to those with good functioning (HR= 1.42; 95% CI: 1.06, 1.90). Although blacks were less likely than whites to report good functioning (p<0.01), the association between functioning and mortality was consistent across race/ethnicity. In this managed care population with diabetes, self-reported physical functioning was a robust predictor of mortality, in addition to traditional biological risk factors, for all race/ethnic groups. Physical functioning assessments are easy to perform and may be useful benchmarks for tailoring the care of persons with chronic disease. Normoglycemia Prediabetes Untreated DM Treated DM 2231 1294 358 669 8.2 8.0 7.9 5.8 (7.8-8.6) (7.6-8.4) (7.1-8.6) (5.4-6.3) 7.0 6.9 6.8 5.0 (4.3-12.2) (4.2-11.9) (3.8-11.3) (3.2-7.6) 470 270 80 92 Epidemiology/ Genetics Total 4552 7.8 (7.5-8.2) 6.7 (4.0-11.3) 912 EPIDEMIOLOGY—DIABETES COMPLICATIONS longer duration of diabetes was associated with poorer performance on basic attention (Digit Span, r=-0.41 p<0.04), working memory (Working Memory, r=-0.40, p<0.04), and executive function (Switching of AttentionLetter/Number, r=0.41, p<0.04). We conclude that executive function and attention impairments characterize cognitive decline in middle aged adults withT2D compared to age and gender matched controls. Duration of diabetes is a predictor of cognitive dysfunction independent of metabolic factors and age. Alternative strategies for diabetes education in the population are warranted. than one quarter or no assigned NAqt than among those with full NAqt (HR=1.3, 95% CI 1.1-1.6 and HR=1.2, 95% CI 1.1-1.4, respectively) and similar in those with at least one quarter NAqt. Survival among NA with diabetes on hemodialysis is positively associated with NAqt. Those with less than onequarter NAqt have the lowest median survival time among NA. 1502-P LIZHENG SHI, XIN YE, MEI LU, ERIC Q. WU, HARI SHARMA, DARREN THOMASON, VIVIAN FONSECA, New Orleans, LA, Parsippany, NJ, Boston, MA 1504-P Long-Term Clinical Outcomes Associated With LDL-C and HbA1c Goal Achievement in Patients With Type 2 Diabetes Mellitus (T2DM) Management of Comorbid Type 2 Diabetes and Low Testosterone in Primary Care (UK) There may be incremental clinical benefits associated with dual-goal achievement (hemoglobin (HbA1c) <7% and LDL-cholesterol (LDL-C) <100mg/ dL) in T2DM patients compared with single-goal achievement. Adult T2DM patients with ≥2 measurements of LDL-C and HbA1c were identified from the South Central Veterans Affairs Health Care Network (01/2004-06/2010). Multivariate Cox proportional hazards models were used to evaluate time to the first clinical event associated with time-varying goal achievement status. Clinical events included composite endpoint of microvascular complications (retinopathy, nephropathy, or neuropathy), cardiovascular endpoint (cardiovascular death, stroke, or myocardial infarction), and acute coronary syndromes (ACS), as well as surgical procedures (percutaneous coronary intervention and coronary artery bypass graft (CABG)). A total of 75,646 patients were included (median follow-up: 4.5 years). Compared with only LDL-C goal achievement, dual-goal achievement was associated with lower risks of microvascular complications, ACS, and surgical procedures. Compared with only HbA1c goal achievement, dual-goal achievement was associated with lower risks of cardiovascular endpoint and CABG. In this analysis of US Veterans with T2DM, dual-goal achievement was associated with incremental clinical benefits compared with only HbA1c or only LDL-C goal achievement. POSTERS Epidemiology/ Genetics STEPHAN LANES, BRADLEY H. CURTIS, CHARLES WENTWORTH, KRISTINA BOYE, CINIRA LEFEVRE, MELISSA GAWLIK, DARA SCHUSTER, GLENN MATFIN, Lexington, MA, Indianapolis, IN, Windlesham, United Kingdom, Minneapolis, MN While the increased prevalence of low testosterone (LT) in men with type 2 diabetes (T2DM) is well established, uncertainty exists regarding the interrelationship between these two conditions (causal or association). This retrospective cohort study utilized the validated Clinical Practice Research Database (CPRD) a UK primary care electronic health record database. We obtained detailed files for males with clinically diagnosed LT or T2DM containing all medical records available from the primary care physician (GP). Data (2000-2010) were examined for baseline characteristics including labs, allowing calculation of incidence of LT according to prior T2DM or vice versa. Patients were included in the incident T2DM and LT cohorts if they had no history of diagnosis of the condition prior to a 1-year enrollment index date. We identified 75,772 men with incident T2DM (Mean Age 62; BMI 31) and 20,509 men with incident LT (Mean Age 36; BMI 29) of a total evaluable population of approximately 3.5m men. In men with T2DM, incidence of clinical LT was 1.72 times (95% CI 1.59, 1.86) greater than the incidence in those without T2DM; whereas prevalent LT did not predict an increased risk of developing T2DM; RR 0.94 (95% CI 0.90, 0.98). Only 1% of patients with T2DM had a total testosterone test. Among men with newly diagnosed LT, 12% had a testosterone test in the year prior to diagnosis and 29% had a testosterone test in the year following diagnosis. In addition, 4,488 (< 25%) of incident LT patients received testosterone replacement treatment (TRT) during the study period. In the UK primary care setting, clinical LT occurred nearly twice as frequently among patients with T2DM, even in the setting of extremely low screening rates. In addition, appropriate TRT and monitoring of testosterone levels after LT diagnosis was also low, indicating a gap between current guidelines and practice. Given the potential for improved quality of life with LT treatment, education of men with T2DM and the GP on the comorbid nature of T2DM and LT is warranted. Supported by: Daiichi Sankyo, Inc. 1505-P The 9p21 Myocardial Infarction High Risk Locus Does Not Associate With Peripheral Vascular Disease in Patients With Type 2 Diabetes Mellitus Supported by: Eli Lilly and Company 1503-P MEDA E. PAVKOV, NILKA R. BURROWS, PYONE CHO, KAI M. BULLARD, PAUL W. EGGERS, ANDREW S. NARVA, Atlanta, GA, Bethesda, MD ELEONORA RUSSO, DANIELA LUCCHESI, LAURA PUCCI, SALVATORE DE COSMO, MONIA GAROFOLO, VERONICA SANCHO BORNEZ, SIMONA GEORGIANA POPA, ROSSELLA RUSSO, ROBERTO MICCOLI, VINCENZO TRISCHITTA, GIUSEPPE PENNO, STEFANO DEL PRATO, Pisa, Italy, San Giovanni Rotondo, Italy, Craiova, Romania Diabetes is the leading cause of kidney failure among Native Americans (NA), however, those NA treated with dialysis have better survival than other racial/ethnic groups. We analyzed records from the US Renal Data System with hemodialysis initiated in 1995-2009 to assess survival among NA with diabetes listed as the primary cause of kidney failure. Kaplan-Meier method was used to compare survival by NA blood quantum (NAqt), and Cox regression analysis to compute adjusted hazard ratios (HR) for death due to any cause. The study included 5,635 persons of which 60% had full NAqt, 20% had less than full but greater than half NAqt, 5% had one quarter to half NAqt, 3% had less than one quarter NAqt, and 12% reported NA ancestry but had no blood quantum information in the Indian Health Service database. Median follow-up time was 3.6 years (interquartile range 1.5 to 6.2 years). Median survival time was less with lower NAqt: 4.6 years (95% CI 4.4-4.7 years) in those with full NAqt to 3.2 years (95% CI 2.5-3.5) in those with <25% NAqt, and 2.8 years (95% CI 2.5-3.1) in those without assigned NAqt (p <0.001). Compared with hemodialysis patients with full NAqt, unadjusted HR of death was 1.1 (95% CI 1.02-1.3), 1.2 (95% CI 1.01-1.4), 1.3 (95% CI 1.1-1.6), and 1.3 (95% CI 1.1-1.5) in those with lesser or no assigned NAqt, respectively. After controlling for demographic factors, comorbidities, health insurance status, smoking, and erythropoetin treatment in a Cox regression analysis, the risk of death remained higher in those with less Chr9p21 locus is a robust CHD genetic marker. Associations were reported with carotid artery plaque, stroke, aneurysms, heart failure, CVD mortality, while no association was found between Chr9p21 and CV risk factors, suggesting that the locus exerts a direct effect on CV risk. We explored the association between the Chr9p21 (SNP rs2383206) and ABI and peripheral artery disease (PAD, i.e. ABI <0.9) in 937 unrelated Italian T2DM (M/F 550, 58.7%/387, 41.3%). Genotyping was performed by TaqMan assay implemented on HT7900 Applied Biosystems platform. Patients were 59.2±7.5 yrs old with a diabetes duration (DD) of 10.4±9.0 yrs, BMI 29.4±5.4 kg/m2; sBP 142±19, dBP 82±10 mmHg, HbA1c 7.7±2.7% (median value 7.45%; first and third quartiles 6.75 and 8.25%); 132 patients (14.1%) had PAD. Genotype distribution was: AA (n. 146) 15.6%; GA (n. 452) 48.2%; GG (n. 339) 36.2%. The sample was in Hardy-Weinberg equilibrium. There was no difference among genotypes in age, DD, smoking, BMI, sBP, dBP, HbA1c, total-, LDL- and HDL-C, triglycerides, uric acid, fibrinogen, urinary A/C ratio and eGFR (MDRD). No association was found between rs2383206 and ABI as a continuous trait (AA: 1.06±0.19; GA: 1.05±0.17; GG: 1.04±0.16; p=NS). Furthermore, no association was apparent between rs2383206 and PAD prevalence (AA 15.1%; GA 13.5%; GG 14.5%; p=0.867). No interaction was observed between rs2383206 and HbA1c above the median value or within the fourth quartile. No differences emerged between genders or in Survival on Dialysis among Native Americans With Diabetes by Level of Indian Ancestry, United States, 1995–2010 & For author disclosure information, see page 829. A392 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—DIABETES COMPLICATIONS subjects with vs. those without family history of CHD. In logistic backward regressions, PAD was associated with age, sBP, smoking (p<0.0001 for all), dBP (inversely), male gender (p=0.001 for both), HbA1c (p=0.022) and A/C ratio (p=0.035) (model 1) or CHD (p<0.001) (model 2), but not to rs2383206. In this cohort of Italian T2DM, the rs2383206 SNP, previously associated with CHD and shown to interact with glycaemic control, was not associated with continuous ABI and PAD phenotypes. Among PWD, a disproportionate percent of Black (41%), low income (48%), less educated (44%) and not insured (48%) had significant tooth loss compared to White (30%), high income (11%), highly educated (14%) and insured (27%). Oral treatment decreased with lack of insurance and reduced education or income level. Serious dental issues occur even among PWD who seek regular oral health treatment and indicate a need to communicate the importance of proper oral health care to PWD. 1506-P Adiponectin and Retinopathy in Type 1 Diabetes Odds Ratios (OR) and (95% Wald Confidence Intervals) for DR Severity Characteristic Model 1 Model 2 Model 3 Model 4 Age at exam, 0.99 1.01 1.00 0.99 per 1 yr (0.96-1.02) (0.98-1.05) (0.97-1.04) (0.96-1.03) Male 1.78 2.21 1.72 1.50 (1.13-2.81) (1.35-3.62) (1.01-2.93) (0.87-2.61) Log 9-20 yr ADPN, 1.79 1.58 1.74 1.55 per 1 unit (1.21-2.65) (1.04-2.40) (1.13-2.66) (1.00-2.41) Mean HbA1c,per 1% 3.18 2.95 2.99 (2.45-4.11) (2.27-3.84) (2.29-3.90) eGDR, 0.80 0.86 per1 mg · kg-1 · min-1 (0.70-0.93) (0.74-1.00) Systolic BP, 1.09 per 3 mmHg (1.02-1.16) Log UACR, per 1 unit Model 5 1.00 (0.96-1.03) 1.68 (0.99-2.84) 1.44 (0.94-2.20) 3.13 (2.41-4.06) 1508-P Handgrip Strength Is Associated With Glomerular Filtration Rate in Patients With Diabetes Type 2 PATRICIO LOPEZ-JARAMILLO, DANIEL COHEN, DIEGO GOMEZ-ARBELAEZ, HERTZEL GERSTEIN, JACKIE BOSCH, SALIM YUSUF, ORIGIN INVESTIGATORS, Bucaramanga, Colombia, Hamilton, ON, Canada Deterioration of renal function is a common complication of diabetes type 2 (DM2). Grip strength (GS) is associated with better renal function and lower mortality in individuals with chronic kidney disease. DM2 patients are a group at risk of strength deficits since lower strength predicts Insulin resistance and the onset of DM2, in turn are associated with the deterioration of muscle function and strength. The association between strength and renal function in DM2 has not been evaluated. In a subanalysis of the ORIGIN trial of CVD outcomes and mortality in DM2 and pre DM2, we examined the association between GS and estimated glomerular filtration rate (eGFR). GS was assessed and eGFR was determined using the MDRD formula in 12516 patients (35% female), mean age 63.6 (±7.8) with either impaired glucose tolerance/impaired fasting glucose (12%), or DM2 (88%),. Significant trends (P<0.001) consistent with a positive relationship between eGFR (mL/ min) and age adjusted GS quintiles (GSa), were noted for males and females separately (fig.1). We found a graded association between strength and an important marker of renal function in an international cohort of Pre DM2 and DM2 patients. Our analysis cannot determine causality, but strength or strength training interventions are associated with better endothelial function, inflammatory profile and insulin sensitivity pathways and lower oxidative stress, factors which may mediate positive associations with renal function. Model 6 1.02 (0.98-1.05) 2.50 (1.48-4.20) 1.31 (0.85-2.03) 2.56 (1.95-3.37) 1.11 (1.04-1.18) 1.82 (1.43-2.32) Supported by: NIDDK (R01DK36904) 1507-P Gum Disease and Diabetes in Michigan, an Overlooked Connection H.C. MICHELLE BYRD, CHRIS FUSSMAN, DAWN L. CRANE, BETH ANDERSON, SARAH LYON-CALLO, Lansing, MI Diabetes increases the susceptible to oral health diseases like periodontitis which can lead tooth loss and bone disease. We report the prevalence of oral health treatment and outcome among adult persons with diabetes (PWD) based on results from the 2008 and 2010 Michigan Behavioral Risk Factor Surveys (MiBRFS). Questions related to oral health, diabetes, and behavioral factors were included within the 2008 and 2010 MiBRFS. The diabetes definition excluded prediabetes or gestational diabetes. Questions included oral health treatment (dental visit and cleaning), teeth missing due to infection, and dental coverage. Prevalence of significant tooth loss was statistically higher among PWD vs. persons without for all ages (Figure 1). Despite similar oral health treatment compliance, this prevalence among PWD age 18-44 was 4 times higher than those without diabetes. Older PWD tended to have oral health treatment less often and a higher percent of significant tooth loss than those without diabetes. ADA-Funded Research & Supported by: Sanofi (NCT00069784) For author disclosure information, see page 829. Guided Audio Tour poster A393 POSTERS The role of adiponectin (ADPN) in type 1 diabetes (T1DM) complications is unclear and few studies have examined the relationship between retinopathy (DR) and prospectively measured ADPN. The Wisconsin Diabetes Registry Study cohort, followed since T1DM diagnosis through 20 years, provided this opportunity. Subjects with DR grading by fundus photographs at the 20-year exam and ADPN tested in -80oC stored samples from 1, 4, 7, 9 or 20-year exams were included. Twenty-year examinees (n=304) participated in (mean) 3.43 total exams yielding 1043 stored plasma samples tested and 99% (n=301) had 20-year DR grading. The relationship between ADPN and DR by 20 years was assessed by ordinal logistic regression of DR severity categories: none-minimal, mild-moderate and vision-threatening DR, and logistic regression of a dichotomous (yes/no) indicator of progression from 4 or 9 to 20 years. Mean ADPN levels at 1-4, 7-9 and 9-20 years, and overall, were investigated. A positive relationship between higher ADPN during 9-20 years diabetes and 20-year severity was no longer significant when systolic BP or urine albumin-creatinine ratio at 20 years were considered. Unadjusted mean ADPN at earlier durations was not significantly related to DR severity or progression. Higher ADPN at later diabetes coincides with DR severity, kidney function and higher BP at 20 years diabetes duration. Our findings support a possible compensatory response of increased ADPN tied to endothelial dysfunction- or inflammation-based processes. Epidemiology/ Genetics TAMARA J. LECAIRE, MARI PALTA, RONALD KLEIN, BARBARA E.K. KLEIN, Madison, WI POSTERS Epidemiology/ Genetics EPIDEMIOLOGY—DIABETES COMPLICATIONS 1509-P 1511-P Characterization of the Risk for Urinary Tract Infections in Patients With Type 2 Diabetes Disease Burden of Urinary Tract Infections among Type 2 Diabetes Mellitus (T2DM) Patients: A U.S. Database Study KRISTY IGLAY, ALEX Z. FU, YING QIU, SAMUEL S. ENGEL, RAVI SHANKAR, MICHAEL J. DAVIES, KIMBERLY G. BRODOVICZ, Whitehouse Station, NJ, Washington, DC SHENGSHENG YU, ALEX Z. FU, YING QIU, SAMUEL S. ENGEL, RAVI SHANKAR, SWAPNIL RAJPATHAK, LARRY RADICAN, KIMBERLY G. BRODOVICZ, Whitehouse Station, NJ, Washington, DC, North Wales, PA Type 2 diabetes (T2DM) is associated with increased rates of infections, with urinary tract infections (UTI) among the most commonly encountered. The incidence and risk of UTI in patients (pts) with or without T2DM were assessed in a retrospective US cohort study. Pts ≥18 years old with a T2DM diagnosis in 2010 were identified using the MarketScan database. Index date was first date with diagnosis in 2010. Pts were excluded if they had T2DM diagnosis or antihyperglycemic medication use in the year prior to index date. Pts without T2DM were matched on age, gender, index date, and geographic region. Eligible pts had medical records for 1 year before (baseline) and after (follow up) the index date. UTI diagnosis (UTI, cystitis, and pyelonephritis) during follow up was assessed using ICD-9 codes. Logistic regression adjusted for patient characteristics and comorbid conditions was used to assess the likelihood of experiencing UTI. A total of 89,790 matched pairs were selected. The mean age at index date was 56 years and 51% were male. Pts with T2DM had more pre-existing comorbid conditions compared to pts without T2DM. In the 1-yr follow up, 7.6% of all pts were diagnosed with UTI, with more pts with T2DM compared to those without T2DM (9.4% vs. 5.7%; p<0.0001). The proportion of women with T2DM experiencing UTI was greater than those without T2DM (14.0% vs. 9.1%; p<0.0001). A lower proportion of men had UTI, but the difference between T2DM and no T2DM was significant (5.0% vs. 2.4%; p<0.0001). In a logistic regression, pts with T2DM had a greater likelihood of experiencing UTI during follow up (adjusted odds ratio [OR] = 1.54 [95% CI 1.47, 1.60]; p<0.0001). When stratified for gender, the odds were still significantly greater for pts with T2DM (women: OR = 1.43 [1.36, 1.50]; men: OR = 1.91 [1.76, 2.07]; p<0.0001 for both). Recurrence of UTI was also higher with T2DM (1.6% vs. 0.6%; p<0.0001) during follow up. In conclusion, pts with T2DM were more likely to experience a UTI and recurrent UTIs compared to pts without T2DM. While the association between type 2 diabetes mellitus (T2DM) and urinary tract infection (UTI) is known, the economic burden has not been adequately quantified. Healthcare resource utilization and costs for T2DM patients with (prevalent cohort [PC]) and without (incident cohort [IC]) a history of UTI were assessed in a retrospective cohort study using a US commercial health insurance claims database (MarketScan). T2DM patients aged ≥18 years with continuous enrollment for ≥1 year prior to, and after, the first observed T2DM diagnosis (between 1/1/2009-9/30/2010) were included. Patients with type 1 diabetes or gestational (including pregnancy) or other forms of secondary diabetes were excluded. Cases of UTI, cystitis, and pyelonephritis were identified using ICD-9 codes. The final study cohort comprised 93,919 T2DM patients. UTI prevalence was 7.6% (n=7,143) and 8.3% (n=7,835) at baseline and at the end of the follow-up, respectively. During the follow-up period, 33.9% of the PC had ≥1 UTI while 6.2% of the IC had ≥1 UTI (p<0.0001). After controlling for patient characteristics and baseline comorbidities, age 75+ (odds ratio [OR]=1.36 vs. age 55-64, [95% CI: 1.26, 1.47]), female gender (OR=2.9, [2.75, 3.06]), and history of UTI (OR=5.81, [5.48, 6.15]) were the strongest predictors of UTI. Compared to the IC, the PC was more likely to have UTI related inpatient visits (11.4% vs. 9.8%, p=0.038), outpatient visits (96.9% vs. 95.2%, p=0.0005), and more outpatient visits per patient (2.60 vs. 1.62, p<0.0001). The associated outpatient cost per patient per year was also higher for the PC than IC ($630.8 vs. $415.9, p=0.001 for payers, $62.92 vs. $48.54, p=0.0006 for patients). There was no significant difference in inpatient cost for either payers or patients. In conclusion, among T2DM patients, UTI was associated with increased healthcare utilization and higher costs, especially for those with previous UTI. 1512-P Differential Expression of IRS-1 in Visceral and Subcutaneous Adipose Depots in Morbidly Obese/Type 2 Diabetic Subjects: Their Correlation With Biochemical Profile With 2 Novel Variations Sequenced in Asian Indians 1510-P Treatment Gaps in Chinese Type 2 Diabetes Patients With Chronic Kidney Disease: The Joint Asia Diabetes Evaluation (JADE) Program MUKTI SHARMA, KALPANA LUTHRA, SANDEEP AGGARWAL, ANOOP MISRA, NAVAL VIKRAM, New Delhi, India ROSEANNE O. YEUNG, YUYING ZHANG, RISA OZAKI, ANDREA O. LUK, NICOLA BROWN, YI SUI, YU CHEUNG, KAM PIU LAU, CHIU CHI TSANG, W.B. CHAN, HARRIET CHUNG, REBECCA WONG, ALICE P.S. KONG, RONALD C. MA, FRANCIS C. CHOW, PETER TONG, JULIANA C. CHAN, WING-YEE SO, HONG KONG JADE STUDY GROUP, Hong Kong, China To look for differential expression of IRS-1at regional fat-depots (visceral and subcutaneous) in morbidly obese diabetic patients, and correlate genotype-phenotype traits if any in above subjects. A total of 35 morbidly obese (BMI>40Kg/m2) in presence of co-morbidities and 16 controls (BMI<25Kg/m2) adipose tissue were obtained from subjects undergoing Bariatric and elective abdominal surgery respectively. RealTime qPCR performed for gene expression. Biochemical parameters were assessed. Sequencing of IRS-1in morbid obese/diabetic subjects along with controls was carried out to identify novel variations. We observed a decrease in mRNA expression of IRS-1in adipose tissue of visceral and subcutaneous depots in morbidly obese subjects than controls (non-obese), with a marked reduction in visceral as compared to subcutaneous adipose tissue of morbidly obese diabetic subjects (p=0.02). A salient finding of this study was presence of two novel variations, not reported previously: one, in codon 1102 GAG>AAG, a non-synonymous mutation, encoding lysine instead glutamate in morbidly obese subjects with insulin resistance, second a deletion at codon 658 in three morbidly obese/ insulin resistant and one non-obese with high levels of insulin (Accession numbers: JX912162, JX912163, JX901287, JX901288, JX901289). Our observation of a substantial reduction in expression ofIRS-1in visceral and subcutaneous adipose tissues of morbidly obese diabetic subjects, strongly suggest that the IRS-1expression may serve as a novel molecular marker for predicting tissue insulin responsiveness. Novel variations at codons 658 and 1102 of IRS-1 were present only in morbidly obese, insulin resistant subjects, suggesting their crucial role in insulin resistance and obesity in these subjects and need to be functionally characterized. CKD amplifies the risk of cardiovascular disease (CVD) although control of risk factors can reduce the risk of morbidity and mortality in these patients. The JADE Program is a quality improvement (QI) initiative, augmented by a web-based program with decision support protocols, validated risk engine, and personalized diabetes feedback reports. Between 2007-2012, 15314 patients were enrolled from 6 hospital and community clinics in Hong Kong. In this cross-sectional cohort, 9.2% (95% CI:8.7-9.7) had at least stage 3 CKD and were more likely to be female (49.1 vs. 45.2%), older (69.0±10.1 vs. 58.2±11.1yrs), with a longer disease duration (median 7 vs. 6yrs). CKD patients had higher A1C (7.8±1.7 vs. 7.5±1.5%, P<0.001), systolic blood pressure (BP) (146±22 vs. 134±18 mmHg, P<0.001), and lower LDL-C (2.5±0.9 vs. 2.6±0.8 mmol/L, P<0.001). CKD patients were more likely treated with insulin (19.4 vs. 8.9%), statins (60.4 vs. 38.3%) and renin-angiotensin inhibitors (55.2 vs. 35.9%). They also had higher rates of CVD (22.6 vs. 9.2%), stroke (15.3 vs. 5.8%), peripheral vascular disease (16.3 vs. 3.4%), retinopathy (44.4 vs. 25.3%), and neuropathy (12.5 vs. 3.6%) (all P<0.001).Patients with CKD were less likely to reach target A1C (36.0 vs. 43.7%) and BP (21.3 vs 36.6%), but more likely to reach target LDL (60.5 vs. 49.5%) (all P<0.001). Up to 2012, 280 CKD patients had undergone repeat assessment, of which LDL target <2.6mmol/L achievement improved from 58.4% to 67.6% with absolute LDL falling from 2.5±0.9 to 2.3±0.9mmol/L and HDL increased from 1.1±0.3 to 1.23±0.4 mmol/L (all P<0.001) after a follow up time of 1.5±0.5 years. We did not detect any significant changes in A1C or BP in these patients. Our findings highlight the treatment gaps in these high risk CKD patients, which can be detected using a structured, integrated care program in a high-volume clinic setting, and provide useful information for future QI implementation Supported by: Dept. of Biotechnology (N-881) Supported by: Asia Diabetes Foundation & For author disclosure information, see page 829. A394 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—DIABETES COMPLICATIONS in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight. 1513-P Kidney Failure and Diabetes Mellitus Related Hospital Admissions in California: 2000–2010 1515-P KALANI S. RATNASIRI, Davis, CA The aim of this study was to determine prevalences of diabetes mellitus (DM) and concurrent kidney failure (KF) (acute, chronic and unspecified) among people (> 20 years) admitted to hospitals in California from 2000 to 2010. The analysis was undertaken on the hospital data compiled by the California Office of Statewide Health Planning and Development (OSHPD). Diagnoses of > 32.3 million de-identified hospital admissions recorded in the OSHPD database were screened, employing ICD9CM codes specific to DM (as primary or any listed diagnosis) and KF. Trends were evaluated using regression models. The prevalence of DM among hospital admissions (as primary or any listed diagnosis) increased significantly from 16.6% in 2000 to 24.7 % in 2010, an increase of 48.7%. After adjusting for covariates (gender, age, race/ethnicity, payer source), DM related admissions had increased by 55.0% from 2000 to 2010 (odds ratio 1.55 [95% CI 1.54 - 1.56]). The prevalence of KF among hospital admissions (as primary or any listed diagnosis) increased significantly from 3.9 % in 2000 to 16.7 % in 2010, a 3.3 fold increase. After adjusting for covariates (as above) this increase was 4.8 fold [4.80 - 4.87]. Among admissions for DM, the unadjusted prevalences of KF were 9.7 % and 34.1% which was a 3.5 fold increase. These data suggest that between 2000 and 2010 there have been significant increases in the number of admissions with both DM and KF with a disproportionate increase in the latter. Prevalence of Metabolic Syndrome (MetS) and Associated Co-Morbidities in Hong Kong Chinese Patients With Type 2 Diabetes: The Joint Asia Diabetes Evaluation (JADE) Program Supported by: Asia Diabetes Foundation 1514-P 1516-P Association between Diabetes, Diabetes Treatment and Endometrial Cancer Role of Serum Immunoglobulin G (IgG) Antibody against Periodontal Bacteria in Type 2 Diabetes and Pre-Diabetes JUHUA LUO, KAREN MARGOLIS, LEWIS KULLER, ROWAN CHLEBOWSKI, JEAN WACTAWSKI-WENDE, SHIRLEY BERESFORD, CHU CHEN, LORENA GARCIA, MICHAEL REGIER, Bloomington, IN, Minneapolis, MN, Pittsburgh, PA, Los Angeles, CA, Buffalo, NY, Seattle, WA, Davis, CA, Morgantown, WV DEEPIKA SHRESTHA, YOUNHEE CHOI, JIAJIA ZHANG, LINDA J. HAZLETT, ANWAR T. MERCHANT, Columbia, SC, Daegu, Republic of Korea Periodontitis, a chronic low grade, poly-microbial infection of the gums, is associated with diabetes and pre-diabetes but the role of specific periodontal microorganisms is understudied. We evaluated serum IgG antibodies against 19 periodontal bacteria in relation to type2 diabetes (n=990; Mean A1C= 7.6%) and pre-diabetes (n=2059; Mean A1C= 5.9%) in the NHANES III (1988-1994) dataset among 7366 participants aged 40 or more. Four antibody clusters were derived using cluster analysis. Cluster 1 consisted of A. actinomycetemcomitans, T. forsythia, T.denticola, S. noxia, E. corrodens, V. parvula and C. rectus; Cluster 2 of P. intermedia, P. nigrescens, P. melaninogenica, and P. gingivalis mix; Cluster3 of A. naeslundii and E. nodatum and; Cluster4 of S. intermedius, S. oralis, S. mutans, F. nucleatum, M.micros and C. ochracea. In the surveylogistic regression models that included all four clusters, clusters 1 and 3 were not associated with diabetes and pre-diabetes. Cluster 2 was positively associated with diabetes after adjusting for age, sex, education, ethnicity, smoking and drinking alcohol, but not for pre-diabetes. Cluster 4 was inversely related to diabetes and prediabetes, even after adjustment for known confounders. Specific periodontal microorganisms may have qualitatively different associations with diabetes and pre-diabetes and deserve further study. Endometrial cancer is the most common female gynecologic cancer among westernized countries with increasing incidence over the past two decades. A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, the majority of these studies use case-control designs and no epidemiological study has examined the association between metformin treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, metformin treatment and endometrial cancer risk in postmenopausal women participating in the Women’s Health Initiative (WHI) - a large prospective study. A total of 88,107 women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed through September 30,2010. Over a mean of 11 years follow-up, 1,241 endometrial cancers developed. Information on diabetes therapy was collected via a face-to-face review of current medication containers that participants brought to the baseline visit. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer. Compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer. However, these effects were observed only without adjusting for BMI. After further adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. In conclusion, there is no significant association between diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women. Our results suggest that the relationship observed ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A395 POSTERS The JADE Program is an integrated quality improvement initiative augmented by a web-based program with built-in clinical decision support protocols, validated risk stratification engine, and personalized patient feedback reports. Between 2007 and 2012, 15314 patients were enrolled from 6 hospital- and community-based clinics. Of these, 54.2% (95% CI: 53.4%-55.0%) had MetS using the International Diabetes Federation criteria. Compared to non-MetS patients, MetS patients were of similar age (59.9±11.6 vs. 58.3±11.2yrs) but predominantly female (53.0% vs 37.1%), with longer disease duration (9.4±8.2 vs. 8.5± 7.7yrs). The MetS patients were less likely to achieve the A1C goal of <7% (38.0% vs. 48.0%) and had higher A1C (7.66±1.53% vs. 7.37±1.56%) (both P<0.001). Patients with MetS were more likely to be treated with insulin (10.6% vs. 9.0%), statins (44.5% vs. 35.6%) and renin-angiotensin inhibitors (44.2% vs. 30.2%) (all P<0.001). They also had higher rates of coronary events (11.8% vs. 8.9%), stroke (7.9% vs. 5.4%), peripheral vascular disease (5.4% vs. 3.7%), chronic kidney disease (11.8% vs. 6.3%), end stage renal disease (0.9% vs. 0.4%), sensory neuropathy (5.0% vs. 3.7%), retinopathy (28.4% vs. 25.5%) and malignancy (4.7% vs. 4.1%) (P<0.001). As of 2012, 2226 MetS patients have completed a repeat assessment after a mean of 1.3±0.4 years, and demonstrated significant improvements in rates of risk factor target attainment: A1C <7% increased from 39.6% to 42.3% (P=0.014), BP <130/80mmHg increased from 24.6% to 35.2% (P<0.001), and LDL-C <2.6mmol/L increased from 47.3% to 59.4% (P<0.001). Impressively, 21.2% of patients also no longer fulfilled criteria for MetS (P<0.001). Our findings suggest that a structured, integrated care program augmented by information technology improves target attainment in diabetes patients with MetS in a high-volume clinic setting. Epidemiology/ Genetics YUYING ZHANG, ROSEANNE O. YEUNG, RISA OZAKI, ANDREA O. LUK, NICOLA BROWN, YI SUI, YU CHEUNG, KAM PIU LAU, CHIU CHI TSANG, W.B. CHAN, HARRIET CHUNG, REBECCA WONG, ALICE P.S. KONG, RONALD C. MA, FRANCIS C. CHOW, PETER TONG, WING-YEE SO, JULIANA C. CHAN, HONG KONG JADE STUDY GROUP, Hong Kong, China EPIDEMIOLOGY—DIABETES COMPLICATIONS most common sites of infection leading to hospitalization were lower respiratory tract, skin and soft tissue, and urinary tract (Table 1). Comparing with non-diabetic men, diabetic men were associated with significantly increased risks of necrotizing fasciitis, skin and soft tissue, and bone and joint infections. For diabetic women, urinary tract and lower respiratory tract were the most common infection sites. As compared with non-diabetic women, diabetic women were associated with significantly higher risks of necrotizing fasciitis, skin and soft tissue, bone and joint, urinary tract, postoperative clean wound, and septicemia. Despite similar fatality with nondiabetics, diabetic patients had higher hospital cost and length of stay. Association of the serum IgG titers in different clusters in relation to diabetes and pre-diabetes Models DIABETES PRE-DIABETES** Cluster1 Cluster2 Cluster3 Cluster4 Cluster2 Cluster4 Model1:Odds Ratio(95% CI) 1.02 1.08 0.97 0.86 1.01 0.87 P-value (0.98-1.06) (1.04-1.14) (0.92-1.02) (0.79-.93) (0.97-1.05) (0.83-0.92) 0.2763 0.0006 0.2558 <.0001 0.6063 <.0001 Model2:Odds Ratio(95% CI) 0.99 1.05 1 0.92 0.99 0.93 P-value (0.96-1.04) (0.99-1.11) (0.95-1.06) (0.85-.99) (0.95-1.03) (0.88-0.98) 0.9753 0.0554 0.9901 0.0475 0.5335 0.005 Model3:Odds Ratio(95% CI) 0.99 1.06 1 0.92 0.99 0.94 P-value (0.95-1.04) (1.00-1.12) (0.95-1.06) (0.84 -1) (0.96-1.04) (0.89-0.98) 0.8638 0.0248 0.9982 0.0491 0.8547 0.014 Model4:Odds Ratio(95% CI) 1 1.05 0.99 0.88 1 0.94 P-value (0.96-1.03) (1.00-1.11) (0.94-1.05) (0.80-.98) (0.95-1.04) (0.89-0.98) 0.9843 0.0517 0.9478 0.0165 0.963 0.0133 Model1 with no adjustment for confounders; Model 2 adjusted for age (continuous), sex, education, ethnicity; Model3 adjusted further for smoking and drinking alcohol; Model4 further to physical activity, BMI (continuous), waist circumference [WC] and dentist visit. Note:** Cluster 1 and Cluster 3 were insignificant in all four models for pre-diabetes. Supported by: Taiwan Dept. of Health 1517-P 1519-P Celiac Autoimmunity Is Associated With Lower Blood Pressure and Renal Risk in T1D Skin Accumulation of Advanced Glycation End-Products (AGEs) Highly Correlates With Severity of Renal Complications in Patients With Diabetes POSTERS Epidemiology/ Genetics CHRISTINA CRISTALDI, RACHEL G. MILLER, VINCENT C. ARENA, INGRID LIBMAN, YIHE HUANG, DOROTHY J. BECKER, TREVOR J. ORCHARD, Pittsburgh, PA RYO KAWADA, OSAMU HANYU, KAZUO FURUKAWA, MASAHIRO ISHIZAWA, MASAHIKO YAMAMOTO, TAEKO OSAWA, TAKAHO YAMADA, SHINITI MINAGAWA, HIROMI SUZUKI, AYAKO YAMADA, YORIKO HEIZNZA, AKIKO SUZUKI, HIROHITO SONE, Niigata, Japan Though the long-term consequences of undiagnosed celiac disease in individuals with T1D are unclear, celiac disease has been associated with an increased risk of end-stage renal disease (ESRD) independent of T1D. We thus evaluated whether celiac autoimmunity augments the development of microalbuminuria (MA; AER 20-200µg/min) and diabetic nephropathy (DN; AER > 200µg/min) in the 22 year prospective, observational, Pittsburgh Epidemiology of Diabetes Complications (EDC) Study of childhood onset diabetes diagnosed within years 1950-1980 and first examined 1986-88. Serum samples from 451 of the 658 participants have so far been screened for tissue transglutaminase IgA (TTGIgA) antibodies and IgA levels. This sample, when compared to the remaining participants, included more diagnosed with T1D in the years 1950-59. Of these 451, 32 (7.1%) had a positive TTGIgA ≥ 20 units; half of whom (n=16) had a strongly positive TTGIgA (>30 units). There were no differences in diagnosis date of T1D, diabetes duration, age of onset, race, sex, A1C, lipid profile, height, weight, BMI, smoking status, and anti-hypertensive therapy in those with strongly positive versus negative celiac antibodies. The strongly positive group at baseline had a lower systolic blood pressure (106 ± 15 vs 115 ± 17; p=0.03) and 25 year cumulative incidence of DN than those with negative antibodies (17% vs 49%; p=0.04). However, adjustment for blood pressure and year of T1D diagnosis eliminated the statistical significance (p=0.23). None of those with positive celiac serology developed intestinal lymphoma. These results suggest that positive, yet untreated, celiac autoimmunity, in a long term survivor population of older participants with childhood onset T1D, does not increase the risk of MA, DN, or ESRD and may even be associated with lower blood pressure and renal risk after 25 years duration. Further evaluation and screening of remaining participants will help resolve the extent to which these results reflect a survivor bias. Reducing sugars such as glucose react nonenzymatically with protein amino groups to form advanced glycation end products (AGEs). Although the roles of AGEs in the pathogenesis and progression of diabetic vascular complications, dementia, and aging have been studied, the relationship between AGEs and diabetic complications in Asian subjects has been little studied. Accumulation of AGEs on the vascular wall on or under the skin is reported as skin autofluorescence (AF) with a skin AF reader. Skin AF is determined by a spectrometer across the 420-600 nm range on the theforearm. We examined the relationship between skin AF of diabetic patients and biochemical variables or status of vascular complications to clarify factors determining skin AF. Skin AF was measured using the AGE Reader (DiagnOptics, Groningen, Netherlands) in 140 outpatients with diabetes who went to Niigata Univ. Hosp. in 2009-2010. Mean age was 60±13.2 y, HbA1c was 7.9±1.8%, BMI was 24.8±4.7 kg/m2, duration of diabetes was 13.7±10.4 y, and skin AF was 2.6±0.6 arbitrary units. There were significant correlations between skin AF and age (P=0.00), BMI (P=0.29), duration of diabetes (P=0.26), retinopathy stage (P=0.37), nephropathy stage (P=0.001), eGFR (P=0.00), total plaque score (P=0.01), maximum intima-media thickness (P=0.001), and maximum plaque thickness (P=0.005). In multivariate analyses with skin AF as the dependent variable, stage of nephropathy (P=0.007) and eGFR determined (P=0.00) skin AF independently. Stage of retinopathy and ischemic heart disease were not related to skin AF. These results imply that accumulation of AGEs on the vascular wall may be closely related to diabetic nephropathy. In conclusion, the close association between skin AF and diabetic nephropathy seen in this analysis warrants future prospective studies to elucidate whether skin AF could be a predictor of nephropathy and cerebral infarction. Supported by: R01DK034818 1518-P 1520-P Risk of Infection Incidence, Fatality, and Medical Resource Utilization in Adult Diabetic Patients—A Nationwide Study Microalbuminuria: Association With Gray Matter Atrophy in Cognitive Circuits in Type 2 Diabetes CHIA-HSUIN CHANG, JIUN-LING WANG, JOU-WEI LIN, LI-CHIU WU, MEI-SHU LAI, LEE-MING CHUANG, Taipei, Taiwan, Kaohsiung, Taiwan, Douliu City, Taiwan DISHA MEHTA, MARIA-ZUNILDA NÚÑEZ, ANDREW GALICA, AMIR ABDULJALIL, BRAD MANOR, MEDHA MUNSHI, PETER NOVAK, SARA MONTI, VERA NOVAK, Boston, MA, Santiago, Dominican Republic, Columbus, OH The relative contribution of individual site of infections leading to hospitalization among diabetic patients remained unclear. A retrospective study using the Taiwan National Health Insurance claims database was conducted to identify all hospitalizations related to infections in 20052007. Infections were categorized into specific sites. The incidence, fatality, hospital cost, and length of stay of overall and individual site of infections were calculated. Standardized ratio was estimated to compare the risk among diabetic with non-diabetic patients. Diabetic men and women had approximately 2-fold increased risk of overall infection as compared with non-diabetics. For diabetic men, the Microalbuminuria is a marker of renal microvascular disease that is associated with global brain atrophy and neurovascular changes in type 2 diabetes mellitus (T2DM). These changes in brain structure and function increase the risk of cognitive decline and dementia in this population. In this study, we aimed to determine the regional effects of microalbuminuria on brain tissue volume in older adults with and without T2DM. We performed a secondary analysis of data from 255 men and women aged 65±7yrs, which included 112 T2DM participants with DM duration (11.48±9.39yrs), HbA1c & For author disclosure information, see page 829. A396 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—DIABETES COMPLICATIONS 1521-P 1523-P Relationship between Diabetic Neuropathy and Sleep Apnea Syndrome—A Meta-Analysis Diabetic Kidney Disease (DKD) in UK Patients With Type 2 Diabetes (T2D) KAZUYA FUJIHARA, SATORU KODAMA, CHIKA HORIKAWA, AYUMI SUGAWARA, YORIKO HEIANZA, HITOSHI SHIMANO, YOKO YACHI, KAZUMI SAITO, OSAMU HANYU, HIROHITO SONE, Mito, Japan, Tsukuba, Japan, Niigata, Japan JAVIER CID RUZAFA, ROSIRENE PACZKOWSKI, KRISTINA S. BOYE, GIAN LUCA DI TANNA, MATTHEW J. SHEETZ, ROBERT DONALDSON, MATTHEW D. BREYER, DAVID NEASHAM, JAMES R. VOELKER, London, United Kingdom, Indianapolis, IN A high prevalence of sleep apnea syndrome (SAS) has been reported in patients with diabetes. However, it is not conclusive whether diabetic neuropathy (DN) is one of the causes of that high prevalence. Our aim of this study is to compare the prevalence of SAS between diabetic patients with and without DN. Systematic literature searches were conducted for cross-sectional studies that reported the number of patients with DN and SAS using MEDLINE and EMBASE. Odd ratios (ORs) for SAS related to DN were pooled with the Mantel-Haenszel method. Eleven eligible studies were included in this meta-analysis. The Figure shows a forest plot of ORs with 95% confidence intervals (CIs) for SAS in patients with DN compared with those not having DN. Overall, the pooled OR (95% CI) for SAS was 2.03 (1.203.43). A higher OR was observed in younger patients (mean age, ≤55 ) than in those >55 y (OR, 16.0 [95% CI, 4.07-62.9] vs. 1.50 [95% CI, 0.93-2.44]; P for interaction, 0.01). This current meta-analysis showed that a higher prevalence of SAS was observed particularly in young diabetic patients with neuropathy compared with those without neuropathy, suggesting that DN is a main contributor to SAS and that the effect of aging is small in diabetic patients. Further research is needed to elucidate the mechanisms by which DN leads to the development of SAS. Diabetes is a major cause of chronic kidney disease (CKD). We evaluated patients with T2D and presumed DKD using the Clinical Practice Research Datalink and classified them based on estimated glomerular filtration rate (eGFR) and albuminuria stages. We describe demographic factors for the prevalent patients as of 1 Oct 2006 (Table 1) and report the number of patients at each eGFR and albuminuria stage (Table 2). Presumed DKD was identified by Read codes indicating T2D plus CKD Read codes or >3 months of albuminuria or eGFR<60mL/min/1.73m2, except CKD from other etiology. We identified 111,030 prevalent patients with T2D, of whom 37% had presumed DKD, and 19,594 incident DKD patients with T2D through 31 Dec 2011. A substantial proportion of patients with T2D have DKD. The proportions with albuminuria data, on angiotensin converting enzyme inhibitors or angiotensin receptor blockers were low, suggesting a gap between clinical practice and medical evidence during the study period. Table 1. Baseline characteristics of UK patients with T2D prevalent DKD (n=41,273) eGFR 1 eGFR 2 eGFR eGFR eGFR 4 eGFR 5 eGFR 3a 3b Missing N 935 7113 21331 9364 2264 232 34 Age (years) Mean 51 65 69 75 78 74 68 Gender (%) Male 41.9 48.2 63.1 66.5 67.8 69.0 50.0 Ethnicity (from HES) (%) 86 92 94 95 95 89 75 White Blood pressure (%) 52.2 53.2 52.3 52.3 54.1 41.8 38.2 Below 140/85 HbA1c (%) >6.5% 73.2 68.8 65.6 64.5 65.3 52.6 17.6 ACE inhibitors, 70.5 66.2 63.2 70.9 68.6 49.6 41.2 ARB, or both (%) Table 2. Baseline albuminuria quantitative test results and eGFR stages, pats with T2D prevalent DKD Quantitative Quantitative Quantitative Quantitative normoalbuminuria, microalbuminuria, macroalbuminuria, albuminuria missing, n (%) n (%) n (%) n (%) eGFR 1 136 (14.5%) 206 (22.0%) 20 (2.1%) 573 (61.3%) eGFR 2 1404 (19.7%) 694 (9.8%) 40 (0.6%) 4975 (69.9%) eGFR 3a 4380 (20.5%) 501 (2.3%) 45 (0.2%) 16405 (76.9%) eGFR 3b 1662 (17.7%) 399 (4.3%) 32 (0.3%) 7271 (77.6%) eGFR 4 303 (13.4%) 141 (6.2%) 35 (1.5%) 1785 (78.8%) eGFR 5 12 (5.2%) 11 (4.7%) 9 (3.9%) 200 (86.2%) eGFR Missing 0 (0.0%) 1 (2.9%) 0 (0.0%) 33 (97.1%) 1522-P A Population-Based Prevalence Survey and Risk Factor Analysis of Diabetic Retinopathy in Beijing Changping District MING-XIA YUAN, ZHONG XIN, JIN-KUI YANG, Beijing, China This study describes the prevalence and risk factors of DR in a Chinese population in Beijing Changping district. In a total of 8,155 Chinese between 18-79 years of age, who participated in the 2010 Health Examination Survey ADA-Funded Research & Supported by: Eli Lilly and Company For author disclosure information, see page 829. Guided Audio Tour poster A397 POSTERS Supported by: NIH/NIDDK (5R21-DK084463-02); NIH/NIA (1R01AG028076-A2) Epidemiology/ Genetics in Beijing representing a population of 1,600,000 citizens in the disgrict, 3760 subjects whose FPG ≥ 5.6mmol/L were invited to the studyand 2551 subjects completed physical examination and laboratory measurements including fasting plasma glucose (FPG), OGTT-2h plasma glucose (2hPG) and hemoglobin A1c (HbA1c). The grade of DR was assessed with two 45° color digital retinal images. Of the 2551 persons, 280 with known diabetes, 334 with newly-diagnosed diabetes and 853 with impaired glucose regulation (IGR) were identified. The prevalence of DR in diabetes and IGR subjects was 9.9% and 1.2%, respectively. The prevalence of retinopathy was much lower in newly-diagnosed diabetes (2.7%) than in known diabetic subjects (18.6%). In diabetic patients, independent risk factors for retinopathy were longer diabetes duration [odds ratio (OR) 1.49 (95% CI 1.38, 1.62), for every one year increase], FPG [OR 1.32 (95% CI 1.22, 1.43), per mmol/L], 2hPG [OR 1.18 (95% CI 1.12, 1.24), per mmol/L], HbA1c [OR 1.66 (95% CI 1.45, 1.90), per 1%], and higher systolic blood pressure [OR 1.16 (95% CI 1.02, 1.31), per 10 mmHg]. The results suggest that the prevalence of DR in patients with diabetes and pre-diabetes was much lower in this study than that reported in Western countries. The major risk factors for retinopathy are longer duration of diabetes, hyperglycemia, and hypertension. (7.17±1.20 ), and 143 controls. 3D magnetization prepared rapid acquisition with gradient echo (MPRAGE) MRIs were acquired to quantify regional gray matter (GM) and white matter (WM) volumes. Least square models were used to analyze the relationship between urine albumin creatinine ratio and brain volumes adjusted for age, gender, hypertension years and glucose levels. T2DM patients had borderline higher microalbuminuria levels as compared to controls (p=0.06). In the T2DM group, microalbuminuria was associated with GM atrophy of the middle temporal gyrus (Left(L)-p=0.002; Right(R)-p=0.004), insular cortex (L-p=0.01) and supramarginal gyrus (Lp=0.01). The atrophy in WM was predominantly of the frontal lobe region of the superior frontal gyrus (L, R-p=0.02), inferior frontal lobe (L-p=0.014) and hippocampus (p=0.032). No significant relationships were observed in controls. Our cross-sectional results indicate that in T2DM patients, microalbuminuria is associated with tissue atrophy within numerous brain regions associated with cognitive function, independently of glucose and HbA1c levels. Prospective studies are thus needed to determine if microalbuminuria underlies brain atrophy and cognitive decline within this vulnerable population. EPIDEMIOLOGY—NUTRITION 1524-P Outcome Beta (SE)1 Pr > |t| Log[Predicted Fiber Intake from ME model (g)] Log[IL-6 (pg/mL)] 0.01 (0.35) 0.96 Log[CRP (mg/dL)] -0.13 (0.32) 0.67 Log[Fibrinogen (mg/dL)] -0.01 (0.05) 0.82 PWV (m/sec)2,3 -0.50 (0.47) 0.29 AIx (%)3,4 6.42 (7.46) 0.35 BrachD (% change/mmHg)3 0.77 (0.74) 0.31 1From multivariable linear regression models adjusted for predicted total energy intake from the ME model, age, gender, race/ethnicity, diabetes duration, smoking, and physical activity. Standard errors estimated using bootstrapping. 2Carotid-femoral. 3Additionally adjusted for time between assessment of diet (baseline SEARCH visit) and arterial stiffness (ancillary study visit). 4Normalized to heart rate of 75 beats/min. Protection from Fracture Risk in Long Term Type 1 Diabetes: 50-Year Medalist Study POSTERS Epidemiology/ Genetics HILLARY KEENAN, SARA TUREK, STEPHANIE HASTINGS, GEORGE L. KING, Boston, MA Individuals with type 1 diabetes (T1D) have demonstrates a 12-fold increased risk of fragility fractures over their age-matched peers. As hospitalization for fracture is highly associated with decreased quality of life, morbidity and and mortality this is an important, yet little studied diabetic complication particularly amongst those with extreme duration T1D. The 50-Year Medalist Study has extensively characterized over 800 individuals with a mean age of 69 y and duration of 55 y of T1D. Early examination of self-reported rates of hip, vertebral, and wrist fractures show extraordinarily low rates (0.33%, 0%, and 1.7%, respectively) in stark contrast to the 12-fold increase expected. To further examine these findings, 55 participants received DXA scans, 29 females, 26 males with a mean ±SD HbA1c of 7.2±0.8% and 7.0±1.2%, age 62.1±6.5 y and 66.7±6.8 y, and duration of 52.9±2.7 y and 55.8±5.1 y, respectively. BMI for this age group was low with 25.0±5.2 kg/m^2 for females and 27.3±4.4 kg/m^2 for males. T-scores, indicative of risk for fracture, for female 1/3 radius (1/3R) was -1.1±1.3, lumbar spine (LS) 0.1±1.2 and for the femoral neck (FN) -1.3±0.8. For males the 1/3R, T-score was -1.1±1.3, the LS was -0.1±1.9, and at the FN -1.3±0.8, none in the osteoporotic range. Total vitamin D, D2, D3 and calcium did not correlate with T scores among female or male, except for D3 among male and the LS T-score (R=0.5, p=0.03). There was no association of T scores with HbA1c, BMI, age or duration in either gender, p>0.05. As BMIs were low in male and female, the lower than expected risk T scores are likely not due to increase weight bearing as seen in T2D patients. These pilot data demonstrate protection from fracture, and low risk in this group with long term T1DM suggestive of a protective factor preventing bone health deterioration. & SHIRO TANAKA, YUKIO YOSHIMURA, CHIEMI KAMADA, SACHIKO TANAKA, CHIKA HORIKAWA, RYOTA OKUMURA, HIDEKI ITO, YASUO OHASHI, YASUO AKANUMA, NOBUHIRO YAMADA, HIROHITO SONE, Kyoto, Japan, Tokushima, Japan, Ibaraki, Japan, Tokyo, Japan, Mito, Japan, Niigata, Japan Foods rich in fibre, such as vegetables and fruits, prevent cardiovascular disease among healthy adults, but such data in patients with diabetes are sparse. We investigated this association in a cohort with type 2 diabetes aged 40–70 years whose HbA1C values were ≥6.5%. After excluding nonresponders to a dietary survey, 1414 patients were analysed. Baseline dietary intake was assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to coronary heart disease (CHD) and stroke. Mean daily dietary fibre in quartiles ranged from 8.7 to 21.8 g and mean energy intake ranged from 1442.3 to 2058.9 kcal. Mean daily intake of vegetables and fruits in quartiles ranged from 228.7 to 721.4 g. During the 8-year follow-up, incidents according to quartiles of dietary fibre were 22, 15, 13, and 18 for stroke and 21, 24, 27, and 24 for CHD. Table 1 shows the results of Quartile Cox regression, showing inverse associations. There were no significant associations with CHD. The HR per 1 g increase was smaller for soluble dietary fibre (0.48, 0.30–0.79, p<0.01) than for total (0.82, 0.73–0.93, p<0.01) and insoluble dietary fibre (0.79, 0.68–0.93, p<0.01). The incidence rate of stroke was estimated to be lower than 0.90 per 1000 patient-years among patients consuming over 25 g daily of dietary fibre. In conclusion, increased dietary fibre, particularly soluble fibre, and vegetables and fruits reduce incident stroke but not CHD. EPIDEMIOLOGY—NUTRITION Guided Audio Tour: Nutritional Epidemiology in Diabetes (Posters: 1525-P to 1531-P), see page 17. & 1526-P Intakes of Dietary Fiber, Vegetables, and Fruits and Incidence of Cardiovascular Disease in Japanese Patients With Type 2 Diabetes 1525-P Association of Dietary Fiber Intake With Inflammation and Arterial Stiffness in Youth With Type 1 Diabetes LINDSAY M. JAACKS, JAMIE L. CRANDELL, ANGELA D. LIESE, ARCHANA P. LAMICHHANE, RONNY A. BELL, DANA DABELEA, RALPH B. D’AGOSTINO, JR., LAWRENCE M. DOLAN, SANTICA M. MARCOVINA, KRISTI REYNOLDS, AMY S. SHAH, ELAINE M. URBINA, PAUL WADWA, ELIZABETH J. MAYER-DAVIS, Chapel Hill, NC, Columbia, SC, Winston-Salem, NC, Denver, CO, Cincinnati, OH, Seattle, WA, Pasadena, CA Table 1. Cox regression analysis of incidence of stroke and intake of total, soluble and insoluble dietary fibre and vegetables and fruits Q2 v.s. Q1 Q3 v.s. Q1 Q4 v.s. Q1 HR 95%CI p HR 95%CI p HR 95%CI p Total dietary fibre 0.44 (0.20–0.95) 0.04 0.37 (0.15–0.91) 0.03 0.39 (0.12–1.29) 0.12 Soluble dietary fibre 0.45 (0.21–0.96) 0.04 0.37 (0.15–0.89) 0.03 0.32 (0.10–1.02) 0.05 Insoluble dietary fibre 0.55 (0.26–1.16) 0.11 0.36 (0.15–0.89) 0.03 0.44 (0.14–1.40) 0.16 A high-fiber diet may be protective against the development of atherosclerosis and subsequent vascular disease. We characterized the association of fiber intake with inflammation and arterial stiffness using cross-sectional data from youth ≥ 10 years old with clinically diagnosed type 1 diabetes (T1D) for ≥ 3 months and ≥ 1 positive autoantibody in the SEARCH for Diabetes in Youth Study. Dietary fiber and energy intake were assessed by food frequency questionnaire with measurement error (ME) accounted for by a structural sub-model derived using additional 24-hour dietary recall data in a calibration sample. Markers of inflammation included IL-6 and CRP (n=1308) and fibrinogen (n=1244); markers of arterial stiffness available in a subset of participants included pulse wave velocity (PWV; n=183), augmentation index (AIx; n=179) and brachial distensibility (BrachD; n=176). Mean (SD) diabetes duration was 51.1 (43.5) months; 12.5% of participants were obese. Mean (SD) predicted fiber and energy intake from the ME model were 14.6 (2.8) g/ day and 2064 (380) kcal/day, respectively. Fiber intake was not significantly associated with inflammation or arterial stiffness (Table). In conclusion, among youth with T1D of relatively short duration, fiber intake is not associated with measures of systemic inflammation or vascular stiffness. Whether fiber intake is associated with these outcomes in patients with T1D of greater duration requires further study. Vegetables and fruits 0.72 (0.36–1.44) 0.35 0.45 (0.19–1.04) 0.06 0.35 (0.13–0.96) 0.04 HR: hazard ratio, CI: confidence interval *Adjusted for age, sex, body mass index, HbA1C, diabetes duration, diabetic retinopathy, treatment by insulin, treatment by oral hypoglycaemic agents, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, current smoker, physical activity, alcohol intake, proportions of total fat, saturated fatty acids, n-6 fatty acids and n-6 fatty acids, dietary cholesterol and sodium intake and total energy intake. Supported by: Ministry of Health, Labour and Welfare (Japan) & For author disclosure information, see page 829. A398 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—NUTRITION hyperandrogenism in lean women with PCOS. Sixty lean women with PCOS were randomized to one of two 1800 kcal isocaloric diets with different meal timing: 1) High Calorie Breakfast Diet (BREdiet): 700 Kcal breakfast with %carbohydrate;protein;fat: 50:30:20%; lunch (600 Kcal,20:45: 25 %), and small dinner (200 Kcal, 13:40:47 %). 2) High Calorie Dinner Diet (DINdiet: 200 Kcal breakfast 13:40:47 %), lunch (600 Kcal,20:45:25 %), and large dinner (700 Kcal,50:30: 20 %). Ovarian P450c17 alpha activity, fasting serum steroids, and insulin resistance by oral glucose tolerance were assessed. Subjects were 29.4 ± 6.5 yrs of age with BMI 23.0 ± 0.64 kg/m2. No change in BMI occurred over 90 days. Area under the curve (AUC) glucose and AUC insulin did not change in the DINdiet. In the BREdiet group, AUC glucose and insulin decreased significantly; basal serum 17 alpha-hydroxyprogesterone decreased from 128 ± 21 to 66 ± 18 ng/dL (P = 0.05); serum sex hormonebinding globulin (SHBG) increased from 2.5 ± 0.4 to 4.9 ± 0.8 µg/dL (P = 0.003). Isocaloric diets with different meal timing influence glucose metabolism and free testosterone plasma levels in women with PCOS. The BREdiet may facilitate the therapeutic management of women with PCOS. 1527-P White Rice Consumption and Incident Risk for Type 2 Diabetes Mellitus in Japanese Men and Women MASARU SAKURAI, KOSHI NAKAMURA, KATSUYUKI MIURA, TOSHINARI TAKAMURA, KATSUSHI YOSHITA, SHIN-YA NAGASAWA, YUKO MORIKAWA, MASAO ISHIZAKI, TERUHIKO KIDO, YUCHI NARUSE, HIDEAKI NAKAGAWA, Uchinada, Japan, Otsu, Japan, Kanazawa, Japan, Osaka, Japan, Toyama, Japan We have reported the association between dietary glycemic index (GI) and the incidence of diabetes in Japanese men (Metabolism, 2012). Rice, especially white rice, is the major contributor to dietary GI for Japanese. However, there are only a few studies which have evaluated the association between white rice intake and the incidence of diabetes from Japan. We examined the relationship between white rice intake and 7-year incidence risk of diabetes in Japanese men and women. Participants were 3,515 employees (2,035 men and 1,480 women) of a metal products factory in Japan. We measured consumption of white rice using a self-administered diet history questionnaire. The incidence of diabetes was determined in annual medical examination over a 7-year period. Hazard ratios (HRs) with 95% confidence intervals for diabetes were estimated, with adjustment for age, sex, body mass index (BMI), family history of diabetes, dietary and other lifestyle factors. The mean participant age at baseline was 46.2 years and the mean BMI was 23.0 kg/m2. Mean (SD) consumption of white rice was 183 (86) g/1,000 kcal. During the study, 273 participants developed diabetes (12.2 / 1,000 person-years). Adjusted HRs (95% confidence interval) for diabetes across the quartile of white rice consumption were 1.00 (reference), 1.26 (0.87-1.83), 1.36 (0.95-1.96), and 1.40 (0.96-2.04), and significant linear association was observed between white rice consumption and incidence of diabetes (P for trend = 0.016). No interaction was observed between sex and rice consumption with regard to the association with incidence of diabetes. White rice consumption was significantly associated with the risk for diabetes in Japanese men and women. MOLLY M. LAMB, MILISSA MILLER, MIRANDA KROEHL, MARIAN J. REWERS, JILL M. NORRIS, Aurora, CO, Toronto, ON, Canada Dairy exposure has been inconsistently associated with IA and Type 1 Diabetes (T1D) development. We examined interactions between dairy introduction in infancy, childhood dairy consumption, and HLA genotype in IA development. DAISY has followed children at increased T1D risk for IA development (presence of autoantibodies to insulin, GAD65 or IA-2 twice in succession) and T1D development. We examined 1,828 DAISY children with available dietary data, 135 of whom developed IA, and 36 of whom subsequently developed T1D. Childhood diet was collected prospectively via parent- and self-reported food frequency questionnaires (FFQ). HLA genotype was defined as high risk: HLA-DR3/4,DQB1*0302; and low/moderate risk: all other genotypes. In a survival model adjusted for total calories, FFQ type, family history of T1D, and ethnicity, childhood lactose consumption was associated with IA development. Children with low/moderate risk HLA genotypes (n = 1414) had an increased risk for IA development (Hazard Ratio: 1.32, 95% Confidence Interval: 1.04-1.68). In children with high risk HLA genotype (n = 414), childhood lactose consumption was associated with decreased IA risk for those introduced to dairy later in infancy (Figure). Similar results were seen for childhood dairy protein consumption. Childhood dairy consumption may modify the effect of HLA genes and infant dairy exposure on IA development. 1528-P High-Calorie Breakfast Improves Weight Loss and Metabolism vs. Isocaloric Meal at Dinner in Obese Women With Metabolic Syndrome DANIELA JAKUBOWICZ, JULIO WAINSTEIN, OREN FROY, Holon, Israel, Rehovot, Israel The effect of meal timing on weight loss and metabolic syndrome is unknown. The present study was designed to compare two isocaloric weight loss diets with calorie loading at breakfast vs. dinner. Subjects included 93 obese women (BMI 32.4 ± 1.8 kg/m2) with metabolic syndrome who were randomized into two isocaloric (~1400 kcal) weight loss diets, a breakfast (BF) diet (700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) or a dinner (D) diet (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner) for 12 weeks. Anthropometric measurements, oral glucose tolerance test (OGTT) and meal tests were performed. After 12 weeks, the BF group showed greater weight loss (-8.7±1.4 vs. -3.6±1.5 kg) and reduction in waist circumference (-8.5±1.9 vs. -3.9±1.4 cm) compared with the D group. Although fasting glucose, insulin, ghrelin levels as well as HOMA-IR, and HOME-B were reduced in both groups, fasting glucose, insulin and HOMA-IR decreased significantly to a greater extent in the BF group. In addition, mean triglyceride levels decreased by 33.6% in the BF group, but increased by 14.6% in the D group. Total cholesterol slightly decreased only in the BF group. After OGTT, the extent of reduction of AUCglucose and AUCinsulin was significantly greater in the BF (-22% and -58%, respectively) compared with the D group. In response to a meal challenge, the overall daily AUCglucose AUCinsulin, AUCghrelin and mean hunger scores were significantly lower, whereas mean satiety scores were significantly higher in the BF group. An Isocaloric diet with switched caloric intake during breakfast and dinner differentially influences weight loss, waist circumference, appetite and ghrelin and lipid levels. High-calorie breakfast with reduced intake at dinner might be a useful alternative for the management of obesity and metabolic syndrome. & 1530-P & 1529-P 1531-P The Influence of Meal Timing on Glucose Metabolism and Hyperandrogenism in Lean Women With Polycystic Ovary Syndrome Association between Detetary Sodium Intake and Cardiovascular Complications in a French Cohort of Type 2 Diabetes Patients DANIELA JAKUBOWICZ, YOSEFA BAR DAYAN, JULIO WAINSTEIN, Holon, Israel PIERRE-JEAN SAULNIER, RONAN ROUSSEL, RICHARD MARECHAUD, PHILIPPE SOSNER, STEPHANIE RAGOT, SAMY HADJADJ, Poitiers, France, Paris, France Weight loss improves insulin resistance and hyperandrogenism in obese women with PCOS but is unnecessary in lean women with PCOS; however, meal timing and composition may influence glucose metabolism and hyperandrogenism. The study was designed to investigate the effects of two isocaloric diets with different meal timing on insulin resistance and ADA-Funded Research & In type 1 diabetes and in the general population, epidemiological data suggest that sodium intake is associated with cardiovascular outcomes with a J-shape curve. However no data examined the association of sodium intake and cardiovascular or renal complications in type 2 diabetes patients. For author disclosure information, see page 829. Guided Audio Tour poster A399 POSTERS & & Dairy Introduction in Infancy, Childhood Dairy Consumption and HLA Interact to Affect Risk of Islet Autoimmunity (IA): The Diabetes Autoimmunity Study in the Young (DAISY) Epidemiology/ Genetics & EPIDEMIOLOGY—NUTRITION We performed an observational evaluation in an inception cohort of 1486 type 2 diabetes patients. Baseline daily urinary sodium excretion (UNa) was calculated by Tanaka’s formula from spot urine. We used Cox proportional hazard model to estimate associations between predictors and complication outcome. Median follow-up was 56 months during which 193 cardiovascular deaths occurred. The mean value of UNa was 161±48 mmol/day. UNa was significantly and nonlinearly associated with cardiovascular mortality (p=0.0455) (Figure 1). This association persisted after adjustment on age, sex, diabetes duration, estimated glomerular filtration rate, urinary albumin excretion, prior history of myocardial infarction and systolic blood pressure. We also found a non linear J-shaped significant association between UNa and risk of cardio-renal composite outcome (cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure and end stage renal disease) after multiple adjustment (p=0.0452) In type 2 diabetes patients, a nadir of UNa approximating 180 mmol/day was associated with a least risk for severe complications. 1533-P High Caloric Intake Is Associated With Longitudinal Deterioration of Insulin Sensitivity and Beta-Cell Function in Women after Gestational Diabetes Mellitus Short-term dietary restriction can improve insulin sensitivity and beta-cell function. Few studied the impact of chronic dietary intake. We examined the relationship between dietary intake under free-living conditions and the longitudinal trajectory of metabolic traits. Subjects were 62 Hispanic women with gestational diabetes mellitus (GDM) without T2D at 15-month postpartum who underwent follow-up every 12-15 months for up to 12 years postpartum. Self-reported food frequency and physical activity (PA) questionnaires, bioelectrical impedance to assess percent body fat (%BF), oral (oGTT) and intravenous (ivGTT) glucose tolerance tests were performed at baseline and every follow-up visit. Mixed effects models were used for data analyses. Subjects characteristics at baseline were (mean±SD) age: 32±6 years, BMI: 30.4±4.9 kg/m2, total caloric intake: 2111±1116 kcal/day. 68% of the cohort reported zero mins/wk of moderate and vigorous activities. Dietary intake did not change significantly during follow-up (p>0.24). After adjustment for baseline age, BMI, PA, baseline values of each outcome, and change in BMI, high baseline caloric intake was significantly associated with greater decline of insulin sensitivity (SI) and beta-cell function (DI) over time (p=0.012 and 0.0003, respectively). The adjusted mean rates of change were -0.14 vs. -0.02 units/yr for SI, and -371.4 vs. -155.6 units/yr for DI comparing women with baseline caloric intake above vs. below the cohort median. Analysis of macronutrients indicated that baseline fat density was positively associated with rates of change in BMI (p=0.005) and %BF (p=0.04). High fat density was significantly associated with faster increase of fasting glucose (FSG; p=0.033) adjusted for baseline FSG and change in BMI. Our findings indicate that a diet rich in calories and fat accelerates the deterioration of insulin sensitivity and beta-cell function in women after GDM. POSTERS Epidemiology/ Genetics ZANGHUA CHEN, RICHARD M. WATANABE, DANIEL O. STRAM, THOMAS A. BUCHANAN, ANNY H. XIANG, Los Angeles, CA, Pasadena, CA Supported by: PHRC interrégional; AFD Recherche (2003); ALFEDIAM (2009); GEM 1534-P Role of G308A Variant of Tumor Necrosis Factor Alpha Gene on Weight Loss and Insulin Resistance after Two Diets 1532-P DANIEL DE LUIS, ROCIO ALLER, OLATZ IZAOLA, ENRIQUE ROMERO, Simancas, Spain WITHDRAWN The aim of our study was to investigate the influence of G-308A promoter variant of the TNF alpha gene on metabolic changes and weight loss secondary to a high monounsaturated fat vs a high polyunsaturated fat hypocaloric diets in obese subjects. A sample of 261 obese subjects was enrolled in a prospective way. In the basal visit, patients were randomly allocated during 3 months to; Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). One hundred and ninety seven patients (73.2%) had the genotype G-308G and 64 (26.8%) patients had the genotype G-308A. There were no significant differences between the effects (on weight, BMI, waist circumference, fat mass) in either genotype group with both diets. With the diet type P and in genotype G-308G, glucose levels (-6.7+22.1 mg/dl vs -3.7+2.2 mg/dl:p<0.05), HOMA-R (-0.6+2.1 units vs -0.26+3.1 units:p<0.05), insulin levels (-1.7+6.6 UI/L vs -0.6+7.1 UI/L:p<0.05), total cholesterol levels (-15.3+31.1 mg/dl vs -8.4+22.1 & For author disclosure information, see page 829. A400 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—NUTRITION mg/dl:p<0.05), LDL cholesterol levels (-10.7+28.1 mg/dl vs -3.8+21.1 mg/ dl:p<0.05) and triglycerides (-12.1+52.1 mg/dl vs -6.6+43.1 mg/dl:p<0.05) decreased. In conclusion, carriers of G-308G promoter variant of TNFalpha gene have a better metabolic response than A-308 obese with a high polyunsaturated fat hypocaloric diet. 1537-P Macronutrient Composition in Weight Loss Diets: A Meta-Analysis MONA BOAZ, DANIELA JAKUBOWICZ, JULIO WAINSTEIN, Holon, Israel Despite their poor long term performance, dietary interventions for weight loss remain the first line treatment for obesity. This meta-analysis was designed to compare low fat to low carbohydrate diets in terms of weight loss or maintenance of weight loss. Studies were included in this meta-analysis if they were 1) well-designed randomized clinical trials comparing low fat to low carbohydrate diets; 2) included healthy overweight and obese adults; 3) measured body weight as the primary endpoint; 4) were published in 2009 or later. Four studies meeting all inclusion criteria were identified. Together, these studies included 1878 subjects, 941 of whom were exposed to low carbohydrate diets and 937 to low fat diets. Two of the studies targeted weight loss as the primary endpoint, and two focused on maintenance of weight lost using meal replacement products. Overall compliance was poor and attrition was high across studies. In a random effects model, no significant advantage to either diet strategy could be identified - standardized differnece in means -0.07, 95% CI -0.3-0.4, p=0.7. Manipulation of macronutrient composition of weight loss diets does not appear to be associated with significantly different weight loss outcomes. Both types of macronutrient-centered weight loss diets appear to be associated with poor adherence and high attrition rates. Novel weight loss strategies must be investigated. 1535-P Association of 25(OH)D With Insulin Resistance and Beta Cell Function in an Aboriginal Canadian Community SHEENA KAYANIYIL, ALAA BADAWI, STEWART B. HARRIS, BERNARD ZINMAN, ANTHONY J. HANLEY, Toronto, ON, Canada, London, ON, Canada Aboriginal Canadian populations living in northern environments are at increased risk of both type 2 diabetes (T2DM) and vitamin D deficiency. Emerging evidence suggests a role for low vitamin D in the etiology of T2DM, but data examining this association in Aboriginal groups in Canada are limited. Our objective was to determine the cross-sectional association of vitamin D [25-hydroxyvitamin D, 25(OH)D] with risk of T2DM and related traits, specifically insulin resistance (IR) and beta (β)-cell dysfunction in 445 Aboriginal Canadian participants in a community-wide survey in 2003-05. Participants’ mean age and BMI were 34y and 29.8 kg/m2, respectively, and 59% were female. Serum 25(OH)D was measured using a competitive chemiluminescence immunoassay. Fasting blood samples were collected, and 75g oral glucose tolerance tests (OGTT) were administered. Insulin sensitivity was measured using the Matsuda index (ISOGTT) and HOMA-IR. β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the Insulin Secretion Sensitivity Index-2 (ISSI-2). Multivariate regression models adjusted for age, sex, season, PTH, vitamin D supplement use, and % body fat. The mean 25(OH)D concentration was 23.2 ± 9.6 nmol/L; 98.4% had insufficient 25(OH)D levels (<50 nmol/L). Linear regression analyses indicated significant associations of 25(OH)D with both ISOGTT and HOMA-IR [β=0.015 (95% CI 0.007, 0.002) and β=-0.013 (-0.02, -0.004), respectively], as well as with both IGI/IR and ISSI-2 [β=0.017 (0.002, 0.03) and β=0.011 (0.004, 0.02), respectively]. Logistic regression analyses indicated a significantly reduced risk of OGTT-detected T2DM [OR=0.45 (0.22, 0.91)] per SD increase in 25(OH)D. In conclusion, low 25(OH)D levels were significantly associated with poor insulin sensitivity and β-cell function, as well as an increased risk of type 2 diabetes in an Aboriginal Canadian population with a high prevalence of vitamin D insufficiency. 1538-P In people with diabetes, recent observational studies have found an association between low baseline 24h urinary sodium excretion (24hUNa) and the subsequent risk for increased mortality. The aim of this study was to determine whether a similar relationship exists between serial 24hUNa measurements and mortality. We studied patients with type 2 diabetes (n=638) attending a single diabetes clinic. Baseline characteristics were determined in 2001 and follow up was completed in 2010. Serial 24hUNa was measured at 6-12 month intervals. A joint model was developed comprising a longitudinal Linear Mixed Model and a Weibull Parametric Survival model to take into account the association between both the longitudinal 24hUNa and eGFR measurements and total mortality. Significant independent predictors of the longitudinal Linear Mixed Model were: time, 24hUNa as a continuous variable over the observational period, baseline eGFR, AER, age and BMI. Significant independent predictors of the survival component of the joint model were: 24h UNa over time, baseline eGFR, eGFR over the observational period, presence of CHF and/or AF, duration of diabetes, baseline HDL and diastolic blood pressure. The model showed that low 24hUNa over time was independently associated with increased mortality in type 2 diabetes (FIGURE). These data call for interventional studies to determine if dietary sodium intake has a causative role in determining adverse outcomes in patients with type 2 diabetes. Supported by: CIHR 1536-P Chewing Areca Nut and Risk of Metabolic Diseases, Cardiovascular Disease, and All-Cause Mortality: A Meta-Analysis TOMOHIDE YAMADA, KAZUO HARA, TAKASHI KADOWAKI, Tokyo, Japan Areca nut (AN) (Betel nut) is a fruit of the Areca catechu tree. Approximately 600 million individuals chew AN regularly worldwide and it is a known risk factor for oral cancer. Several studies have shown that chewing AN influences the risk of systemic diseases. We performed a meta-analysis to assess the influence of chewing AN on metabolic diseases, cardiovascular disease, and all-cause mortality. We searched Medline and the Cochrane Library for pertinent articles (including their references) published between 1951 and 2012. Only English language reports of original observational studies were included. Data were extracted independently by two reviewers. The adjusted relative risk (RR) and 95% confidence interval (95% CI) were calculated using the random effect model. Sex was used as an independent category for comparison. Of 569 potentially relevant studies, 16 studies (8 cohort studies and 8 case-control studies) covering 385,933 subjects (range: 1,049 to 97,244) conformed to the selection criteria of 21 comparison categories. All of these studies were performed in Asia. Pooled analysis showed that the adjusted RR for AN use compared with nonuse was 1.56 (95% CI: 1.2-2.03; p=0.001) for metabolic syndrome (N=5), 1.36 (95% CI: 1.05-1.76; p=0.02) for obesity (N=6), 1.47 (95% CI: 1.2-1.81; p<0.001) for diabetes (N=2), 1.45 (95% CI: 0.98-2.15; p=0.06) for hypertension (N=4), 1.2 (95% CI: 1.03-1.4;p=0.02) for cardiovascular disease (N=6), and 1.22 (95% CI: 1.03-1.44; p=0.02) for allcause mortality (N=5). The funnel plot, Begg’s test, and Egger’s test did not show any evidence of publication bias (all P≥0.05). In conclusion, chewing AN is associated with an increased risk of several metabolic diseases, as well as cardiovascular disease and all-cause mortality. Stopping AN use could be valuable in terms of preventing metabolic diseases, especially considering the rapid increase in the prevalence of such diseases in South-East Asia and the Western Pacific. ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A401 POSTERS ELIF I. EKINCI, JOHN MORAN, KAREY CHEONG, MERLIN THOMAS, SOPHIE CLARKE, AMANDA LEONG, ANGELA CHEN, MATTHEW DOBSON, RICHARD J. MACISAAC, GEORGE JERUMS, Melbourne, Australia, Adelaide, Australia Epidemiology/ Genetics Relationship between Serial 24h Urinary Sodium Excretion and Mortality in Type 2 Diabetes EPIDEMIOLOGY—OTHER EPIDEMIOLOGY—OTHER 1541-P Exploration of Efficient Case Ascertainment Methods for Surveillance of Childhood Diabetes Using Electronic Health Data: The SEARCH for Diabetes in Youth Study, Carolina Site 1539-P Dietary Glycemic Index during Pregnancy Is Associated With Biomarkers of the Metabolic Syndrome in Offspring at Age 20 Years WENZE ZHONG, EMILY R. PFAFF, JOAN THOMAS, LINDSAY M. JAACKS, TIMOTHY S. CAREY, DANIEL P. BEAVERS, SHARON H. SAYDAH, JEAN M. LAWRENCE, RICHARD F. HAMMAN, DANA DABELEA, CATHERINE PIHOKER, ELIZABETH J. MAYER-DAVIS, Chapel Hill, NC, Winston-Salem, NC, Atlanta, GA, Pasadena, CA, Aurora, CO, Seattle, WA POSTERS Epidemiology/ Genetics INGE DANIELSEN, CHARLOTTA GRANSTRÖM, THORHALLUR HALDORSSON, DORTE RYTTER, BODIL HAMMER BECH, TINE BRINK HENRIKSEN, ALLAN VAAG, SJURDUR OLSEN, Copenhagen, Denmark, Reykjavik, Iceland, Aarhus, Denmark Growing evidence indicates that MS is rooted in fetal life with a potential key role of nutrition during pregnancy. The objective of the project was to assess the possible associations between the dietary glycemic index (GI) and glycemic load (GL) during pregnancy and biomarkers of the metabolic syndrome (MS) in young adult offspring. Dietary GI and GL were assessed by questionnaires and interviews in gestation week 30 and offspring were clinically examined at the age of 20 years. Analyses based on 439 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, pre-pregnancy body mass index (BMI), education, energy intake, and the offspring’s ambient level of physical activity. In addition, possible confounding by gestational diabetes mellitus was taken into account. Main outcome measures: Waist circumference, blood pressure, HOMA insulin resistance (HOMA-IR) and plasma levels of fasting glucose, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, insulin, and leptin were measured in the offspring. Significant associations were found between dietary GI in pregnancy and HOMA-IR (the relative increase in HOMA-IR per 10 units’ GI increase was 1.08 [95% CI: 1.01, 1.16], p=0.02), insulin (1.08 [95% CI: 1.01, 1.16], p=0.02) and leptin (1.21 [95% CI: 1.07, 1.38], p=0.004) in the offspring; whereas no associations were detected for GL. Exclusion of 11 women diagnosed with gestational diabetes mellitus did not change the results. Our data suggests that high dietary GI in pregnancy may affect MS marker levels in young adult offspring in a potentially harmful direction. We used electronic health data from the University of North Carolina Health Care System’s Data Warehouse to explore approaches for efficient childhood diabetes (DM) case ascertainment. 57,767 children aged 0-19 years who were seen by a health care provider for any reason in 2011 were identified. From these, 1348 presumed DM cases were selected who met ≥ 1 of the following criteria using data back to July 1st 2008: 1) HbA1c ≥ 6.0%; 2) ≥ 1 fasting glucose ≥ 126mg/dl or ≥ 2 random glucose ≥ 200mg/ dl on different days; 3) ≥ 1 DM-related ICD-9 codes on problem list ; 4) ≥ 1 DM-related ICD-9 billing codes; 5) any DM medications. Children who didn’t meet any of the listed criteria were assumed non-diabetic. Medical record review of 1348 presumed cases yielded 537 true DM cases. Among the criteria, billing codes had the best performance with a high sensitivity (97.0%) and a moderate positive predictive value (PPV) (82.2%) (Table). Although by design, meeting ≥1 criteria had a sensitivity of 100%, the PPV was low (39.8%). When ≥ 2 criteria were met, the PPV improved to 77.2%, but the sensitivity decreased to 91.6%. When ≥3 or ≥4 or 5 criteria were met, sensitivity dropped greatly (81.8% -37.6%). While further analyses will consider combinations of number and type of criteria by DM type, use of billing data may provide the most efficient approach to initial surveillance, with little gain from use of more complex data sources. Table. Validation of single and multiple criteria in identifying childhood diabetes cases in the University of North Carolina Health Care System’s Data Warehouse (source population n=57,767; total presumed cases n=1348; true cases n=537) Supported by: Danish Council for Strategic Research criteria met False Sensitivity Specificity Positive Negative positive n (%) (%) predictive predictive (%) value (%) value (%) HbA1c 486 99(20.4) 72.1 99.8 79.6 99.7 Fasting/random glucose 857 464(54.1) 73.2 99.2 45.9 99.7 Diabetes related ICD-9 266 8(3.0) 48.0 99.9 97.0 99.5 codes* on problem list Diabetes related ICD-9 634 113(17.8) 97.0 99.8 82.2 99.9 billing codes Diabetes medications¶ 782 299(38.2) 89.9 99.5 61.8 99.9 # of criteria met At least 1 1348 811(60.2) 100.0 98.6 39.8 100.0 At least 2 637 145(22.8) 91.6 99.7 77.2 99.9 At least 3 458 19(4.1) 81.8 99.9 95.9 99.8 At least 4 378 6(1.6) 69.3 99.9 98.4 99.7 5 204 2(1.0) 37.6 99.9 99.0 99.4 *Diabetes related ICD-9 codes included: 250.xx (diabetes); 775.1 (neonatal diabetes); 648.0x (diabetes in pregnancy, non-gestational); 357.2 (diabetic retinopathy); 362.0x (diabetic retinopathy); 366.4 (diabetic cataract) ¶ Diabetes medications included: insulin, metformin, GLP-1, glucagon, sulfonylureas, Thiazolidnediones, and other hypoglycemic agents such as acarbose and nateglinide. 1540-P Is Genetic Ancestry Associated With Incident Type 2 Diabetes? REBECCA PICCOLO, JOHN B. MCKINLAY, JAMES B. MEIGS, RICHARD GRANT, LISA D. MARCEAU, Watertown, MA, Boston, MA, Oakland, CA Type 2 Diabetes (T2D) is more prevalent among Black and Hispanic minority populations in the US relative to Whites. Genetic ancestry (as measured by Ancestry Informative Markers, AIMs) is associated T2D, HbA1c and insulin resistance in recent studies. However, the association between ancestry and T2D appears to be almost totally confounded by socioeconomic factors. In order to further quantify the association between genetic ancestry, socioeconomic factors, and T2D we used data from the longitudinal Boston Area Community (BACH) Survey. The BACH Survey is a racially/ethnically diverse, longitudinal, epidemiologic study of community-dwelling residents of Boston. A panel of 63 AIMs designed to discriminate African, Native American, and European ancestry were collected from 2,732 non-diabetic participants, along with a breadth of measures including: sociodemographics, health care access/utilization, lifestyle/ behavior, health status, physical measures, and biochemical parameters. We examined the relationship between % African and % Native American ancestry on incident T2D (average follow-up = 7.2 years). In ageand gender-adjusted models, the odds of developing T2D were 14% higher (OR= 1.14, 95% CI [1.07-1.22]) for every 10% increase in African ancestry (relative to European ancestry). Results were similar for Native American ancestry although not statistically significant (OR=1.14 [ 0.97,1.33]). As in previous studies, these results were attenuated with further adjustment for socioeconomic factors (African ancestry: OR=1.07, [0.99-1.15]; Native American ancestry: OR=0.99, [0.83-1.18]). Further, genetic ancestry only accounted for 0.3% of the variation in T2D incidence (by comparison, income, education, and occupation accounted for 1.4% and BMI 1.6%). We conclude that while African and Native American genetic ancestry are associated with incidence of T2D in minimally adjusted models, the effect of genetic ancestry on T2D is likely explained by differences in socioeconomic position. n Supported by: CDC 1542-P Extent of Increase Over Time in U.S. Diabetes Prevalence Explained by Race-Ethnicity, Aging, and Obesity Trends ANDY MENKE, KEITH F. RUST, YILING J. CHENG, CATHERINE C. COWIE, Silver Spring, MD, Rockville, MD, Atlanta, GA, Bethesda, MD The prevalence of diabetes has been increasing over the past few decades. This has coincided with an increase in certain risk factors for diabetes, such as a changing race-ethnicity distribution, an aging population, and an increase in obesity prevalence. It is unclear how much the increased prevalence of diabetes is due to an increase in these known risk factors and how much is due to other factors. We used data from participants ages 20-74 years (for consistency across survey years) in the National Health and Nutrition Examination Survey (NHANES) II (1976-1980; N=4570), NHANES Supported by: NIH/NIDDK (U01DK056842), (R01DK080786) & For author disclosure information, see page 829. A402 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—OTHER III (1988-1994; N=7278), NHANES 1999-2002 (N=4118), NHANES 2003-2006 (N=3961), and NHANES 2007-2010 (N=5109), all nationally representative samples of the U.S. population. Diabetes, defined as a self-reported diagnosis or fasting plasma glucose ≥126 mg/dL (common measures for all surveys), increased among men from 4.8% in 1976-1980 to 11.3% in 2007-2010, and among women from 5.7% in 1976-1980 to 8.6% in 2007-2010 (both p-trends <0.001). Using logistic regression, adjustment for age, race-ethnicity, and body mass index decreased the diabetes slope over time by 47% among men and 110% among women. Changes over time in the distribution of age, race-ethnicity, and body mass index explains about half of the increase in diabetes prevalence in men and the entire increase in diabetes prevalence in women in the U.S. population between 1976-1980 and 2007-2010. 1544-P Depressive Symptoms and Incidence of Diabetes Percent of diabetes slope over time explained by differences in the distribution of race-ethnicity, age, and body mass index Logit (SE) of diabetes Percent explained per 1 year increase by covariate Men Unadjusted 0.0310 (0.0035) — Age 0.0311 (0.0037) -0.3 Race-ethnicity 0.0306 (0.0036) 1.3 Body mass index, kg/m2 0.0184 (0.0038) 40.6 All 3 combined 0.0163 (0.0042) 47.4 Residual — 52.6 Women Unadjusted 0.0154 (0.0034) Age 0.0140 (0.0036) 9.1 Race-ethnicity 0.0138 (0.0035) 10.4 Body mass index, kg/m2 -0.0011 (0.0035) 107.1* All 3 combined -0.0015 (0.0039) 109.7* Residual — — *Values >100% indicate a decrease in diabetes prevalence over time after adjustment 1545-P Supported by: NIDDK (GS10F0381L) Sex Steroid and Sex Hormone Binding Globulin Changes in Premenopausal Women in the Diabetes Prevention Program (DPP) 1543-P CATHERINE KIM, F. XAVIER PI-SUNYER, ELIZABETH L. BARRETT-CONNOR, FRANKIE B. STENTZ, MARY BETH MURPHY, SHENGCHUN KONG, BIN NAN, ABBAS E. KITABCHI, FOR THE DIABETES PREVENTION PROGRAM, Ann Arbor, MI, New York, NY, San Diego, CA, Memphis, TN Paternal Diabetes Is Associated With Lower Birth Weight in the UK Biobank Study of 500,000 Individuals JESSICA S. TYRRELL, HANIEH YAGHOOTKAR, RACHEL M. FREATHY, ANDREW T. HATTERSLEY, TIMOTHY M. FRAYLING, Truro, United Kingdom, Exeter, United Kingdom Our objective was to examine associations between intensive lifestyle modification (ILS) and metformin and changes in SHBG and sex steroids (estradiol, testosterone, dehydroepiandrosterone, androstenedione [A4]) in premenopausal women. The DPP was a randomized trial designed to assess the impact of ILS and metformin upon diabetes incidence in overweight, glucose-intolerant adults. We examined a subgroup of participants who were premenopausal women; non-Hispanic white (NHW), African-American (AA), or Hispanic (H) race/ ethnicity; and who did not use estrogen (n=301). Main outcome measures were changes in sex hormones between baseline and 1-year by study arm and race/ethnicity. ILS, but not metformin, increased median SHBG by 3.1 nmol/l (about 11%) compared to decreases of 1.1 nmol/l in the placebo arm (p<0.05), with differences persisting after adjustment for age, race/ethnicity, and changes in waist circumference. Neither intervention changed any sex steroids compared to placebo. SHBG changes were not associated with fasting glucose or post-challenge glucose changes. Racial/ethnic comparisons were not significant. The exception was that median baseline A4 was lower in Hs compared to NHWs (5.7 nmol/l vs. 6.5 nmol/l, p<0.05), and median increases in A4 were also greater in Hs compared to NHWs (3.0 nmol/ vs. 1.2 nmol/l, p<0.05). These differences persisted after adjustment for waist circumference. Among premenopausal glucose intolerant women, ILS increased SHBG, but this was not associated with reductions in fasting or 2-hour glucose. Sex steroids were similar by race/ethnicity, with the possible exception of lower A4 and greater increases in A4 in Hs vs. NHWs Low birth weight is associated with an increased risk of type 2 diabetes but the mechanisms behind this association are poorly understood. We aimed to investigate the association between birth weight and parental diabetes in the UK Biobank population study of 500,000 individuals. We used linear regression to test associations between reported parental type 2 diabetes and birth weight in individuals of European descent (n=257,715). We used logistic regression to investigate the association between participants’ birth weight and subsequent risk of developing type 2 diabetes. Of 257,715 individuals born as singletons and providing birth weight data, 6,872 were defined as having type 2 diabetes, 20,968 individuals reported a history of maternal diabetes (but no paternal history), 20,521 individuals reported a history of paternal diabetes (but no maternal history) and 2,754 participants reported both parents as having diabetes. Type 2 diabetes was associated with lower birth weight. A one standard deviation increase in birth weight (~500g give exact SD) was associated with a reduced risk of type 2 diabetes (Odds ratio: 0.75 [95%CI: 0.72, 0.77]; P=1x10-55). Paternal diabetes was associated with reduced birth weight (32g reduction [95%CI: 25, 32g]; P=1.6x10-23) relative to individuals with no parental diabetes. Maternal diabetes was associated with increased birth weight (38g increase [95%CI: 32, 44]; P=6.2x10-36). In summary, data from the UK Biobank provides the strongest evidence by far that paternal diabetes is associated with lower birth weight. Our findings are consistent with a role of genetic factors in determining both fetal growth and adult diabetes and cast doubt on the likely success of interventions aiming to reduce the prevalence of type 2 diabetes by improving intrauterine nutrition. Supported by: NIDDK (U01DK048489), (R01DK083297), (R01DK53061), (GCRCRR00211), (K23DK071552) Supported by: Diabetes UK ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A403 POSTERS Using data from the Coronary Artery Risk Development in Young Adults study (1995, 2000, and 2005), we examined the association between depressive symptoms, measured by the Centers for Epidemiologic Studies Depression (CES-D) Scale score, and incident diabetes (DM) and possible variation by race. The 3580 study participants (mean age 34.9, standard deviation 3.6 years) were free of DM in 1995. We defined incident DM by a self-reported physician diagnosis of DM, use of DM drugs, or fasting plasma glucose values ≥ 126 mg/dL. We used Cox regression models to determine the hazard ratio (HR) of DM by CES-D score ( <16 and ≥ 16) at baseline, adjusted for race, age, systolic and diastolic blood pressure, total cholesterol, HDL, LDL, triglycerides, and CES-D score*race interaction. Other potential covariates, such as body mass index, sex, and education, were not considered because they were highly correlated with depression, and depression was the focus of our study During the 10-year period, the cumulative incidence of DM was 4.9% among participants with CES-D score < 16 and 7.3% among those with score ≥16 (p= 0.01). The interaction term between CES-D score and race was statistically significant (p=0.02), indicating that the response to depression differed between whites and blacks. Among blacks, the cumulative incidence of DM was 7.9% and 7.6%, respectively, among those with CES-D score ≥16/<16 (p=0.84). In whites, 6.0%/2.7% of those with CES-D ≥16/<16, respectively, developed DM (p<0.01). In the un-adjusted model, among whites, the hazard ratio of DM for participants with CES-D score ≥16 was 2.29 [95% confidence interval: 1.30-4.03], compared to those with CES-D score <16. Among blacks, the HR was 0.98 [0.65-1.46]. After adjustment, the HR in whites and blacks was 2.17[1.82-2.60] and 1.15[0.78-1.71], respectively. In CARDIA participants, the effect of depressive symptoms on incident DM differs by race; depressive symptomatology was a significant predictor of incident DM only among whites. Epidemiology/ Genetics XUANPING ZHANG, GIUSEPPINA IMPERATORE, LAWRENCE E. BARKER, GLORIA L. BECKLES, DESMOND E. WILLIAMS, ANN L. ALBRIGHT, KAI MCKEEVER BULLARD, EDWARD GREGG, Atlanta, GA POSTERS Epidemiology/ Genetics EPIDEMIOLOGY—OTHER 1546-P 1548-P Potassium and Glucose Metabolism in Older Adults: The Cardiovascular Health Study Cohort The Impact of Past Severe Hypoglycemic Events on the Risk of Future Events in the United States RANEE CHATTERJEE, MARY LOU BIGGS, IAN DEBOER, LAURA SVETKEY, FREDERICK BRANCATI, JOSHUA BARZILAY, LUC DJOUSSE, JOACHIM IX, JORGE KIZER, DARIUSH MOZAFFARIAN, DAVID SISCOVICK, DAVID EDELMAN, KENNETH MUKAMAL, Durham, NC, Seattle, WA, Baltimore, MD, Tucker, GA, Boston, MA, San Diego, CA, Bronx, NY MICHAEL L. GANZ, QIAN LI, NEIL S. WINTFELD, YUAN-CHI LEE, VERONICA ALAS, JOANNA C. HUANG, Lexington, MA, Princeton, NJ History of severe hypoglycemia (SH) is a known risk factor for future events. To estimate the real-world impact of past SH events, we analyzed a sample of 7,271 adults (mean age: 61) with type 2 diabetes initiating basal insulin in 2008-2011 using a major electronic health records (EHR) database. Because we used medical records data, we defined SH events based on diagnosis codes and blood glucose measurements ≤40 mg/dL. We assumed a 16-week titration period that started upon basal insulin initiation; all analyses focused on the post-titration period. We used logistic regression to estimate the association of SH during the first 3 months on the risk of SH in the next 9 months. To account for the temporal ordering of SH events and the impact of patients’ time-varying SH histories, we also used repeated measures logistic regression to estimate the dynamic association of SH during any 3-month period on the risk of SH in the subsequent 3 months. All results were adjusted for patient demographic and clinical characteristics, including use of OADs during the year before insulin initiation. Based on the first logistic model, we found that patients who had SH during the first 3 post-titration months were more likely to have ≥ 1 SH event during the next 9 months than those who did not (probability: 45% vs. 6%; odds ratio [OR]: 13.7, p<0.01). We also found a significant dynamic association. Patients who had SH during any (post-titration) 3-month period were more likely to have ≥ 1 SH event during the subsequent 3 months than those who did not (probability: 15% vs. 1%; OR: 14.7, p<0.01). These results suggest that the impact of past SH events on the risk of future SH may not be minor as well as the potential value of preventing SH among high-risk patients. For example, using previously estimated quarterly costs for patients with and without SH events ($3,613 and $484), our repeated measures results imply that preventing one SH event may be associated with 2.2 fewer annual events and with annual costs savings of $6,733. In middle-aged cohorts, low levels of serum and dietary potassium (K) have been associated with increased diabetes risk, but their impact on other populations and on glucose metabolism is unknown. We examined associations of serum and dietary K with measures of insulin sensitivity and risk of incident diabetes among 4754 participants in the Cardiovascular Health Study, a community-based cohort of older American adults aged ≥ 65 years. We calculated the Matsuda insulin sensitivity index (ISI) using oral glucose tolerance test data from the baseline exam. Diabetes was defined as a fasting glucose ≥ 126 mg/dL, nonfasting glucose >=200, or use of diabetes medications. We used linear regression to assess the relationship of baseline K and ISI, and Cox regression to evaluate the association between baseline K and incident diabetes. All models were adjusted for age, race, sex, clinic site, BMI, waist circumference, physical activity, smoking status, alcohol use, systolic blood pressure, ACE-inhibitor and diuretic use; dietary K models were additionally adjusted for diet score and total energy intake. Participants with a serum K <4.0 mEq/L had an adjusted mean difference in Matsuda ISI of -0.22 (-0.43, -0.01) compared to those with a serum K ≥4.5. Participants in the lowest quartile of dietary K intake had a corresponding adjusted mean difference in Matsuda ISI of -0.61 (-0.94, -0.29) compared to the highest quartile. A total of 445 cases of incident diabetes occurred over a median follow-up of 12 years. In multivariate models, neither serum nor dietary K was associated with diabetes risk, with a HR (95% CI) of 1.00 (0.74-1.35) for serum K <4.0 mEq/L compared to ≥4.5. Among older adults, low-normal serum and low dietary K were associated with decreased insulin sensitivity, but not with diabetes risk. Additional study in older adults is needed to clarify the associations between low serum and dietary K with insulin resistance and diabetes risk. 1549-P Age-Specific Changes in Diabetes Incidence and Mortality among U.S. Adults, 1990–1994 to 2000–2004 1547-P YILING J. CHENG, TED THOMPSON, XIAOHUI ZHUO, GUISSEPINA IMPERATORE, LAWRENCE BARKER, LINDA S. GEISS, EDWARD GREGG, Atlanta, GA OGTT Modeled β-Cell Function Measures Predict the Development of Type 2 Diabetes in Japanese Americans The increase in diabetes (DM) prevalence depends on the magnitude of increase in DM incidence in the general population and the magnitude of decrease in mortality in the diabetes population. We used National Health Interview Survey data to compare changes from 1990-1994 to 2000-2004 in the age-specific incidence of DM among adults aged 20 to 84 years and mortality in those with DM. Incident DM was defined as a self-report of DM diagnosed in previous 12 months. Logistic regression with a cubic term for age was used to model age-specific incidence and prevalence. Piecewise exponential regression with a quadratic age term was used to model agespecific mortality. During the 10-year interval between two survey periods, the age-sex-race/ethnicity adjusted prevalence increased 61.4% (from 4.1% to 6.9%), the adjusted annual incidence increased 68.2% (from 0.44% to 0.74%) and the adjusted annual mortality among the diabetic population decreased 11.1% (from 1.8% to 1.6%). The figure below shows the magnitude of changes in incidence and mortality when expressed in terms relevant to their impact on prevalence. These findings suggest that for most of the age spectrum, increases in incidence affected increases in prevalence more than decreases in mortality. Therefore, although mortality rates will likely continue to affect DM prevalence, especially among the oldest segment of the population, reducing incidence through preventive intervention is crucial to reducing prevalence. KRISTINA M. UTZSCHNEIDER, ANNA LARGAJOLLI, ALESSANDRA BERTOLDO, DONNA L. LEONETTI, MARGUERITE J. MCNEELY, WILFRED Y. FUJIMOTO, CLAUDIO COBELLI, STEVEN E. KAHN, EDWARD J. BOYKO, Seattle, WA, Padova, Italy Decreased β-cell function is a key feature of type 2 diabetes (T2DM). C-peptide modeling of OGTT data is being used to estimate β-cell function. We sought to determine if modeled measures of β-cell function can predict the development of T2DM and how they compare with already established measures. OGTTs (time points: 0, 30, 60 and 120 min) were performed on 658 Japanese-American subjects (136 with T2DM) at baseline. Those without T2DM at baseline were followed for up to 10 years for development of incident diabetes. Modeling was successfully performed on 461 subjects. After excluding outliers and those with missing or negative values, baseline data from 426 subjects (n=180 NGT, n=179 IFG/IGT and n=67 T2DM) (318M/108F; age mean±SD: 50.5±11.7 y) were analyzed. β-cell function measures included the insulinogenic index (ΔI/ΔG from 0-30 min) and model-derived β-cell responsivity indices (Φstatic, Φdynamic, Φtotal). The ability of each measure to predict incident T2DM was estimated in logistic regression models adjusted for age, sex, BMI, family history of T2DM, and insulin sensitivity (using a model derived measure for the Φ measures and the Matsuda Index for ΔI/ΔG). At baseline all β-cell function measures were significantly higher in NGT, intermediate in IFG/IGT and lower in T2DM. Of the 359 subjects without T2DM at baseline, 62 developed diabetes over 10 years. In adjusted logistic regression models, only Φ dynamic and ΔI/ΔG predicted T2DM at 10 yrs (odds ratio per 1 unit change [95% CI]: ln Φ dynamic 0.29 [0.13-0.64] p=0.002; lnΔI/ ΔG 0.24 [0.13-0.46] p<0.001,), but Φ static and Φ total did not. Area under ROC curves did not differ for Φ dynamic (0.83) and ΔI/ΔG (0.83) in the ability to predict T2DM. We conclude that of modeled β-cell function measures from a standard OGTT, only Φ dynamic predicts diabetes development and was equivalent to the insulinogenic index in this regard. Modeling of β-cell function may perform better with inclusion of more early time points than those collected in this study. & For author disclosure information, see page 829. A404 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—OTHER 1550-P 1552-P Fasting Insulin Levels Predict Incidence of Diabetes among American Young Adults: The CARDIA Study Maintained Fitness May Especially Benefi t Young Adults With High BMI & Insulin Resistance: The CARDIA Study PENGCHENG XUN, KIANG LIU, WENHONG CAO, MARTHA DAVIGLUS, CATHERINE LORIA, MICHAEL STEFFES, DAVID R. JACOBS, KA HE, Bloomington, IN, Chicago, IL, Chapel Hill, NC, Bethesda, MD, Minneapolis, MN LISA S. CHOW, DAVID R. JACOBS, MERCEDES CARNETHON, BARBARA STERNFELD, LYNN E. EBERLY, ERIN AUSTIN, NA ZHU, STEPHEN SIDNEY, CLAUDE BOUCHARD, PAMELA J. SCHREINER, Minneapolis, MN, Chicago, IL, Oakland, CA, Baton Rouge, LA Background: Experimental studies in animals have shown that hyperinsulinemia is necessary for diet-induced obesity and insulin resistance, a precursor of type 2 diabetes mellitus. However human studies are lacking. Research design and methods: A cohort of 3,429 American young adults, aged 18-30 years, free of diabetes in 1985-86 (baseline), was enrolled in CARDIA and attended up to 7 follow-up examinations through 2010-11 (Year 25). Fasting glucose were assessed by a hexokinase method. Fasting insulin was assessed by several methods, each calibrated to an isotope dilutionliquid chromatography/tandem mass spectrometry method that used purified recombinant insulin as its standard. Incident diabetes was identified by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1C levels and/or anti-diabetic medications. Results: Medians of cumulative average insulin levels were 5.95, 7.55, 8.84, 10.79 and 15.25 µU/mL across five groups (fasting insulin: <7 µU/mL (about 1/3 of the sample); quartiles for insulin ≥7). During the 25-year followup, 394 incident cases were identified. Covariates were age, sex, race, study center, education, smoking, alcohol consumption, physical activity, family history of diabetes, BMI, LDL/TC, HDL/TC, systolic blood pressure and baseline glucose concentration. Insulin grouping and covariates were time dependent. Hazard ratios (95% confidence intervals) for incident diabetes from the lowest to highest groups of insulin levels were 1.00, 1.26 (0.68, 2.34), 1.86 (1.06, 3.25), 3.67 (2.17, 6.21) and 7.05 (4.13, 12.04); Ptrend<0.001. The positive association persisted in each gender/ethnicity/weight status subgroup. Conclusions: Fasting insulin levels or hyperinsulinemia was positively associated with incidence of diabetes for men and women, African Americans and Caucasians, and normal weight or overweight. Early fasting insulin ascertainment may help clinicians identify those at high risk of diabetes later in life. 1551-P Mortality among Veterans With Type 2 Diabetes Initiating Metformin, Sulfonylurea, or Rosiglitazone Monotherapy Supported by: N01-HC95095, N01-HC48047,N01-HC48048, N01-HC48049, N01HC48050 EDWARD J. BOYKO, STEPHANIE WHEELER, KATHRYN MOORE, CHRISTOPHER W. FORSBERG, KEVIN RILEY, JAMES S. FLOYD, NICHOLAS L. SMITH, Seattle, WA Aims/hypotheses: Oral hypoglycemic medications are the most commonly used type 2 diabetes pharmacologic treatments. Despite their frequent use, existing research is limited on their comparative safety and in particular their effects on overall mortality. We compared mortality risk with monotherapy initiation of four oral hypoglycemic medications in a nationwide cohort of U.S. veterans with type 2 diabetes. Methods: We identified new monotherapy oral diabetes medication users between 2004-2009 who received care for at least one year from the Veterans Health Administration. Patients were followed until initial monotherapy discontinuation, addition of another diabetes pharmacotherapy, death, or end of follow-up (December 31, 2009). Mortality hazards ratios (HR) were estimated using Cox regression adjusted for potential confounding factors. Results: New users of metformin, sulfonylureas, and rosiglitazone numbered 193,172 (mean age 63.4 yrs, 95.9% male), of whom 4,256 (2.2%) died during the study period. Metformin was prescribed most frequently (68%), followed by glipizide (15%), glyburide (15%), and rosiglitazone (2%). Mean duration of use for each medication was 1.4-1.7 years. Adjusted HR for sulfonylurea or rosiglitazone monotherapy compared with metformin monotherapy were as follows: glyburide (HR 1.38, 95% CI, 1.27-1.49); glipizide (HR 1.58, 95% CI, 1.46-1.70); and rosiglitazone (HR 1.26, 95% CI, 1.02-1.56). Glipizide monotherapy was associated with a higher risk of mortality compared to rosiglitazone (HR 1.25, 95% CI 1.01-1.56) or glyburide monotherapy (HR 1.15, 95% CI 1.05-1.25). Risk of mortality did not significantly differ between glyburide compared to rosiglitazone monotherapy (HR 1.09, 95% CI 0.88-1.36). Conclusions/interpretations: Significantly higher mortality was associated with the use of glyburide, glipizide, or rosiglitazone compared to metformin, and with the use of glipizide compared with rosiglitazone or glyburide. ADA-Funded Research & 1553-P Diabetes as a Predictor of Survival in Metastatic Nasopharyngeal Carcinoma XIAO YE, YING JIN, YUBO XING, YINGXIANG SONG, LIJUN WANG, LIZHONG SU, YIPING ZHANG, YANYIN HUA, Hangzhou, China Epidemiologic and clinical evidence suggests that diabetes may associate with the occurrence and prognosis of many types of cancer. However, the relationship between diabetes and metastatic nasopharyngeal carcinoma (NPC) is still unknown. The aim of this study is to explore the role of diabetes on metastatic NPC patients. 405 patients with metastatic NPC referred to two teaching hospitals in China were retrospectively analyzed. The Kaplan-Meier method was used to compare survival curves for patients with and without diabetes. Univariate and multivariable analyses were performed using the Cox proportion hazard model to estimate hazard ratio for prognostic factors. Factors analyzed included general characteristics (age, sex and performance status), LDH level, presence of metastasis at presentation, specific metastatic sites, DFI, anemia and diabetes status. The overall survival (OS) in patients with diabetes was lower than those without diabetes (median OS is 20 months for diabetes and 15.5 months for nondiabetes,P <0.001 ). Independently prognostic factors included performance status, LDH level and the presence of diabetes. After adjusted by other prognostic factors, patients with diabetes had 34% excess risk (P = 0.006) of all-cause mortality compared to those non-diabetes patients. We found diabetes is an indicator of poor outcome for patients with metastatic NPC. Prevention and treatment of diabetes may contribute to the improvement of prognosis for these patients. For author disclosure information, see page 829. Guided Audio Tour poster A405 POSTERS Epidemiology/ Genetics Decreased fitness is associated with higher weight & waist girth; whether this association is influenced by body mass index (BMI) & insulin resistance (IR) remains unknown. Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study without year (Y) 0 diabetes [n=2048, 43.4% men, Y0 (1985) age 18-30] who had fitness measured longitudinally (Y0,Y20) by treadmill were classified by Y0 BMI [normal: nBMI < 25 vs high: hBMI≥25] & Y0 HOMAIR [Insulin Sensitive (IS): HOMA-IR <1.84 (75%tile) vs Insulin Resistant (IR): HOMA-IR≥1.84] into nBMI/IS, hBMI/IS, nBMI/IR, hBMI/IR. Fitness change was classified by change in sex-specific treadmill time (Y20-Y0): Maintained Fitness [increase or decline ≤20%tile] or Decreased Fitness [decline >20%tile]. Association of fitness change with each of weight & waist girth (Y20 & Y25) was assessed by multiple linear regression. Within each Y0 BMI/IR group, those who maintained fitness had lower weight & waist girth at Y20 & Y25 compared with those who decreased fitness (Table 1). The overall interaction between Y0 BMI/IR & fitness change was significant for: Y20 weight (p<0.01), Y20 waist girth (p <0.01) & Y25 weight (p <0.01); the hBMI/IR group had the largest differences in weight & waist girth between fitness categories. Young adults, particularly those with high BMI & IR, who maintained fitness had less middle age weight gain & waist girth compared with young adults who decreased fitness. EPIDEMIOLOGY—OTHER 1555-P Urinary Bisphenol A Concentrations and Glucose Metabolism in Adolescents ELLEN M. WELLS, LEILA W. JACKSON, MICHAELA B. KOONTZ, Cleveland, OH Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical which has been associated with adverse metabolic outcomes including diabetes and insulin resistance in adults. Our objective was to examine the association between urinary BPA concentrations and measures of glucose homeostasis and insulin resistance in children using National Health and Nutrition Examination Survey 2003-2010 data. The main outcomes were fasting glucose, hemoglobin A1C (HbA1C), and fasting insulin. The outcomes and BPA were not normally distributed and were thus log-transformed or described using quartiles. Complete data were available for 1,759 individuals aged 12-18 years, including 822 who had fasting laboratory data; laboratory measures were not obtained in individuals younger than 12 years of age. In models adjusted for urinary creatinine, age, sex, race/ethnicity, education, and smoking status, no significant associations were found between BPA concentrations and any of the outcome measures (Table). In conclusion, there were no significant associations between BPA exposure and measures of glucose metabolism or insulin resistance in this cross-sectional analysis of adolescents, which is in contrast with recent epidemiologic studies in adults. This may indicate that BPA-related disruption of glucose-insulin homeostasis develops over time or is influenced by life stage. Longitudinal studies are needed to further examine this relationship. Adjusted percent change (95% confidence interval) for glucose metabolism markers with increasing BPA BPA quartile Glucose (N=822) HbA1C (N=159) Insulin (N=813) Quartile 1 (<LOD to 1.4 ng/mL BPA) Referent Referent Referent Quartile 2 (1.5 to 2.7 ng/mL BPA) -1.01 (-4.16, 2.25) -0.60 (-1.81, 0.63) 3.53 (-12.81, 22.94) Quartile 3 (2.8 to 5.3 ng/mL BPA) 0.63 (-2.77, 4.14) -0.94 (-2.13, 0.27) -2.04 (-17.05, 15.67) Quartile 4 (5.4 to 193 ng/mL BPA) 0.85 (-3.10, 4.95) 0.53 (-0.84, 1.92) -4.97 (-18.98, 11.47) 1554-P POSTERS Epidemiology/ Genetics Association of Differential White Blood Cell Count With Insulin Resistance and β-Cell Dysfunction—The PROMISE Cohort CHRISTINE C. LEE, STEWART B. HARRIS, RAVI RETNAKARAN, HERTZEL C. GERSTEIN, BRUCE A. PERKINS, BERNARD ZINMAN, ANTHONY J. HANLEY, Toronto, ON, Canada, London, ON, Canada, Hamilton, ON, Canada Higher white blood cell count (WBC) is associated with incident type 2 diabetes (T2DM), but little is known on the role of differential WBC in insulin resistance and β-cell dysfunction. We examined the cross-sectional associations of granulocytes, lymphocytes and monocytes with insulin resistance and β-cell dysfunction in 712 non-diabetic participants in the PROMISE (Prospective Metabolism and Islet Cell Evaluation) cohort. Differential WBCs were measured in fasting samples with granulocytes consisting of basophils, neutrophils and eosinophils. Insulin resistance was measured by Matsuda’s insulin sensitivity index (ISOGTT) and homeostasis model assessment of insulin resistance (HOMA-IR), while β-cell dysfunction was measured by insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and Insulin Secretion Sensitivity Index-2 (ISSI-2). We used multiple regression models to examine the association of each WBC subtypes with outcome measures, adjusting for demographics, smoking, family history of diabetes and BMI. All WBC subtypes were inversely associated with ISOGTT (β= -0.12 [-0.15, -0.080] for granulocytes, β= -0.24 [-0.32, -0.16] for lymphocytes, β= -0.67 [-0.99, -0.34] for monocytes), and positively associated with HOMA-IR (β= 0.11 [0.070, 0.14] for granulocytes, β= 0.22 [0.14, 0.30] for lymphocytes, β= 0.66 [0.33, 0.99] for monocytes, all p<0.001). Granulocytes and lymphocytes were inversely associated with ISSI-2 (β= -31.3 [-51.3, -11.3], β= -84.4 [-128, -40.5] respectively, all p<0.001). An initial significant association of monocytes with ISSI-2 was no longer significant after adjusting for BMI (β= -20.1 [-199, 159]). WBC subtypes were not associated with IGI/IR. In conclusion, granulocytes and lymphocytes were independently associated with insulin resistance, but association with β-cell dysfunction could not be confirmed. Our data is consistent with the literature on the link between inflammation and metabolic disorders for T2DM. Supported by: Case Western Reserve University (to M.B.K.); NIH (U01-HL-103622 to M.B.K.) 1556-P Cognitive Function and the Risk for Diabetes among Young Men GILAD TWIG, ISRAEL GLUZMAN, AMIR TIROSH, GAL YANIV, ARNON AFEK, ARI SHAMISS, ESTELA DERAZNE, DORIT TZUR, BARAK GORDON, EYAL FRUCHTER, TALI CUKIERMAN-YAFFE, Ramat Gan, Israel, Boston, MA, Tel Hashomer, Israel, Tel Aviv, Israel Objective: The association between cognitive function within normal range and the risk for diabetes among young men is unknown. Research Design & Methods: General Intelligence Score (GIS) was assessed by a 9-point scale among men that were part of the MELANY cohort of the Israeli Defense Forces between January 1st 1995 and December 31th 2010. GIS was assessed at the age of 17.4 years and was based on language ability and intellectual performance (>80% correlation with the Wechsler IQ scale). Excluded were participants with a history of diabetes or those with a follow up shorter than 2 years, yielding a total of 35,500 men that were included in final analysis. Results: During 220,265 person-years of follow-up, 770 new cases of diabetes were diagnosed. A multivariate model adjusted for age, BMI, family history of diabetes, physical activity, socioeconomic status, smoking, education level, birth country, country of origin, triglyceride level and WBC count revealed a 10.7% increase in incident diabetes for every unit decrement in GIS (p<0.001). Cox proportional hazard functions for the latter multivariable model is shown in figure 1a. General linear models showed that the onset of diabetes was different between the groups; the onset of diabetes among the highest GIS group was delayed by 2.03 years (95%CI=0.042-4.033 years, p=0.042) as compared to the lowest GIS (Fig. 1b). Conclusions: Cognitive function that is well within the normal range is an independent risk factor for diabetes in young men. Supported by: CDA & For author disclosure information, see page 829. A406 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—OTHER 1558-P Association between Colchicine Use and Risk of Incident Diabetes among Veterans With Gout Supported by: Talpiot Medical Leadership Program Supported by: Takeda Pharmaceuticals U.S.A., Inc. 1557-P 1559-P Rates and Costs of Severe Hypoglycemic Events in Type 2 Diabetes in the United States: Findings from a Systematic Literature Review and Electronic Health Records The Ethiopian Experience With Diabetes after Immigration to Israel ANAT JAFFE, ANNE E. SUMNER, SHMUEL M. GIVEON, Hadera, Israel, Bethesda, MD, Tel Aviv, Israel MICHAEL L. GANZ, YINGXIN XU, NEIL S. WINTFELD, QIAN LI, YUAN-CHI LEE, MICHAEL J. BYRNES, AJIBADE O. ASHAYE, ELYSE GATT, JOANNA C. HUANG, Lexington, MA, Princeton, NJ Mass migration of Jewish Ethiopians to Israel began abruptly in 1984. On arrival in Israel, undernourishment was common and type 2 diabetes (DM) occurred in <1% of immigrants. Years after arrival in Israel and with exposure to urban-industrial lifestyles, DM is now common in Ethiopian Israelis. It is unknown if the long term consequences of DM differ in Ethiopians vs. other Israelis. From 2003 to 2012, a prospective study of 223 diabetic Israelis (34% Ethiopian, 44% male, age 62±13y, mean±SD) receiving health care at the Clalit Health Services, the largest HMO in Israel, was undertaken. By 2 to 1 non-Ethiopians were matched to Ethiopians by age and sex. Compared to non-Ethiopian Israelis, Ethiopian Israelis had shorter citizenship period (15±3 vs. 40±13y, P<0.01), shorter duration of DM (5±4 vs. 10±8y, P<0.01), lower BMI (24.8±4.0 vs. 30.2± 5.0, P<0.05), lower rate of smoking (3% vs. 52%, P<0.01) and less volitional physical activity (15% vs. 42%, P<0.01). In addition, at baseline and 10y, compared to non-Ethiopians, Ethiopians had less hypertension and less dyslipidemia. Furthermore after 10y of follow-up, Ethiopian diabetic Israelis were more healthy than non-Ethiopian diabetic Israelis because Ethiopians had less neuropathy, nephropathy, retinopathy, ischemic heart disease and peripheral vascular disease. In addition, the 10y death rate was lower in Ethiopians than non-Ethiopians (13% s. 36%, P<0.01). Determinants of less severe diabetic complications in Ethiopians vs. other Israelis include: healthier lifestyle prior to immigration, less smoking, lower BMI, migration selectivity , and possibly a lower genetic risk profile. It is a key goal in Israel to maintain the best possible health in future generations of Ethiopians born in Israel. Severe hypoglycemic (SH) events have frequently been assessed, but few reports have focused on basal insulin-treated type 2 diabetes (T2D) patients. To study real-world rates and costs of SH in this population we conducted two complementary studies: a systematic literature review and an analysis of adults with T2D initiating basal insulin in 2008-2011 using a major electronic health records (EHR) database. The EHR included physician and hospital encounters and laboratory test results. Because we used medical records data, we defined SH events based on diagnosis codes and blood glucose measurements ≤40 mg/dL. The systematic review identified 8 studies of the target population (9 patient cohorts) that reported SH incidence and 9 studies (14 patient cohorts) that reported total SH event rates. The literature showed median incidence and total SH event rates of 6.5 and 16.5 per 100 patient-years, respectively. These results were similar to those of the EHR analysis where the incidence and total SH event rates were 5.0 (95% confidence interval [CI]: 4.5-5.3) and 9.3 (95% CI: 8.6-10.0) per 100 patient-years, respectively. Only 3 articles reported SH-related costs, which ranged from $1,049-$1,678 per event. The average SH event cost derived from the EHR was similar ($1,891; 95% CI: $1,124-2,657). We also examined total healthcare costs (SH-related plus all other medical costs) using the EHR. Due to the variable lengths of follow-up across patients, we analyzed quarterly, rather than annual costs. Patients with ≥1 SH event had greater average quarterly healthcare costs, adjusted for patient demographic and clinical characteristics, including use of metformin, sulfonylureas, and other OADs, than patients without any SH event ($3,613 [95% CI: $1,196–6,050] vs. $484 [95% CI: $445–527]; p<0.01). These results suggest that real-world SH incidence and total event rates and costs among basal insulin-treated T2D patients are significant. ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A407 POSTERS This retrospective study aimed to examine the association between colchicine use and incidence of type 2 diabetes among 27,876 veterans with gout (ICD-9-CM codes: 274.xx) in Veterans Affairs veterans integrated services network (VISN 16) with up to 11 years of follow-up. Diabetes defined by ICD-9-CM codes (250.xx) or any use of anti-diabetic medications was required to not occur prior to the first recorded gout diagnosis (index diagnosis). Propensity score (PS) 1:1 matching was employed for 9,965 colchicine users and 17,911 non-colchicine users. The final study sample was 1,046 pairs of PS matched patients with comparable one-year baseline variables (all p-values>0.05). Time to the incident diabetes from the index diagnosis was modeled by Poisson model, Cox Proportional Hazard (PH) model, and time-varying Cox (PH) model, controlling for one-year baseline information (e.g., age, gender, race, index year, body mass index, serum uric acid, anti-gout drug use and healthcare utilization). The duration and dosage of colchicine were also specified in the models. Among the 1,046 matched pairs, 234 colchicine users and 224 non-colchicine users had records of incident diabetes (i.e., incidence rates of 38.95 per 1000 patientyears and 39.02 per 1000 patient-years, respectively). In Poisson and Cox (PH) regressions, the risk of incident diabetes was reduced with increased duration of colchicine use, but the overall difference across quartiles of colchicine duration was not statistically significant. In time-varying analysis with adjustments for confounding factors, the hazard ratio for incident diabetes among colchicine users was 0.877 (95% confidence interval: 0.6621.163) compared with non-colchicine users. In summary, the trend toward and moderate reduced risk of diabetes among colchicine users appear to be associated with an increased duration and dose of colchicine use in patients with gout. Further studies are warranted to focus on the patients with high intensity of colchicine exposure. Epidemiology/ Genetics LIZHENG SHI, LIYA WANG, YINGNAN ZHAO, QIAN SHI, VIVIAN FONSECA, New Orleans, LA, Wilmington, DE, Hartford, CT EPIDEMIOLOGY—OTHER Physical inactivity is prevalent among middle-aged and older Americans with diabetes and prediabetes, and this prevalence was decreased by nearly half in 4 years. Effort to improve and sustain physical activity over time is urgently needed. 1560-P Low Eradication Rate of Helicobacter Pylori (HP) in Patients With Diabetes: A Meta-Analysis CHIKA HORIKAWA, SATORU KODAMA, SAKIKO YOSHIZAWA, KAZUYA FUJIHARA, RYOKO TAJIMA, YOKO YACHI, AKIKO SUZUKI, OSAMU HANYU, HITOSHI SHIMANO, HIROHITO SONE, Tsukuba, Japan, Mito, Japan, Niigata, Japan, Tokyo, Japan 1562-P The Role of Neighborhood Socioeconomic Status in Racial/Ethnic Disparities in Type 2 Diabetes REBECCA S. PICCOLO, ANDRE B. ARAUJO, JOHN B. MCKINLAY, Watertown, MA Racial/ethnic disparities in type 2 diabetes (T2D) are a major public health problem with black and Hispanics at a greater risk relative to whites. The search for contributors to disparities in T2D tends to focus on three major areas of research: (1) lifestyle and behavioral risk factors, (2) early biochemical changes, and (3) genetics. We hypothesize two additional, complementary, contributors to racial/ethnic disparities: (4) individual and (5) neighborhood level socioeconomic factors. Participants were drawn from the Boston Area Community Health (BACH) Survey, a racially/ethnically diverse, longitudinal epidemiologic study of community-dwelling residents of Boston. Participants’ residential addresses were geo-coded and merged with neighborhood-level data obtained from the US Census. Within this cohort, we identified 2732 subjects without diabetes at baseline who were followed for diabetes incidence. The inperson interview included validated questionnaires on demographics, health care access/utilization, lifestyles, health status and behaviors, physical measures, and biochemical parameters. In age-, gender-, and BMI- adjusted models, black and Hispanic participants were twice as likely to develop T2D over the 7 year study period (black: OR=2.27, 95% CI [1.30-3.97]; Hispanic: 1.91, [ 1.14-3.18]) versus white participants. Individual socioeconomic status attenuated these results considerably (black: OR=1.67, [0.94-2.96], Hispanic: 1.26, [0.73-2.17]). There were significant differences in the incidence of T2D by neighborhood (p=0.03) even after adjustment for individual race/ethnicity, age, gender, BMI and SES. However, adjustment for neighborhood SES did not attenuate the racial/ ethnic disparities further. While studies of neighborhood contributions appear promising, their contribution to disparities remains uncertain. Further, there is a need to identify specific characteristics of neighborhoods that explain disparities in disease. POSTERS Epidemiology/ Genetics In general, diabetic patients are more resistant to antibiotics than non-diabetic individuals causing a prolongation of infectious diseases. However, it is controversial whether diabetes affects the eradication rate of HP. We conducted a systematic review and meta-analysis to compare the eradication rate between diabetic and non-diabetic individuals. Electronic literature searches using Biosis, MEDLINE, Embase, PASCAL, and SciSearch were conducted for studies on eradication of HP and that presented data on individuals undergoing eradication treatment for HP and achieving HP eradication according to the presence of diabetes. The difference in eradication rate was pooled with a random-effects model. We analyzed 7 eligible studies. The Figure shows the difference in the eradication rate between those with and without diabetes with the 95% confidence interval (CI). Overall, patients with diabetes had an 18% lower eradication rate than non-diabetic individuals (P=0.008). A lower eradication rate was also observed in 2 studies of type 1 diabetes vs. non-diabetes (-12%, P=0.08) and 4 studies of type 2 diabetes vs. non-diabetes (-25%, P=0.008). Results of this meta-analysis showed that the eradication rate for HP was lower in diabetic than in non-diabetic individuals. Therefore, diabetic patients might be at risk for persistent prolongation of gastrointestinal tract symptoms and at high risk of gastric cancer, in particular, MALT lymphoma. Supported by: NIH/NIDDK (U01DK056842), (R01DK080786) 1563-P Predicting Incident Type 2 Diabetes by Insulin Sensitivity Index using Reclassification YUKIKO ONISHI, TOMOSHIGE HAYASHI, KYOKO K. SATO, MARGUERITE J. MCNEELY, DONNA L. LEONETTI, STEVEN E. KAHN, WILFRED Y. FUJIMOTO, EDWARD J. BOYKO, Tokyo, Japan, Osaka, Japan, Seattle, WA 1561-P Physical Activity in U.S. Adults With Diabetes and Prediabetes, 2006-2010 We sought to determine which insulin sensitivity index best predicted future type 2 diabetes (T2DM). We followed 398 non-diabetic Japanese Americans for 10-11 years for the development of T2DM defined by the American Diabetes Association 1997 criteria using a 75-g oral glucose tolerance test (OGTT). At baseline we measured the following insulin sensitivity indices: fasting plasma insulin or C-peptide concentration, HOMA-IR, QUICKI, fasting insulin/glucose ratio, 2-hr insulin, 2-hour insulin/ glucose ratio, area under the insulin curve for a 2-hr OGTT (AUC insulin), insulin sensitivity index (ISI) [10000/(fasting glucose x fasting insulin)], 2-hr ISI [10000/(2-hr glucose x 2-hr insulin)], and indices by Duncan, Stumvoll, Gutt, Avignon, and Matsuda. We examined which index best improved a multiple logistic regression model predicting incident T2DM that included age, gender, family history of T2DM, BMI, and fasting glucose. Improvement was evaluated by category-free net reclassification improvement (cfNRI) and integrated discrimination improvement (IDI). There were 84 incident cases of T2DM. Gutt index (= m/(mean of fasting and 2-hr glucose)/log (mean of fasting and 2-hr insulin), m = [75,000 + (fasting glucose - 2-hr glucose) x 0.19 x weight]/120) had the highest total cfNIR (0.994), which is the sum of cfNIR for events (0.548) and cfNIR for nonevents (0.446). Total cfNRI of the other indices were as follows: 2-hr ISI (0.879), Stumvoll index (0.643), 2-hr insulin (0.607), Avignon index (0.536), fasting C-peptide (0.461), 2-hr insulin/glucose ratio (0.354), Matsuda index (0.318), AUC insulin (0.259), fasting insulin (0.253), HOMA IR and Duncan index (0.245), fasting insulin/ glucose ratio(0.229), and ISI and QUICKI (0.20 0). Gutt index also had the highest IDI (0.135) of all the indices. In conclusion, Gutt index showed the best risk reclassification and improvement in discrimination of the insulin sensitivity indices that we evaluated in predicting future T2DM in Japanese Americans. PEARL G. LEE, CHRISTINE CIGOLLE, JINKYUNG HA, LILLIAN MIN, CAROLINE S. BLAUM, WILLIAM H. HERMAN, Ann Arbor, MI Physical activity (PA) on a regular-basis is essential for diabetes selfmanagement and prevention of diabetes. The objective of this study is to determine the prevalence of PA and its change over 4 years among adults with diabetes and prediabetes. We performed longitudinal analysis of the 2006-2010 waves of the Health and Retirement Study, a biennial, longitudinal, nationally representative survey. We limited the analysis to 5,352 respondents aged 53 years and older who had a measured HbA1c in 2006 and were alive in 2010. All respondents self-reported the number of days they participated in mild, moderate, and vigorous levels of physical activities. Mixed effects models were performed to compare PA changes in 4 years among respondents with normoglycemia (no diabetes history and HbA1c<5.7%), prediabetes (no diabetes history and HbA1c 5.7-6.4%), and diabetes (diabetes history or HbA1c ≥ 6.5%). In 2006. 38% of all the respondents were physically active (at least 150 minutes of moderate level PA per week), including 44%, 38%, and 30% of respondents with normoglycemia, prediabetes, and diabetes, respectively. Older age, having less education, and being obese were associated with being less active. Four years later, the prevalence of all respondents remaining physically active was decreased by 47%; the prevalence decreased by 43%, 50%, and 56% for respondents with normoglycemia, prediabetes, and diabetes, respectively. Respondents with diabetes were less likely than normoglycemic adults to perform vigorous PA (21% vs. 34%) but more likely to perform mild level PA (46% vs. 31%). Over 4 years, the odds of respondents with diabetes performing vigorous or moderate PA was 0.70 times the odds for normoglycemia (p<0.001). & For author disclosure information, see page 829. A408 Guided Audio Tour poster ADA-Funded Research 1566-P Sarcopenic Obesity Is Associated With Insulin Resistance and Cardiovascular Risk Factors in Healthy Young Adults YUNJUAN GU, XUHONG HOU, LEI ZHANG, JIE LI, YUQIAN BAO, WEIPING JIA, Shanghai, China HYUN MIN KIM, EUN YOUNG LEE, SUN OK SONG, HANNAH SEOK, JI HYE HUH, BYUNG-WAN LEE, EUN SEOK KANG, CHUL WOO AHN, HYUN CHUL LEE, BONG SOO CHA, Seoul, Republic of Korea The aim of the study was to estimate the risk of cancer and mortality in Chinese patients with type 2 diabetes mellitus (T2DM). Based on the Shanghai Diabetes Registry database linking to the Shanghai Cancer Registry and Surveillance System, a total of 12,276 T2DM were defined and followed from December 2001 to July 2011. Gender-, and age-stratified standardized incidence ratio (SIR) and mortality ratio (SMR) with 95% confidence interval (CI) were calculated using the same regional population as reference. The overall cancer risk was found significantly increased with an SIR of 3.14 (2.73-3.56) and 4.29 (3.64-4.94) in both male and female, respectively. As for site-specific cancers, risks of lung cancer, colorectal cancer, gastric cancer, liver cancer and pancreatic were significantly elevated with SIRs of 1.74 (1.13-2.34), 3.93 (2.61-5.24), 3.13 (2.06-4.21), 3.86 (2.43-5.29) and 5.46 (2.69-8.22) in male, 5.71 (3.74-7.69), 2.56 (1.30-3.81), 4.19 (2.25-6.13), 3.56 (1.15-5.97) and 9.00 (4.59-13.41) in female, respectively. Risks of prostate cancer and breast cancer were significantly increased with an SIR of 5.48 (3.01-7.05) in male and 4.60 (2.90-6.31) in female. Overall cancer mortality was significantly increased with an SMR of 2.27 (1.86-2.68) and 1.86 (1.462.26) in male and female, respectively. Regarding site-specific cancer mortality, in male T2DM, risks of gastric cancer, liver cancer and pancreatic cancer were found significantly increased with SMRs of 2.14 (1.06-3.22), 3.28 (1.85-4.71) and 4.35 (1.88-6.82), respectively. In female T2DM, risks of lung cancer and pancreatic cancer significantly were increased with SMRs of 4.90 (2.90-6.90) and 7.76 (3.83-11.69), respectively. The patients with T2DM have excess risks of cancer and mortality. Additional cancer screening should be performed in the treatment of patients with T2DM. Recently, the clinical significance of sarcopenia or sarcopenic obesity has been emphasized especially in an elderly population, however, not sufficiently in a younger population. This study aimed to investigate the association between body composition and cardiometabolic parameters in healthy young adults aged 18 to 30 years from KHANES IV conducted in 2009. Sarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by weight (%) (ASM/Wt) < 1 SD below the sex-specific mean for young adults. Obesity was defined as a body mass index (BMI) ≥25 kg/m2. The subjects were further classified into sarcopenic obesity (SO), nonsarcopenic obesity, sarcopenic nonobesity, and nonsarcopenic nonobesity groups based on both ASM/Wt and BMI. A total 1001 subjects (460 men and 541 women; mean age 25.1 ± 3.4 years) were analyzed. ASM/Wt was negatively correlated with BMI, waist circumference, total body fat mass, HOMA-IR, total cholesterol, triglyceride level, number of components of the metabolic syndrome, and Framingham risk score in both men and women. The prevalence of SO was 10.4 % in men and 7.0 % in women. Subjects with SO had a higher blood pressure, a more atherogenic lipid profile (high triglyceride and low HDL-cholesterol level), and a greater insulin resistance (high fasting blood glucose, fasting serum insulin, and HOMA-IR) than any other group. The prevalence of metabolic syndrome was 28.9 % in SO group which was much higher compared to 1 % in nonsarcopenic nonobesity group. In contrast to the previous report in an elderly population, 25-hydroxyvitamin D level was slightly higher in obese group, however, was not different between subjects with sarcopenia and those without sarcopenia. In conclusion, ASM/Wt showed significant negative correlations with various metabolic parameter and cardiovascular risk factors. And SO group was more closely associated with insulin resistance and cardiovascular risk factors even in healthy young adults. Supported by: National Basic Research Program (2011CB504001) 1565-P What Fraction of Type 2 Diabetics in the United States Meet the Recommended Levels of HDL-Cholesterol, One Half or Two Thirds? 1567-P YITING WANG, ZHONG YUAN, RACHEL WEINSTEIN, PAUL E. STANG, JESSE A. BERLIN, Titusville, NJ Prevention of Type 2 Diabetes: A Systematic Review and MetaAnalysis of Different Intervention Strategies Low HDL cholesterol (HDL-C) and high triglycerides (TG) is the most prevalent pattern of dyslipidemia in patients with type 2 diabetes (T2D). A study using the National Health and Nutrition Examination Surveys (NHANES) reported that 69.0% and 63.9% of diabetics met the recommended levels of HDL-C (>40 mg/dl in men and >50 mg/dl in women) in the 2005-2006, and 2007-2008 surveys, respectively. However, the study used a complete-case approach to missing data-restricting analyses only to respondents who had complete data for all lipids. We pooled data from the NHANES 2007-2008 and 2009-2010 cycles and estimated the percent of T2D meeting the recommended levels of HDL-C. T2D was defined as self-reported diagnosis at age≥ 30 , without initiation of insulin therapy within 1 year of diagnosis. Missing data for the lipids were handled in 2 ways: “all-available” approach included all respondents with data for any individual lipid; and the complete-case approach. Percentage estimates accounted for the complex sampling design of NHANES, and were age-adjusted to the US 2000 Census population. From a total of 20,686 respondents, 1,248 were identified as T2D; 1,114 (89.3%) and 507 (40.6%) were included in the all-available and completecase analysis of HDL-C, respectively. T2D included in complete-case analyses had significantly (p<0.001) higher HDL-C (mean 50.1, SD 13.3), and lower TG (mean 143.2, SD 68.1) than those excluded (HDL mean 46.5, SD 14.2; TG mean 395.6, SD 442.6). When age-adjusted, 46.9% of T2D (95% CI 36.5%-57.2%) met the recommended levels of HDL-C using the all-available approach compared with 67.2% (95% CI 52.9-81.5%) using the complete-case approach. These results suggest a larger therapeutic concern than previously appreciated. The marked difference was mainly driven by exclusion of subjects with low HDL-C and high TG levels in the complete-case analysis. The assumption of data missing at random can substantially impact results and must be carefully examined. ALBERTO MORABITO, CLAUDIA MERLOTTI, ANTONIO E. PONTIROLI, Milan, Italy ADA-Funded Research & Different intervention strategies can prevent new cases of type 2 diabetes (T2DM). Aim of the present systematic review and meta-analysis was to evaluate the effectiveness of different strategies. Studies were grouped into 15 different strategies: 1: diet plus physical activity; 2: physical activity; 3-6: anti-diabetic drugs [glitazones, metformin, beta-cell stimulating drugs (sulphanylureas, glinides), alfa-glucosidase inhibitors]; 7-8: cardiovascular drugs (ACE-inhibitors*, ARB**, calcium-antagonists); 9-14 [diets, lipidaffecting drugs (orlistat, bezafibrate), vitamins, micronutrients, estrogens, alcole, coffee]; 15: bariatric surgery. Only controlled studies were included in the analysis, whether randomized or non-randomized, and whether intentional interventions or post-hoc analysis (groups 7 and 8). Appropriate methodology (PRISMA statement) was used. Seventy-one studies (490,813 subjects), published in english language as full papers, were analysed to identify predictors of new cases of T2DM, and were included in a metaanalysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95% confidence intervals (CIs). Body mass index was in the overweight range for 13 groups, obese or morbidly obese in groups 9 and 15. All nonsurgical strategies, except for beta-cell stimulating drugs, estrogens, and vitamins, were able to prevent T2DM, with different effectiveness from 0.37 (0.26,0.52) to 0.85 (0.77,0.93); Multiple comparisons were not possible, but bariatric surgery was the most effective strategy [0.16 (0.11,0.24)]. These data indicate that several, but not all strategies, prevent T2DM; bariatric surgery was the most effective measure, indicating it as an adequate strategy for morbidly obese subjects. *ACE = angiotensin converting enzyme; **ARB = angiotensin receptor blockers For author disclosure information, see page 829. Guided Audio Tour poster A409 POSTERS 1564-P Increased Cancer and Mortality in Patients With Type 2 Diabetes: A 10-Years Cohort Study in Shanghai, China Epidemiology/ Genetics EPIDEMIOLOGY—OTHER EPIDEMIOLOGY—OTHER 1568-P 1570-P Do Sex Steroid Levels Influence Response to Weight Loss Interventions in Postmenopausal Women in the Diabetes Prevention Program (DPP)? Prevalence and Correlates of Diabetes among South Asians: Results from the MASALA Study ALKA M. KANAYA, KIANG LIU, SWAPNA DAVE, SHWETA SRIVASTAVA, YASIN PATEL, FAREEHA QURESHI, NAMRATHA KANDULA, San Francisco, CA, Chicago, IL POSTERS Epidemiology/ Genetics CATHERINE KIM, ELIZABETH L. BARRETT-CONNOR, JOHN F. RANDOLPH, SHENGCHUN KONG, BIN NAN, KIEREN J. MATHER, SHERITA H. GOLDEN, FOR THE DIABETES PREVENTION PROGRAM, Ann Arbor, MI, San Diego, CA, Indianapolis, IN, Baltimore, MD South Asians (SA) are the second fastest growing ethnic group in the US with approximately 3 million residents. SA have disproportionately high type 2 diabetes prevalence, but few studies have assessed glucose tolerance and measured sociocultural behaviors. We conducted a population-based study of SA between ages 40-84 without known cardiovascular disease. We obtained demographic, lifestyle and cultural information, conducted fasting and 2-hour glucose tolerance tests, physical examination, carotid ultrasound for intima media thickness and cardiac CT scan for coronary artery calcium (CAC). We created separate logistic regression models to examine covariates associated with prediabetes (fasting glucose 100-125 mg/dl and/or 2-hour post-challenge glucose 140-199 mg/dl) and diabetes (fasting glucose ≥126 mg/dl, 2-hour glucose ≥200 mg/dl and/or diabetes medication use). Of 810 (42% women) SA, mean age was 55±9, and 98% were immigrants living a median 27±11 years in the US. Mean BMI was 26±4 kg/m2; the prevalence of pre-diabetes was 30% and diabetes was 25%. The table shows covariates associated with each glycemic state. Similar metabolic covariates were associated with both pre-diabetes and diabetes among South Asians. A cultural variable, frequency of fasting, was associated with increased odds of pre-diabetes. Prospective follow-up of this cohort will determine whether fasting is predictive of incident diabetes as this may be a potentially modifiable risk factor. Prior studies have suggested that estrogen therapy leads to weight reductions in postmenopausal women. We examined whether estrogen use potentiates weight loss interventions via sex steroid levels and whether endogenous sex steroid levels predict response to weight loss interventions among women who do not use estrogen. The DPP was a randomized trial of the impact of an intensive life-style intervention (ILS) or metformin upon diabetes incidence in glucose intolerant adults. This secondary analysis examines postmenopausal women who did (n=324) or did not (n=382) use oral estrogen at baseline and 1 year. Main outcome measures were associations between baseline sex hormones and changes in weight and waist circumference (WC) by study arm. β-coefficients (sβ) were standardized by 1 standard deviation for each hormone. Among women not using estrogen, only higher baseline E2 was associated with weight loss only in the metformin arm, but not the ILS arm, even after adjustment for baseline weight, age, and race/ethnicity (sβ =-2.1, p=0.01). Among estrogen users, lower DHEA, but not E2, was associated with greater weight loss among women in the ILS arm, but not the metformin arm, even after adjustment for baseline weight, but this association was weakened after adjustment for age and race/ethnicity (sβ 1.0, p=0.06). Sex steroid levels were not associated with reductions in WC among estrogen users or non-users in the ILS or metformin arms. Among postmenopausal glucose-intolerant women who used estrogen, baseline sex steroid levels were not associated with response to weightloss interventions, suggesting that exogenous estrogen does not potentiate weight loss interventions by altering actual serum levels. In contrast, among women who did not use estrogen, higher baseline E2 levels were associated with greater weight loss among metformin users. Pre-diabetes model OR (95% CI) Age, per year 1.02 (1.00 – 1.05) Sex, reference group: male 0.76 (0.49 – 1.18) Family history of DM 1.61 (1.09 – 2.37) Hypertension (≥140/90 mmHg or medication use) 1.61 (1.04 – 2.48) Waist circumference, per cm 1.03 (1.01 – 1.06) Total cholesterol, per mg/dl — HDL cholesterol, per mg/dl — Triglycerides, per mg/dl 1.01 (1.00 – 1.01) Ln (CAC + 1) 1.14 (1.03 – 1.27) Fasting practice, reference: never fasts Fasts 1-3 times/week 1.76 (0.95 – 3.28) Fasts 1-2 times/month 0.40 (0.17 – 0.92) Fasts < once per month 0.84 (0.42 – 1.69) Fasts approximately once per year 0.89 (0.54 – 1.46) Supported by: U01DK048489; R01DK083297; K23DK071552 1569-P WITHDRAWN Diabetes model OR (95% CI) 1.03 (1.00 - 1.06) 1.02 (0.60 - 1.74) 3.15 (1.96 – 5.07) 3.54 (2.10 – 5.97) 1.04 (1.01 - 1.07) 1.04 (1.02 – 1.07) 0.95 (0.93 – 0.97) — 1.19 (1.06 – 1.32) — Supported by: NIH/NHLBI (5R01HL093009) 1571-P Lower Blood Volume in the Pulmonary Vasculature Is Associated With Diabetes GREGORY L. KINNEY, JENNIFER BLACK-SHINN, SHARON LUTZ, RAUL SAN JOSÉ ESTÉPAR, GEORGE WASHKO, JOHN E. HOKANSON, Aurora, CO, Boston, MA Diabetes damages organ systems primarily through increased inflammation and disrupted glycemic control. The effects of diabetes on the lung have been of interest for decades but the modest reduction in pulmonary function and its non-progressive nature have limited investigation into its cause. One of the primary candidates is reduction in diffusing capacity due to reduced pulmonary capillary blood volume. This study reports the results of CT measurement of pulmonary blood volume comparing individuals with and without diabetes. One hundred four smokers with at least 10 pack years smoking history and no obstructive lung disease were recruited from the COPDGene study, mean age 57 ± 10. Ten participants reported diabetes and 94 did not. None of the participants without diabetes reported use of insulin or insulin sensitizing agents. Intraparenchymal pulmonary vessels were automatically segmented and measured from a CT scan of the chest. Total Blood Vessel Volume (TBV) and the aggregate vessel volume (BV) for all vessels was calculated in increments of 5mm2 cross section area (CSA) ranging from ≤ 5mm2 through 90mm2. BV at each increment was divided by TBV and expressed as % TBV and these values were compared by diabetes status. P values were calculated at each increment using Mann-Whitney U. Participants with diabetes were older, reported more pack years of smoking, and did not differ by sex or BMI. They showed reduced pulmonary function (FEV1 2.5 vs 3.01, p=0.002 and FVC 3.2 vs 3.9, p=0.001) but no & For author disclosure information, see page 829. A410 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—OTHER NNT of 77 (to eliminate one MACE event over 10 years). The results provide support that the current ADA standard for SBP treatment in the general population with T2D would result in significantly lower rates of major CV events at clinically relevant levels of NNT. Large scale prospective clinical trials would be required to confirm these findings. difference in bronchodilator response, total lung capacity or % emphysema. BV in the smallest vessels (≤5mm2 CSA) was significantly reduced in participants with diabetes (53% vs 57% p=0.02) and increased in all vessels > 40mm2 where 4 of 10 comparisons were significant at p <0.05. To our knowledge this is the first study to show reduced pulmonary blood volume in vessels < 5mm2 (CSA) with concomitant echo of volume in the largest vessels. Reduced blood volume may play an important role in the reduced pulmonary function seen in diabetes. 1574-P Diabetes, Diabetes Risk Factors and Treatments, and Breast Cancer Supported by: U01HL089856, U01HL089897 To clarify the potential association between diabetes, related factors, treatments and breast cancer risk, a series of meta-analyses was carried out following PRISMA guidelines. For breast cancer at all ages, the risks obtained from prospective studies were: diabetes (SRR=1.27, 95% CI (1.16, 1.39); physical activity (SRR=0.88 (0.85,0.92)); glycaemic load (SRR=1.05, (1.00, 1.10)); glycaemic index (SRR=1.05,(1.00, 1.09)); fasting glucose (SRR=1.14, (0.94, 1.37)); serum insulin(SRR=1.11, (0.75, 1.85)); c-peptide (SRR=1.00, (0.69, 1.46)) and adiponectin (SRR=1.16, (0.93, 1.46. An increase of 5 units in BMI was associated with post-menopausal breast cancer (SRR=1.12, 95% CI (1.08, 1.16)) but not at pre-menopausal ages (SRR=0.83, 95% CI (0.72, 0.95)). Serum insulin and c-peptide were associated with breast cancer at post-menopausal ages but not at pre-menopausal. For IGF-1, Hodge’s Standardised Mean Difference (HSMD) was calculated and there was no significant association with breast cancer (HSMD=0.026, 95% CI (-0.031, 0.084). The SRR for breast cancer among users of insulin glargine was 1.08 (0.98, 1.20) and was 0.92 (0.32, 2.65) when restricted to randomized trials. Among new users, the SRR for breast cancer was 1.09 (0.98, 1.21) and there was no trend of increasing breast cancer risk with increasing duration of use of glargine (β=0.04)(p=0.52). Risk of breast cancer in a prospective cohort declined with increasing follow-up, from 1.99 (1.31, 2.03) with two years of follow-up, to 1.60 (1.10, 2.32) with 3 years, 1.50 (1.10, 2.10) with four years and 1.18 (0.84, 1.66) with five years of follow-up. There is no reduction in risk of breast cancer associated with metformin use (SRR=0.96, 95% CI (0.85, 1.08)) even for the longest duration of use (SRR=0.94, 95% CI (0.81, 1.09)). An association between these two common diseases could have important implications for public health with common risk factors driving further increases in both diseases yet holding the tantalizing possibility for prevention of both. KIMBERLY G. BRODOVICZ, ZHIWEN LIU, SAMUEL S. ENGEL, CHARLES M. ALEXANDER, CYNTHIA J. GIRMAN, North Wales, PA, Rahway, NJ Psoriasis affects 1-4% of the adult population and patients with psoriasis are 20-40% more likely to develop type 2 diabetes (T2DM) than patients without psoriasis. This study in 3 administrative databases examined the prevalence of psoriasis in patients with T2DM and without diabetes. Psoriasis prevalence was estimated using an electronic medical records database from the UK (Clinical Practice Research Datalink, CPRD, Jan 2003-Oct 2011) and 2 US insurance claims databases (Clinformatics DataMart, OptumInsight™, Jan 2003-Dec 2011 and Humana Medicare Advantage Plan, Jan 2007Jan 2011). CPRD data included patients aged ≥25 yrs; OptumInsight data included patients aged 25-64 yrs; Humana data included patients aged ≥65 yrs. Patients with ≥12 months of continuous enrollment were included. The index date was the date of first record in the study period of a T2DM defining event (diagnosis code, antihyperglycemic prescription, or laboratory result) or, for patients without diabetes, the date of the first record in the study period meeting entry criteria. Psoriasis (by diagnosis code) prevalence in the year before the index date was estimated. Roughly 1% of the population in each database had a psoriasis diagnosis (table). Across all 3 databases, the proportion of patients with T2DM and a psoriasis diagnosis was twice that of patients without diabetes, with 1.3-2.7% of patients with T2DM having a psoriasis diagnosis (table). The apparently increased prevalence of psoriasis in T2DM warrants further investigation. Total Population with psoriasis Patients with T2DM with psoriasis Patients without diabetes with psoriasis CPRD 4,779,111 63,812 (1.3%) 285,542 7,724 (2.7%) 4,493,569 56,088 (1.2%) OptumInsight Humana MAPD 4,300,715 1,736,442 46,486 (1.1%) 15,967 (0.9%) 1,406,104 586,483 22,280 (1.6%) 7,456 (1.3%) 2,894,611 1,149,959 24,206 (0.8%) 8,511 (0.7%) 1575-P Factors Associated With Untreated Diabetes: The Japanese National Health and Nutrition Survey MAKI GOTO, ATSUSHI GOTO, NAYU IKEDA, HIROYUKI NODA, KENJI SHIBUYA, MITSUHIKO NODA, Tokyo, Japan, Osaka, Japan 1573-P Clinical Implications of Changing ADA Guidelines for Systolic Blood Pressure (SBP) Management: A Modeling Analysis Currently, a large number of individuals with diabetes do not receive treatment in Japan. We used data from the Japanese National Health and Nutrition Survey, 2005-2009, to examine factors associated with untreated diabetes. Excluding individuals aged less than 20 years and pregnant women, 40,431 participants were included in the analysis. Diabetes was defined as a diagnosis of diabetes, HbA1c (NGSP) ≥ 6.5%, fasting plasma glucose ≥126 mg/dL, or casual glucose ≥ 200 mg/dL. Diabetic participants (n = 5,043) tended to have a higher age and body mass index (BMI) (kg/m2) than non-diabetic participants; 2,245 were currently being treated for diabetes, whereas, 2,798 were not. The untreated participants had lower HbA1c than the treated participants (6.6% vs 7.3%; P < 0.001). However, in a subgroup analysis restricted to participants with higher HbA1c (≥ 7.0%), untreated participants had higher HbA1c than the treated participants (8.6% vs 8.1%; P < 0.001). We also conducted multiple logistic regression analysis to examine factors associated with untreated diabetes among diabetic participants. We included covariates such as sex, age (year), BMI, exercise habits (yes/no), and smoking history (never, past, or current). We found that age (odds ratio = 0.97 [95% confidence interval = 0.96-0.97]), BMI (0.96 [0.95-0.98]), and exercise habits (0.76 [0.65-0.87]) were inversely associated with untreated diabetes. Additionally, in a subgroup analysis restricted to higher HbA1c, sex (male vs female; 1.34 [1.01-1.79]), age (0.96 [0.95-0.97]), and exercise habits (0.77 [0.60-0.97]) were associated with untreated diabetes. In conclusion, our findings indicate that many untreated diabetic participants had poor glycemic control; further, younger age, male gender, lower BMI, and physical inactivity may be factors related to untreated diabetes. Promoting an environment that leads individuals to consult a doctor may be important especially among younger, lean, or physically inactive population. BETH D. MITCHELL, SARAH WARD, BRAD CURTIS, DAVID R. NELSON, DAVID M. KENDALL, Indianapolis, IN The ADA has provided guidelines recommending a SBP goal of <130 (all values mmHg) as appropriate for the majority of patients with type 2 diabetes (T2D). This recommendation has been challenged as the ACCORD trial found that targeting SBP <120 in T2D patients at high risk for cardiovascular (CV) events provided no additional benefit in reducing CV risk although resulted in a significant reduction in the risk of stroke. The aim of this analysis was to compare the impact of lowering SBP levels from those observed in a community population with type 2 diabetes (NHANES with mean SBP of >140), as compared to achieving SBP targets of <120 or <130 on rates of major CV events. In order to provide a broader perspective than that derived from the ACCORD trial, we utilized the Archimedes Model to simulate 10,000 virtual patients, performed to estimate rates of major adverse coronary events (MACE), myocardial infarction (MI), and stroke. Output from each simulation included the number of CV events (95% CI) for individuals receiving (1) current care of SBP as observed in NHANES (mean SBP of 151) (2) achieving SBP targets of <130 or (3) achieving SBP targets of <120. The simulated population (45% male) had a mean age of 61.0 yrs, and baseline HbA1c of 7.5 %. As compared to the current SBP achieved in the NHANES population, lowering mean SBP to < 130 in all patients would result in an additional 24% relative risk reduction (RRR) in MACE, while lowering to < 120 achieved a 30% RRR. Therefore a strategy aimed at reducing SBP to <130 would require a number needed to treat (NNT) of 21 (to eliminate 1 MACE event over 10 years), while further lowering SBP from <130 to <120 results in ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A411 POSTERS 1572-P Prevalence of Psoriasis in Patients With Type 2 Diabetes Epidemiology/ Genetics PETER BOYLE, ALICE KOECHLIN, CHRIS ROBERTSON, MARIA BOTA, MATHIEU BONIOL, DEREK LEROITH, GEREMIA B. BOLLI, JULIO ROSENSTOCK, PHILIPPE AUTIER, Lyon, France, Glasgow, United Kingdom, New York, NY, Perugia, Italy, Dallas, TX EPIDEMIOLOGY—OTHER the presence of HP infection worsened glycemic control in patients with diabetes. 1576-P Factors Influencing Time to Case Ascertainment in Youth With Type 1 (T1D) and Type 2 Diabetes (T2D) in the SEARCH for Diabetes in Youth Study TESSA L. CRUME, RICHARD F. HAMMAN, SCOTT ISOM, JASMIN DIVERS, ELIZABETH MAYER-DAVIS, WENZE ZHONG, SHARON H. SAYDAH, DEBRA A. STANDIFORD, JEAN M. LAWRENCE, CATHERINE PIHOKER, DANA DABELAA, Aurora, CO, Winston-Salem, NC, Chapel Hill, NC, Atlanta, GA, Cincinnati, OH, Pasadena, CA, Seattle, WA 1578-P The Association of Leg Length With Metabolic Abnormalities Underlying Type 2 Diabetes Mellitus: The PROMISE Cohort LUKE W. JOHNSTON, STEWART B. HARRIS, RAVI RETNAKARAN, HERTZEL C. GERSTEIN, JILL K. HAMILTON, BERNARD ZINMAN, ANTHONY J. HANLEY, Toronto, ON, Canada, London, ON, Canada, Hamilton, ON, Canada Although shorter leg length (LL), a marker of early childhood deprivation, has been linked with increased risk of type 2 diabetes mellitus (DM), there is limited data regarding LL and the metabolic change underlying DM. Our aim was to study the association of LL with insulin resistance (IR) and β-cell dysfunction. Height and sitting height were measured on 524 non-diabetic subjects in the PROMISE cohort to calculate LL and leg-to-height ratio (LHR). Glucose and insulin were measured during an oral glucose tolerance test. IR was assessed using HOMA-IR and the Matsuda insulin sensitivity index (ISI). The insulinogenic index over HOMA-IR (IGI/IR) and the Insulin Secretion Sensitivity Index 2 (ISSI-2) was used to evaluate β-cell function. Linear regression models were adjusted for age, sex, ethnicity, family history of diabetes, waist, and weight. LL and LHR were significantly associated with HOMA-IR (β = -0.03 (SE 0.007), β = -8.97 (2.01), respectively) and ISI (β = 0.027 (0.007), β = 6.77 (2.02), respectively, all p < 0.001) after full adjustment. LHR was significantly associated with ISSI-2 (β = 2.87 (1.3), p = 0.027), but not with IGI/IR (β = 5.95 (3.1), p = 0.056). Interaction analyses indicated that increased LL significantly modified the detrimental effect of higher waist size on IR (p < 0.009; Figure). Shorter legs were associated with greater IR and β-cell dysfunction, suggesting that early childhood deprivation may increase the risk of developing DM. POSTERS Epidemiology/ Genetics A sustainable diabetes surveillance system for U.S. youth (age 0-19 years) requires us to better understand case ascertainment. Using the SEARCH for Diabetes in Youth registry, we examined the relationship between time from diabetes diagnosis to case identification/registration and how it differed by diabetes type (T1D, T2D), demographics (age and race/ethnicity) and type of diabetes provider. We included all 2002-2007 incident cases of T1D (n=6181) and T2D (n=1611) among youth aged 0-19 years registered by the SEARCH study. Plots for time from diagnosis to registration were developed and differences by core variables were examined using the Wilcoxon test. We found that it took 2.5 times longer to identify the median number of total registered T2D cases compared to T1D cases at similar levels of ascertainment (Figure) (p<0.001). For T1D, a longer time to registration was associated with older age (15-19 years vs. younger) (p<0.001) and having a primary diabetes care provider other than an endocrinologist (p<0.001). For T2D, only having a primary diabetes care provider other than an endocrinologist was associated with a longer time to case ascertainment (p<0.0001). These patterns likely reflect US health care delivery’s decentralized nature, the need to identify multiple providers and hospitals for nearly complete ascertainment, and use of more specialized care by youth with T1D than those with T2D. Supported by: CDC 1577-P Effect of Helicobacter Pylori (HP) Infection on Glycemic Control in Patients With Diabetes: A Meta-Analysis SAKIKO YOSHIZAWA, SATORU KODAMA, RYOKO TAJIMA, KAZUYA FUJIHARA, CHIKA HORIKAWA, YOKO YACHI, AKIKO SUZUKI, OSAMU HANYU, HITOSHI SHIMANO, HIROHITO SONE, Niigata, Japan, Mito, Japan, Tokyo, Japan, Tsukuba, Japan It has been hypothesized in several studies that HP infection worsens glycemic control in patients with diabetes based on the general finding that chronic infection causes persistent hyperglycemia. However, results of studies to prove or disprove that hypothesis have been inconsistent. The aim of this meta-analysis was to compare glycemic control between diabetic patients with and without HP infection. We searched for studies reporting the hemoglobin A1c (A1C) level according to the existence of HP infection using Biosis, MEDLINE, Embase, PASCAL, and SciSearch. Mean difference in A1C between diabetic patients with and without HP infection was pooled with a random-effects model. We analyzed 13 eligible studies. The Figure is a forest plot of mean differences in A1C in those with HP infection vs. those with HP non-infection with 95% confidence intervals (CIs). Overall, compared with diabetic patients without HP, those with HP did not have significantly higher A1C levels (mean difference [95% CI], 0.2% [-0.1-0.5]) (Figure). In the 11 studies that specified the type of diabetes, there were modest differences in A1C between patients with and without HP (mean difference [95% CI]: 0.7% [-0.3-1.7] for type 1 diabetes (5 studies); 0.3% [0.00.6] for type 2 diabetes). In conclusion, there was insufficient evidence that & For author disclosure information, see page 829. A412 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—OTHER 1579-P 1581-P Recent Trends in Breastfeeding Initiation Rates among Women With and Without Diabetes during Pregnancy, 2006-2011 Smoking Cessation in Relation to Weight, Glycemic Control, Blood Pressure, and Lipid Levels in Patients With Type 2 Diabetes: The Japan Diabetes Outcome Intervention Trial-2-LT Study REENA OZA-FRANK, Columbus, OH National data indicate recent increases in rates of breastfeeding initiation. Whether these increases are consistent among women with diabetes, who have been shown to have lower rates, is unknown. Ohio birth certificate data from 2006-2011 were used to determine trends in breastfeeding at discharge by diabetes status (no diabetes [NDM], gestational diabetes mellitus [GDM], or prepregnancy diabetes mellitus [PDM]). Logistic models were built, using year as an ordinal variable and adjusting for mother’s sociodemographic and relevant clinical variables, to determine significant trends over time. Among 807,466 births in Ohio from 2006-2011, 5.5% of women had GDM and 0.8% had PDM. Rates of breastfeeding increased among NDM and PDM, however, rates among PDM were consistently lower than NDM or GDM (Table). Despite similar rates to NDM prior to 2011, rates among GDM increased through 2010 and declined in 2011 to a rate lower than NDM or PDM. Contrary to previous literature, GDM women had breastfeeding rates as high as or even higher than NDM women in most years, whereas PDM rates were the lowest. Future studies on breastfeeding should differentiate between GDM and PDM. Despite increases in Ohio breastfeeding rates in some subgroups, rates were lower than the national average (77%) and Healthy People 2020 goals (82%). Additional efforts to increase breastfeeding initiation rates in Ohio, especially among women with PDM, are necessary to meet national goals. Table. Trends in Breastfeeding at Discharge by Diabetes Status, Ohio 20062011 2006 2007 2008 2009 2010 2011 No diabetes** 62.5 63.1 64.2 65.0 67.2 69.1 Gestational diabetes** 63.0 64.0 65.3 65.7 67.4 61.1 Prepregnancy diabetes* 60.0 59.3 60.2 58.2 64.5 62.3 P for trend: *p<0.001; **p<0.0001 1582-P 1580-P Assessing the Phenotypic Extremes of Type 2 Diabetes in the UK Biobank Study of 500,000 Individual Status of Diabetes-Related Preventive Care Practices among U.S. Adult Caregivers With Diabetes, 2009 JESSICA S. TYRRELL, MICHAEL N. WEEDON, TIMOTHY M. FRAYLING, Truro, United Kingdom, Exeter, United Kingdom PYONE CHO, LINDA S. GEISS, ISRAEL HORA, Atlanta, GA Managing one’s own diabetes and living well with the disease is difficult. However, the growing prevalence of diabetes in middle-aged and older adults means that many people with diabetes have to take care of a loved one with poor health, potentially disturbing their own preventive care routines. To determine the impact of caregiving on diabetes management, we analyzed responses from the 2009 Behavioral Risk Factor Surveillance system diabetes module and assessed the status of preventive care practices (annual doctor’s visit, A1C testing, dilated eye exam, foot exam, flu and pneumococcal vaccination; daily blood sugar testing, foot self-exam, blood pressure medication adherence, and aspirin medication compliance) among adult respondents aged ≥ 18 years with diabetes and who provided informal care to others. Of 39,167 adult respondents with diabetes, 17% were aged ≥ 65 years; 49% were female; 89% had health insurance at the time of the survey; 19% reported very good or excellent health; 67% were hypertensive; 55% had attended a diabetes self-management class; and 25% served as informal caregivers. There was no significant difference between persons with diabetes who had caregiver responsibility and those who did not for several routine preventive care practices−annual doctor’s visit (87%), A1C testing (70%), dilated eye exam (71%), foot exam (72%), flu(61%) and pneumococcal vaccination (53%); daily blood sugar testing (61%), foot selfexam (73%), and blood pressure medication adherence (90%). While both caregivers and non-caregivers with diabetes complied poorly with a daily aspirin regimen (54% and 58%), the caregivers were more likely to have had diabetes self-management education compared to the non-caregivers (59% vs. 54%, p<0.0005). Although adults with diabetes generally followed similar levels of preventive care practices regardless of their caregiver status, the level of compliance with many care practices could be improved for both groups. ADA-Funded Research & The UK Biobank study includes 500,000 individuals aged between 40 and 69 years of whom 26,412 had diabetes at baseline. We aimed to identify and assess diabetes family history in type 2 diabetic and unaffected individuals at very low and very high risk of the condition based on BMI, age and sex. Genome-wide or exome-wide sequencing of these individuals is likely to provide improved power to detect low frequency risk or protective alleles associated with diabetes compared to the same number of randomly selected cases and controls. We used 14,362 individuals defined as having type 2 diabetes (age at diagnosis >35 years and no insulin within one year of diagnosis) and 446,892 unaffected individuals of British ancestry. We calculated a liability score for each individual using residuals from a logistic regression model with BMI, age and sex as risk factors and type 2 diabetes as an outcome. We identified 4860 affected individuals at low risk compared to 29 expected by chance at >4 standard deviations (SDs) from the liability score mean (p<0.0001). In contrast there were only two unaffected individuals at high risk (>4SDs) compared to the 29 expected by chance. Comparing the 1000 unaffected individuals at most risk with the 1000 unaffected individuals at least risk, there was no difference in parental history of diabetes (18.9% vs. 17.1%, p=0.40). Comparing the 1000 affected individuals at least risk to the 1000 affected individuals at most risk, the low-risk individuals were much more likely to have a parental history of diabetes (47.9% vs 31.8% p<0.0001). In summary, using data from 461,254 UK Biobank individuals, a type 2 diabetes liability score identifies an excess of affected individuals at low risk of the disease with a strong family history of the disease but no excess of protected unaffected individuals at high risk. Supported by: Diabetes UK For author disclosure information, see page 829. Guided Audio Tour poster A413 POSTERS Earlier studies have associated cigarette smoking with a high risk of type 2 diabetes (T2D). Further, smoking cessation has been associated with a high risk of T2D, possibly mediated by weight gain. However, the associations of smoking cessation with longitudinal changes in weight, glycemic control, blood pressure (BP), and lipid levels in patients with T2D remain unclear. To investigate the associations, we conducted an observational study in the cluster-randomized controlled trial that examined the effect of a coordinated intervention on patients’ adherence to regular visits over a 1-year period in Japanese patients with T2D. Of the 2,200 participants, 1,169 responded to the smoking questionnaire at both baseline and end of follow-up. Excluding 10 new smokers, we classified 1,159 patients into 3 groups: continuing smokers (n = 328), quitters (n = 42), and non-smokers (n = 789). To examine the associations, we used the mixed-effects model adjusting for age, sex, intervention arm, and baseline weight, physical activity, the Problem Areas in Diabetes scale, and hypoglycemic medication use. Compared with continuing smokers, quitters had similar changes in weight (difference in mean changes per month, 0.00 kg; 95% confidence interval [CI], -0.03-0.04; P = 0.61) and levels of HbA1c (0.00 %; 95% CI, -0.00-0.02; P = 0.11), LDL (-0.15 mg/dl; 95% CI, -0.57-0.27; P = 0.48), non-HDL (0.03mg/dl; 95% CI, -0.40-0.46; P = 0.91), and total cholesterol (0.04 mg/dl; 95% CI, -0.46-0.54; P = 0.87). However, quitters, compared with continuing smokers, showed greater elevations in systolic BP (0.36 mmHg; 95% CI, 0.08-0.65; P = 0.01) and diastolic BP (0.27 mmHg; 95% CI, 0.04-0.50; P = 0.02). Thus, we conclude that although smoking cessation may not be associated with weight gain, worsening of glycemic control, or elevations in lipid levels over a 1-year period in patients with T2D, it may be associated with modest elevations in BP. Epidemiology/ Genetics ATSUSHI GOTO, YASUAKI HAYASHINO, KAZUO IZUMI, SHINU HAYASHI, HIKARI SUZUKI, KATSUYA YAMAZAKI, MITSUHIKO NODA, Tokyo, Japan, Nara, Japan, Toyama, Japan, Ibaraki, Japan EPIDEMIOLOGY—OTHER 1583-P 1585-P A Sibling Analysis of the Relationship between Diabetes during Pregnancy and Fetal Growth Sleep Duration and Glycemic Control in Patients With Diabetes Mellitus: Korea National Health and Nutrition Examination Survey 2007-2010 KELLY J. HUNT, JEFFREY E. KORTE, MULUGETA GEBREGZIABHER, JILL MAULDIN, MARIA E. MAYORGA, Charleston, SC, Clemson, SC BU KYUNG KIM, JA YOUNG JEON, SO-YEON AN, MIN SUK LEE, YONG JUN CHOI, SEUNG JIN HAN, YOON-SOK CHUNG, KWAN-WOO LEE, DAE JUNG KIM, Busan, Republic of Korea, Suwon, Republic of Korea Short sleep duration has been reported to increase the risk of diabetes. However, the influence of sleep duration on glycemic control in diabetic patients has not been clarified. In the present study we evaluated the association between sleep duration and glycemic control in diabetic patients. We analyzed the data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2010. Sleep duration was self-reported, and classified into five groups: <6, 6, 7, 8, and ≥9 h/day. Continuous and categorical variables were compared among the five groups using ANOVA and the χ2 test. To control for socioeconomic and lifestyle factors and comorbidities, logistic regression was used. The results of fasting blood glucose and HbA1c according to sleep duration showed a U-shaped trend, which was stronger in females and younger patients (<65 years). The patients with a sleep duration of 7 h/day had the lowest HbA1c (7.26%) among the subjects (p=0.026). If the sleep duration was shorter or longer than 7 h/day, the HbA1c level was elevated. In the older age group (≥65 years), a sleep duration of 6 h/day was associated with the lowest HbA1c (7.26%). The adjusted odds ratio (OR) with a 95% confidence interval (CI) associated with the sleep duration of ≥9 h/day (vs. 7 h/day) was 1.47 (1.03-2.10) for HbA1c. Our results suggest that sleep duration is associated with glycemic control in diabetic patients. The adequate sleep duration in Korean adults with diabetes was approximately 7 h/day, and could be shorter for older patients. POSTERS Epidemiology/ Genetics We conducted a sibling analysis to examine the relationship between diabetes during pregnancy and fetal growth. Using linked birth certificate, inpatient hospital and prenatal claims data we examined black and white women with more than one singleton birth delivered at 34-44 weeks gestation in South Carolina between 2004 and 2008. Among 29,722 women with 61,789 infants, 2,203 women had 4,600 infants discordant for in utero diabetes exposure. We used both conventional generalized estimating equations (GEE), and fixed-effects models which account for measured and unmeasured shared familial factors. Results from the GEE analysis in the 61,789 infants indicate that prepregnancy and gestational diabetes are associated with increased birthweight in both whites and blacks. In contrast, results from the fixed-effects model indicate that in whites and blacks neither prepregnancy nor gestational diabetes are significantly associated with increased birthweight when shared familial factors are accounted for. When analyses are limited to women with infants discordant for in utero diabetes exposure, results are attenuated in the GEE model and remain non-significant in the fixed effects model. Shared family characteristics (genetic, environmental) appear to explain differences in birthweight among siblings with discordant in utero diabetes exposure. Hence, between rather than within family differences may account for the increased fetal growth associated with diabetes. 1586-P Global Burden of Diabetes in Women of Childbearing Age: A Review of Prevalence Estimates ADOLFO CORREA, JESSICA MARCINKEVAGE, CSABA SIFFEL, PIERPAOLO MASTROIACOVO, LORENZO BOTTO, Jackson, MS, Atlanta, GA, Rome, Italy, Salt Lake City, UT Diabetes in pregnancy is one of the most common pregnancy complications, yet data on the burden of diabetes among women of childbearing age are limited. To estimate the prevalence of diabetes in women of childbearing age by global region, we conducted a review of studies with prevalence data on diabetes in women of childbearing age (15-49) published from 2000 to 2011. We derived prevalence estimates for each type of diabetes (i.e., diabetes=type 1 or type 2; GDM= gestational diabetes) by country, region, and development status as defined by the United Nations (UN). We identified 295 studies with information on diabetes prevalence in women of childbearing age, representing 65 countries (41 less developed, 24 more developed). Diagnostic criteria for both diabetes and GDM varied greatly across studies. For diabetes, the median global prevalence was 3.35%; of those developed countries with diabetes data (n=15), only 27% of estimates were above the median, while over half of estimates from less developed countries with diabetes data (n=34) were above the median. For GDM population data, we found a median global prevalence of 3.89%, with only 38% of developed countries with GDM population data (n=13) above the median while 64% of less developed countries with GDM population data (n=11) were above the median. When applied to UN population estimates for women aged 15-49, the median prevalence for diabetes corresponds to ~58 million women, of whom >50 million live in less developed countries. The median estimate for GDM prevalence corresponds to ~11 million women, of whom 10 million live in less developed countries. This review suggests a significant number of women of childbearing age are affected by diabetes worldwide, particularly in less developed countries, highlighting the need for targeting this group in: a) efforts to conduct diabetes surveillance using standard diagnostic criteria, and b) examination of current national policies and interventions for diabetes prevention and proper diabetes control. Supported by: National Institute on Minority Health and Health Disparities (R01MD004251) 1584-P WITHDRAWN & For author disclosure information, see page 829. A414 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—OTHER 1587-P 1589-P Socioeconomic Position and Sensory Impairment Among U.S. Working-Age Adults With Diabetes Treatment Utilization Patterns of GLP-1 Agonists and DPP-4 Inhibitors among Type 2 Diabetics in a U.S. Commercially Insured Population: 2005–2011 CHIU-FANG CHOU, GLORIA L.A. BECKLES, YILING J. CHENG, JINAN B. SAADDINE, Decatur, GA, Atlanta, GA CAROL E. KORO, PANKDEEP CHHABRA, MONIKA STENDER, C. VICTOR SPAIN, JEFFERY K. ALLEN, HENRY J. KRZYWY, Collegeville, PA, Baltimore, MD, Stockley Park, United Kingdom, Philadelphia, PA, Research Triangle Park, NC Socioeconomic position (SEP) is associated with diabetes (DM) and sensory impairment (SI) among adults. DM, a major cause of SI, has increased among U.S. adults. Yet, the effect of SEP on SI among working-age adults with DM has not been studied. We examined the relationship between SEP and SI among adults aged 25-64 years with DM using 2007-2011 National Health Interview Surveys (N=7,164). SI was defined by self-reports of visual (VI) or hearing impairment (HI). SEP indicators were occupation (white-collar (highest SEP), service group, farm worker, blue-collar, not in labor force), education (<high school, high school, some college, ≥college), and poverty-income-ratio (<1.00-poor, 1.00-2.99-low, 3.00-3.99-middle, ≥4.00-high income). We conducted logistic regressions to estimate adjusted prevalence ratios (APRs) for the association between each SEP indicator and VI and HI, controlling for age, gender, race/ ethnicity, nativity, marital status, insurance coverage, usual source of care, annual eye doctor visits , smoking, other DM complications, DM medication, and time since DM diagnosis. We used SAS callable -SUDAAN to account for the complex survey design. Differences were significant at p<0.05. Nearly 36% of U.S. working-age adults with DM had SI. Compared with the highest SEP level for each indicator, APRs for VI were significantly higher for people with some college (1.2, 95% CI=0.7-2.2), high school (1.3, 95% CI=0.7-2.2), or <high school (1.5, 95% CI=0.8-2.5) education; for blue-collar workers (1.2, 95% CI=0.7-2.0); and for those in poor (1.5, 95% CI=0.9-2.5), low income (1.4, 95% CI=0.8-2.4), or middle income (1.2, 95% CI=0.7-2.1) families. For HI, APRs were also significantly higher for people with some college or <high school; farmers, blue-collar workers; and people in poor families. SEP was independently associated with SI among working-age adults with DM. Interventions are needed to target adults with DM in low SEP to increase the effectiveness of risk-reduction efforts. 1588-P MPR for refill adherence < 80% >= 80% Ethnic Disparities in Conversion from Impaired Fasting Plasma Glucose to Type 2 Diabetes WANDA ADMIRAAL, FRITS HOLLEMAN, MARIEKE SNIJDER, RON PETERS, LIZZY BREWSTER, JOOST HOEKSTRA, KARIEN STRONKS, IRENE VAN VALKENGOED, Amsterdam, Netherlands Type of Index ADA Add-on therapy Despite the ethnic differences in prevalence and incidence of type 2 diabetes (DM), evidence on ethnic disparities in conversion rate from prediabetes to DM is scarce. We aimed to compare the association of impaired fasting glucose (IFG), as well as fasting plasma glucose (FPG), with the 10-year cumulative incidence of DM between South Asians, Africans and Caucasians. We analysed data on 90 South Asians, 190 Africans and 176 Caucasians, who had participated in the population based SUNSET study between 20012003 and participated in a follow up visit between 2011-2012. We excluded those with a missing FPG at baseline, a missing FPG at follow up, or with DM at baseline. Baseline IFG was defined as an FPG of 5.7 mmol/L - 6.9 mmol/L. At follow up, DM was defined as an FPG ≥ 7.0 mmol/L, HbA1c ≥ 48 mmol/mol (6.5%) or self reported DM. Of all participants 41.2% were men and the mean age at baseline was 45.6 ± 6.4. The 10-year cumulative incidence of DM was 18.9% in South Asians, 13.7% in Africans and 4.5% in Caucasians (p<0.05). We found a much stronger association of both IFG and FPG with the 10-year cumulative incidence of DM in the South Asians than in the Africans and Caucasians. The ethnic difference in association, particularly of FPG, remained statistically significant after adjustment for sex, age, baseline BMI and change in BMI over 10 years (FPG: odds ratio of 17.9 [3.7-67.8] in South Asians, 6.8 [2.617.8] in Africans, 1.9 [0.5-6.9] in Caucasians per mmol/L increase in FPG. IFG: odds ratio of 11.1 [3.0-40.8] in South Asians, 5.1 [2.0-13.3] in Africans and 2.2 [0.5-10.2] in Caucasians with IFG at baseline compared to those without IFG at baseline). We found a higher 10-year cumulative incidence of DM and a much stronger association of baseline IFG and FPG with DM among the South Asians and Africans than among the Caucasians. Our findings do not only emphasize the high risk of DM in South Asians, but also suggest a more rapid conversion from IFG to DM in South Asians and, to a lesser extent, those of African origin than in Caucasians. ADA-Funded Research & New Use therapy Switch therapy DPP4 inhibitors, n (%) GLP-1 agonists, n (%) Other ADA, n (%) GLP vs Other DPP4 ADAs, inhibitors vs overall chisq Other ADAs, p-values chisq p-values <.0001 <.0001 11,363 (5.45) 12,195 (9.76) 50,610 (4.26) 197,320 112,730 1,136,892 (94.55) (90.24) (95.74) 120,603 (57.79) 31,372 (15.03) 48,022 (23.01) Treatment Modification Discontinuation of 143,038 index ADA (68.54) Switching of index ADA 42,570 (20.40) Add-on therapy 37,800 (18.11) <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 92,892 49,737 (4.19) (74.36) 10,157 (8.13) 1,096,225 (92.31) 17,806 38,828 (3.27) (14.25) 101,509 (81.26) 44,333 (35.49) 13,780 (11.03) 927,050 (78.07) 191,532 (16.13) 151,923 (12.79) 1590-P Changes in County-Level Disparity in Diagnosed Diabetes Prevalence and Incidence in the Unites States, 2004-2009 SUNDAR S. SHRESTHA, THEODORE J. THOMPSON, KAREN A. KIRTLAND, EDWARD GREGG, GLORIA L. BECKLES, LAWRENCE E. BARKER, LINDA S. GEISS, Atlanta, GA County-level disparities in the prevalence/incidence of diabetes exist, but how these disparities have changed over time is unknown. We examined the change in county-level diagnosed diabetes prevalence/incidence among U.S. adults during 2004-2009. We fit unadjusted and adjusted regressions using percentage point (ppt) change in prevalence/incidence from 2004 to 2009 as the dependent variable and the level of prevalence/ incidence in 2004 as the independent variable. The adjusted model included socioeconomic, demographic, and behavioral factors, and accounted for spatial autocorrelations. From 2004 to 2009, the county-averaged diabetes prevalence/incidence increased by 2.1/0.07 ppt, respectively, and rate of increase over time For author disclosure information, see page 829. Guided Audio Tour poster A415 POSTERS Characteristics Epidemiology/ Genetics Purpose: To assess utilization patterns (adherence, type of index antidiabetic agent (ADA) and treatment modification) of glucagon-like peptide-1 agonists (GLP-1a) (exenatide, liraglutide), dipeptidyl-peptidase-4 Inhibitors (DPP-4i) (sitagliptin, saxagliptin, linagliptin) and other ADAs including insulin. Methods: A retrospective cohort study was conducted in the Thomson Reuters commercial health insurance database (2005-2011). Adherence, type of the index ADA (add-on, switch or new therapy), and treatment modification (discontinuation of index ADA, switching of index ADA, and add-on therapy) were assessed. Refill adherence was measured by Medication Possession Ratio (MPR). Results: We identified 208,683 DPP-4i users, 124,925 GLP-1a users and 1,187,502 other ADA users aged 18-64 years old. The majority of GLP-1a use was add-on and only 8% was new use. For DPP-4i, 58% were add-on and 15% were new use. Refill adherence (> 80%) was high for all 3 cohorts. Discontinuation rate was highest among GLP-1a (81%) and lowest among DPP-4i (69%). 35% of GLP-1a users switched to another class of medication compared to 20% of DPP-4i and 16% of other ADA. Conclusions: GLP-1a and DPP-4i are most commonly used as add-on to existing therapy. The most common adherence problem was medication discontinuation, particularly among GLP-1a users, whereas gaps between medication refills were not a common problem. EPIDEMIOLOGY—OTHER decreased. Counties with the greatest prevalence change were mostly in the South and those with the greatest incidence change were mostly in the Northeast. For each ppt in 2004 prevalence, the unadjusted annual change in prevalence increased by 0.04 ppt, implying faster increase in higher prevalence counties and a widening of prevalence disparity. Prevalence increases in the South and decreases in the West drove the widening disparities. However, for each ppt of prevalence in 2004, the adjusted annual change in prevalence decreased by 0.09 ppt, indicating that socioeconomic, demographic, and behavioral changes drove the observed change. In comparison, for each ppt in 2004 incidence, the unadjusted and adjusted annual changes in county-level incidence decreased, by 0.07 and 0.14 ppt, respectively, implying a slower rate of increase in high incidence counties and resulting a narrowing of incidence disparity. This was primarily driven by incidence decreases in the Northeast, Midwest and South and increases in the West. Interventions that target modifiable characteristics, such as education, obesity, and physical inactivity, could further reduce disparities in incidence and, over time, in prevalence. Table 1. Mean Changes in SBP, LDL-c and TG Baseline HbA1c Baseline HbA1c ≤ 7% 7.1-9.9% SBP LDL-c / TG SBP LDL-c / TG Pre- Ramadan 131.93 2.69 / 1.48 133.27 2.71 / 1.69 During Ramadan 130.17* 2.67 / 1.34* 130.86* 2.79 / 1.60 Post- Ramadan 132.59* 2.55 / 1.37 133.17* 2.57* / 1.44* Pre-Ramadan and post-Ramadan were defined as 6 months before and after Ramadan. The measurements of SBP and LDL-c/TG are in mm Hg and mmol/L, respectively; *p<0.05. 1593-P Psychometric Properties of the Hypoglycemia Perspectives Questionnaire (HPQ) in Type 2 Diabetes Mellitus ARIANE KAWATA, SIEW HWA ONG, CHRISTINA THERAPONTOS, PETROS MAVROGENIS, KAROLY KULICH, WEN-HUNG CHEN, KARIN COYNE, Bethesda, MD, Basel, Switzerland, Nicosia, Cyprus 1591-P Ethnic Disparities in Diabetes Risk Irrespective of Degree of Obesity The Hypoglycemia Perspectives Questionnaire (HPQ) was developed with clinician and patient input to assess symptoms, behaviors, and impact of hypoglycemia on diabetic patients. HPQ was administered to adults with type 2 diabetes mellitus (T2DM) on antidiabetic treatment as part of a cross-sectional, epidemiological study evaluating hypoglycemia and health-related quality of life (HRQoL) in Cyprus. Demographic and clinical data were collected. Patients also completed Audit of Diabetes Dependent Quality of Life (ADDQoL-19), treatment satisfaction questionnaire, and EuroQol-5 Dimensions (EQ-5D). The original HPQ included 45 items rating current status/behavior related to hypoglycemia on an 11-point numeric rating scale and 7 descriptive hypoglycemia event frequency items. Analyses examined HPQ item performance, item reduction, and factor structure. Measurement properties (reliability, construct validity, known-groups validity) of the final HPQ were evaluated. 500 T2DM patients completed the HPQ; mean age 61±10 years; 32.6% women. Based on item evaluation, the original HPQ item pool was reduced to 22 items. Exploratory and confirmatory factor analysis identified 21 items contributing to 3 hypoglycemia domains (Symptoms [8 items], Compensatory Behaviors [7 items], Worry [6 items]) and a single-item of global symptom awareness. HPQ domains had high internal consistency (alpha=0.78-0.92). Construct validity was demonstrated by significant correlations between HPQ with HRQoL, treatment satisfaction, and health status. HPQ was also able to discriminate between known groups. Compensatory behaviors and symptom awareness were higher for patients with a recent low blood sugar event (p<0.001) and high symptom awareness corresponded to less concern about experiencing symptoms of low blood sugar and worry (p<0.05). These results provide preliminary evidence that HPQ is reliable and valid for assessing the experience and impact of hypoglycemia on T2DM patients. POSTERS JOSEPH NGUYEN, ANNE HELENE OLSEN, NANA KRAGH, THORKILD SØRENSEN, Copenhagen, Denmark, Søborg, Denmark, Frederiksberg, Denmark Epidemiology/ Genetics Baseline HbA1c ≥ 10% SBP LDL-c / TG 133.04 3.17 / 2.01 131.28 3.28 / 2.07 132.72 2.78 / 1.64 The prevalence of obesity is increasing around the world and is associated with a number of co-morbidities including type 2 diabetes (T2D). The risk of T2D also varies with ethnic group and part of the excess risk appears to persist after correction for Body Mass Index (BMI). Also, increasing BMI seems to have a greater effect in some ethnic groups than in others. We examined the association between BMI group, ethnic group and diabetes using the 2007-2008 and 2009-2010 NHANES cross-sectional surveys. We excluded participants who were ≤30 years old at the survey, pregnant, participated only in the interview, had self-reported diabetes diagnosis at ≤30 years, or were underweight (BMI <18.5 kg/m2). Logistic regression with the variables age, gender, waist circumference, BMI group and ethnic group and the endpoint diabetes was used. BMI was split into 5 groups: normal (18.5-24), overweight (25-29), and obesity class 1 (30-34), 2 (35-39), and 3 (40+). Ethnic groups were Non-Hispanic White, Mexican-American, Other Hispanic, Non-Hispanic Black, and Other Race. Diabetes was defined by either HbA1c >6.5%, FPG ≥126 mg/dL, a 2-hour OGTT ≥200 mg/dL, or selfreported diabetes. The OR for having diabetes with normal BMI as baseline increased from 1.05 (95%CI 0.84-1.31) in the overweight to 2.97 (95%CI 2.263.91) and 4.25 (95%CI 3.16-5.73) in obesity class 2 and 3, respectively. With non-Hispanic whites as baseline, the OR for having diabetes was around 2 for all other ethnic groups. Increasing BMI seems to have less influence on diabetes risk among Mexican-Americans than in the other ethnic groups, probably because Mexican-Americans have a 3 times higher risk than nonHispanic whites even at normal BMI (1.5 times higher in obesity class 2 and 3). It is unclear why there are such great ethnic differences in T2D risk, and better understanding of this may help preventing T2D in the various ethnic groups with an elevated risk. Supported by: Novartis Pharmaceuticals Corporation Supported by: Novo Nordisk A/S 1594-P Differences in Predictors of Breastfeeding among Women With and Without Diabetes during Pregnancy 1592-P Impact of Ramadan Fasting on Systolic Blood Pressure and Lipid Profile among Patients With Diabetes in Relation to their HbA1c Control REENA OZA-FRANK, RASHMI KACHORIA, Columbus, OH Women with diabetes during pregnancy exhibit lower breastfeeding rates, yet predictors of breastfeeding initiation among these women are limited. Ohio birth certificate data from 2006-2011 were used to build separate logistic regression models by diabetes status (no diabetes [NDM], gestational diabetes mellitus [GDM], or prepregnancy diabetes mellitus [PDM]) to examine predictors of breastfeeding (direct breastfeeding and/ or pumping) at discharge. Among 807,466 births from 2006-2011, 5.5% of women had GDM and 0.8% had PDM. Across all diabetes groups, women with less education, Cesarean section, previous live births, enrolled in WIC or Medicaid, or whose infants were admitted to the neonatal intensive care unit were less likely to be breastfeeding at discharge. Married women were more likely to be breastfeeding at discharge as were all race/ethnicities compared with non-Hispanic Whites. However, there were differences in breastfeeding by diabetes status by infant gestational age (GA), maternal age, and adequacy of prenatal care. Among NDM, infants born late preterm (34-36 weeks) [odds ratio: 0.8; 95% confidence interval: 0.8-0.9] or moderately preterm (32-33 weeks) [0.9: 0.9-0.9] were less likely to be breastfed compared with infants born at term (>37 weeks). Among GDM, infants born late preterm were also less likely to be breastfed [0.9: 0.8-0.9]; MELANIE SIAW, JIELIN TAN, DANIEL CHEW, DARREN SEAH, MATTHIAS TOH, JOYCE Y. LEE, Singapore, Singapore Due to the practice of fasting between sunrise and sunset, Ramadan is known to affect the blood glucose of Muslim patients with diabetes. However, little is known about its effect on other metabolic parameters such as the systolic blood pressure (SBP) and lipid profile. In this study, we aimed to elucidate the impact of Ramadan fasting on SBP, low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) in 5,172 Muslim patients from nine primary care facilities in Singapore in relation to the control of their baseline HbA1c. The mean age was 60 ± 10.65 years with 61.2% of female and 38.8% male. Mean SBP improved during Ramadan in all patients with significant reduction observed in those with baseline HbA1c <10% (p < 0.05). A trend of improvement in mean TG was also observed in all patients with baseline HbA1c < 10% while mean LDL worsened in patients with baseline HbA1c >7% during Ramadan. However, after adjusting for age, gender and HbA1c, only the changes in mean SBP and mean TG during Ramadan were found to be significant (Table 1). & For author disclosure information, see page 829. A416 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—OTHER 1.1 [CI: 1.065-1.143], p<0.001) and depression (adjusted OR: 1.1 [CI: 1.0281.178], p=0.006) were the only factors associated with significantly higher prevalence of SD. Presence of depression in patients with DM may exert detrimental effects on sexual function. Prompt identification of depressive symptoms in patients with DM may be of paramount importance for the detection of underlying SD. however, infants born moderately preterm were more likely to be breastfed [1.3:1.0-1.6]. NDM women aged <19 [0.8:0.7-0.8] and 20-24 [0.9:0.9-0.9] were less likely to breastfeed compared with women aged 25-34. There were no significant differences in breastfeeding by age among GDM or PDM. Finally, among NDM [0.8:0.7-0.8] or GDM [0.9:0.7-0.9], inadequate prenatal care was associated with lower odds of breastfeeding. Among women with PDM, predictors were mostly similar to women with NDM. However, additional efforts to increase breastfeeding among women with GDM and NDM based on infant GA and adequacy of prenatal care may be warranted. 1597-P Age Dependent Changes of Cadmium Content in Human Islets MALEK EL MUAYED, KEITH MACRENARIS, WILLIAM L. LOWE, Chicago, IL 1595-P Experimental evidence by us and others suggest a possible association between cadmium (Cd) accumulation and beta cell dysfunction and dysglycemia. Cd is reported to have a long biological half life of up to 20 years, leading to a gradual age dependent accumulation in various organs. The relationship between age and the concentration of Cd in human islets has so far not been reported. In the present study we examined the relationship between age and cadmium levels in human islets from 24 deceased US donors (gender: 11m, 11f, 2 undocumented, age 42.4, SD 12.0). The average islet Cd content was 27.6 nmol/gram lysate protein (SD 16.9). There was a significant linear correlation between age and islet Cd levels with a Pearson correlation coefficient of 0.51 (95% CI 0.13 to 0.76, P 0.012). For comparison, no significant correlation between age and other divalent metals including zinc (Zn), nickel (Ni), and copper (Cu) was found (mean concentrations: Zn 11932.8 +/- 1403.8, Ni 208.7 +/- 35.5, Cu 405.7 +/- 54.4 nmol/g protein). Accumulation of mercury (Hg) was not evident, except for two samples with detectable levels (5.05 and 4.68 nmol/g protein, detection limit 4 nmol/g protein). Given the significant, age dependent accumulation of Cd in islets, further studies examining a potential link to diabetes are warranted. Factors Associated With Achieving Target HbA1c Levels in People With Type 2 Diabetes Beginning Insulin Detemir Treatment: Findings From the A1chieve Study RACHID MALEK, NABIL K. EL NAGGAR, MOHAMMAD I HASAN, PRADANA SOEWONDO, SEI HYUN BAIK, PHILIP HOME, Sétif, Algeria, Jeddah, Saudi Arabia, Lahore, Pakistan, Jakarta, Indonesia, Seoul, Republic of Korea, Newcastle upon Tyne, United Kingdom Epidemiological data can provide information about the factors which influence attainment of good glycemic control in routine clinical practice. A1chieve was a non-interventional study in the non-Western world evaluating the safety and clinical effectiveness of insulin analog therapy in people with type 2 diabetes (T2DM). This subgroup analysis of 11619 people examined factors associated with attaining a target HbA1c level of <7.0 % (53 mmol/mol) 24 wks after starting insulin detemir (detemir) with/without oral glucose-lowering drugs. An HbA1c <7.0 % was achieved by 3655 people (32%) at 24 wks, compared with 390 people (3%) at baseline (baseline HbA1c 9.5[1.6] % [88.1[17.4] mmol/mol]). After adjustment for regional differences, the baseline factors independently associated with achieving target were HbA1c, PPG levels, and microvascular complications (Table). Baseline age, duration of diabetes, BMI, fasting plasma glucose, systolic blood pressure and total serum cholesterol were not predictors of achieving HbA1c target levels. In conclusion, in a global study in routine clinical practice, attainment of HbA1c <7.0 % with insulin detemir was related to overall and meal-time glucose control at baseline, and to microvascular complications. This emphasizes the importance of defeating clinical inertia in starting insulin if attainment glucose targets and prevention of complications is to be improved. Supported by: Novo Nordisk A/S Supported by: NIEHS/NIH (1K08ES020880-01 to M.E.M.) 1596-P The Impact of Depression on Sexual Dysfunction in Patients With Type 2 Diabetes Mellitus 1598-P Correlation between Hemoglobin A1c and Meteorological Parameters in Japan CHRISTOS SAMPANIS, BARBARA NIKOLAIDOU, IOANNA ZOGRAFOU, ELENI GAVRIILAKI, PANAGIOTA ANYFANTI, GEORGE TRIANTAFYLLOU, ARETI TRIANTAFYLLOU, BETINA HAIDICH, MICHALIS DOUMAS, KONSTANTINOS PETIDIS, STELLA DOUMA, Thessaloniki, Greece TAKAYUKI WATANABE, ERI UEDA, MIZUKI SAWAI, MAKIYO MIMURA, KIICHIROU HIRAISHI, Yokohama, Japan Hemoglobin A1c(A1c) has been reported to change by seasonal variation. But there is no report about the direct relationship between meteorological parameters and glycemic control. We studied the correlation between changes in A1c and meteorological parameters as follows: temperature, humidity, precipitation, hours of sunshine and atmospheric pressure month by month. We used 24,255 A1c (NGSP) data measured every visit from 841 patients with diabetes mellitus from January 2006 to September 2012 in our outpatients office. Meteorological data was gathered from the website of Yokohama local meteorological observatory in Yokohama, Japan. We calculated the correlation coefficients between the meteorological parameters and the difference between A1c and its yearly mean (১A1c). We also calculated the correlation coefficients between the ১A1c and meteorological parameters one to three months before because A1c is an indicator of glycemic control of two to three months. The ১A1c was negatively correlated with temperature and humidity with r =- 0.496 (p<0.001) and -0.482 (p<0.001) respectively. The ১A1c was most significantly correlated with temperature two months before (১A1c = - 0.0143temperature + 0.23, r =0.715, p<0.001). The ১A1c was positively correlated with atmospheric pressure three months before with r = 0.632 (p<0.001). The ১A1c was not correlated with hours of sunshine. The association between ১A1c and meteorological parameters except temperature and hours of sunshine was Diabetes mellitus (DM) is a disease of chronic nature severely affecting not only physical functions including sexual performance, but also psychological aspects of patients’ health. However, the association of mental health disorders with sexual dysfunction (SD) in patients with DM has not been thoroughly investigated. We studied the impact of psychological disorders (anxiety, depression) on SD in a sample of consecutive patients with type 2 DM attending the Diabetes Centre of the 2nd Propedeutic Department of Internal Medicine, Aristotle University, Hippocratio Hospital, Thessaloniki, Greece. The International Index of Erectile Function (IIEF) and the Female Sexual Dysfunction Index (FSFI) questionnaires were used to detect SD in male and female patients, respectively. The Hamilton anxiety scale questionnaire was used to measure anxiety severity, while depressive symptoms were evaluated with the Zung self-rating depression scale. In total, 360 patients, 220 females and 140 males, 71±9.6 years old, were included in the study. SD was detected in 85% of our sample, while anxiety and depression affected 35.8% and 11.4% of our population, respectively. SD was significantly associated with anxiety, depression, age, DM duration, systolic blood pressure, pulse pressure, hypertension, waist circumference, cardiovascular disease, smoking, glomerular filtration rate, and HbA1c. In the multiple logistic regression model, it was revealed that age (adjusted OR: ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A417 POSTERS Epidemiology/ Genetics Figure: Correlation between age and islet Cd content EPIDEMIOLOGY—TYPE 1 DIABETES essentially due to changes in temperature. The results are compatible with the studies showing that A1c is lowest in summer and highest in winter in both hemispheres. We conclude the cause of seasonal variation of A1c is not hours of sunshine but change in temperature. EPIDEMIOLOGY—TYPE 1 DIABETES Guided Audio Tour: Type 1 Diabetes Epidemiology (Posters: 1601-P to 1608-P), see page 17. POSTERS Epidemiology/ Genetics 1599-P & Association of Napping and Nighttime Sleep With Impaired Glucose Regulation, Insulin Resistance and Glycated Hemoglobin in Chinese Middle-Aged Adults Without Diabetes HbA1c and Mortality in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study of Type 1 Diabetes (T1D) GANG CHEN, HONGJIE CHEN, LIXIANG LIN, JUNPING WEN, Fuzhou, China RACHEL G. MILLER, TREVOR J. ORCHARD, Pittsburgh, PA Objective: The purpose of the study was to assess the relationship of napping and nighttime sleep with impaired glucose regulation (IGR), insulin resistance and glycated hemoglobin (HbA1c) in Chinese middle-aged adults without diabetes. Methods: This cross-sectional study included 7568 adults aged 40-65years in Fujian province, China from June 2011 to January 2012. Selfreported hours of daytime napping and nighttime sleep were obtained by questionnaire. Anthropometric, laboratory measurements were determined. The homeostasis model assessment of insulin resistance (HOMA-IR) index higher than 2.50 was defined insulin resistance. Odds ratios (OR) and 95% CI (Confidence Interval) were derived from multivariate logistic regression models. Results: After adjustment for potential confounders, OR of HbA1c >6.0% were 1.376(95%CI: 1.179-1.607) for those with ≤1h of napping and 1.361(1.124-1.649) for those with >1h of napping compared with those who did not nap. Similar associations were found between napping and IGR or insulin resistance. For nighttime sleep, subjects with shorter sleep had significantly higher OR of HbA1c and IGR compared with the reference group (≥8 to <9h), but not insulin resistance. Conclusions: Napping was associated with higher HbA1c, IGR and insulin resistance, whilst shorter nighttime sleep was correlated with HbA1c and IGR. Therefore, a healthy sleep habits may profit glucose metabolism in middle-aged Chinese adults without diabetes. Recent type 2 diabetes trials suggest intensive glycemic therapy may be detrimental. The DCCT/EDIC study demonstrates the value of intensive therapy starting in short duration T1D, but the impact of HbA1c on mortality in longer duration T1D is unclear. Thus we assessed all-cause and causespecific mortality by quintiles of both baseline and mean follow-up HbA1c in a cohort of adults with long-standing T1D. Data are from the EDC study of childhood-onset T1D (n=658, baseline mean age=27 yrs, T1D duration=19 yrs, 49% female). Deaths were classified by a physician committee after review of death certificates, hospital, autopsy, and coroner reports over a 22-yr follow-up into acute T1D complication, renal disease (RD) only, cardiovascular disease (CVD) only, RD and/or CVD, and “other”. The 22-yr incidence of all-cause mortality was 24.9%. All-cause mortality increased linearly across quintile of both baseline (p<.001) and mean (p=0.003) HbA1c. CVD-only mortality increased linearly across quintiles of mean (p<.001), but not baseline (p=0.24) HbA1c. Furthermore, for the combined category of RD and/or CVD deaths, mortality increased linearly across quintiles of both baseline (p<.001) and mean (p=0.01) HbA1c. No trends were observed for acute, RD-only, or “other”. These results suggest that, in the EDC study, mortality increased linearly with increasing HbA1c, with no evidence that those in the lowest quintile of HbA1c are at an increased risk of mortality. 1601-P 1600-P Positive Correlations of Liver Enzymes With Serum Glucose Aged Over 45 Years in Countryside of China XIE JUN HUI, LIU QIAN, YANG YAN, LIU ZHE LONG, ZHOU XIN RONG, YU XUE FENG, ZHANG MU XUN, YUAN GANG, HU SHU HONG, Wuhan, China Objective: To investigate the prevalence of diabetes (DM) and the association of liver transaminase and serum glucose over 45 years old in countryside of China. Methods: A cross-sectional survey of 10800 people aged over 45 years was undertaken in rural of HuBei province . Participants underwent an oral glucose-tolerance test(OGTT) . Liver transaminase (ALT,AST, γ-GT),HbA1c, blood lipid were measured .Meanwhile the participants were invited to attend a single examination and a standard questionnaire . Result: 1. The prevalence of IFG (impaired fasting glucose ), IGT(impaired glucose tolerance), IFG+IGT (impaired fasting glucose combined with impaired glucose tolerance) and DM were 3.99% , 11.77% , 2.6%, and 9.99% in the survey, respectively. 2. With the increase of ALT and γ-GT concentrations, OR for glucose increased gradually. By comparing patients in the highest quartile of γGT concentration. ALTconcentration with those in the lowest quartile , OR of GGT for IFG, IGT, IFG+IGT, and DM was 1.34(95%CI 0.96-1.87), 2.14(95%CI 1.75-2.61), 2.08(95%CI 1.37-3.16) , 4.81(95%CI 3.79-6.09); OR of ALT was 2.22(95%CI 1.53-3.22), 1.04(95%CI 0.83-1.32), 2.04(95%CI 1.26-3.28), 2.36 (95%CI 1.84-3.02) respectively . 3. The area under curve forγ-GT was 0.64 and for ALT was 0.57 for discriminating DM from normal condition. In ROC curve analysis, the optimal cut-off value for γ-GT to discriminate DM from normal condition was 16.5 IU with the sensitivity of 71.4% and the specificity of 48.6%. Conclusion: The prevalence of prediabetes and DM is relatively high over 45 years in countryside of China . Serum γ-GT concentrations were the most closely related to serum glucose in three liver transaminases and were independently associated with prediabetes and diabetes. & 1602-P Impaired Renal Function Further Increases 6 Year Coronary Artery Calcification Progression in Type 1 Diabetes DAVID M. MAAHS, DIANA JALAL, MICHEL CHONCHOL, RICHARD JOHNSON, MARIAN J. REWERS, JANET K. SNELL-BERGEON, Aurora, CO Kidney disease increases cardiovascular risk in type 1 diabetes (T1D). We investigated whether baseline estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) independently predicted coronary artery calcification progression (CACp) over 6-years in adults with T1D compared to non-diabetics. All Coronary Artery Calcification in Type 1 Diabetes Study participants (n=1,066) with complete data for eGFR at baseline and 6 years were included. Three CKD-EPI equations (serum creatinine, cystatin C, and both) were used for eGFR. The association of baseline ACR and eGFR with CACp was analyzed using multiple logistic regression. Increasing categorical baseline ACR (<10, 10-30, and >30 µg/mg) predicted CACp in participants with T1D (Figure, OR=2.15, 95% CI: 1.50-3.09; OR=7.19, 95% CI: 3.90-13.26; OR=18.09, 95% CI: 8.48-38.62, respectively), compared to non-diabetics. T1D adults with baseline eGFR < 60 ml/min/1.73m2 had 5-7 times higher odds for CACp than non-diabetics with a J-shaped association for CKD-EPI serum creatinine and a step-wise association for CKD-EPI cystatin C. While increasing ACR and/or decreasing eGFR predict CACp, coronary atherosclerosis progresses faster in people with T1D even in the absence of Supported by: Chinese Medical Association & For author disclosure information, see page 829. A418 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—TYPE 1 DIABETES Overall, standard classifications underestimated the proportion of CVD attributable deaths by 43.7% between 1997-2007, with no significant change in this over time. The proportion of deaths attributed to CVD and diabetes among people with type 1 diabetes has decreased over time. However, we have shown that we may be underestimating the total burden of CVD mortality if we use traditional coding and only consider the underlying COD. Accurate assessment of the total CVD burden in people with diabetes is important for appropriate health care allocation and requires an approach that fully recognises the impact of CVD. diabetic kidney disease. These findings emphasize the interaction between kidney and cardiovascular disease in T1D and highlight the public health importance of lowering cardiorenal risk in people with T1D. Supported by: NHMRC (Australia) & Supported by: NIDDK; NHLBI 1603-P Type 1 diabetes (T1D) is characterized by the loss of pancreatic islet beta cell function resulting in loss of insulin production. Genetic and environmental factors may trigger an immune response targeting beta cells thus generating islet antibodies (IA). Immune response pathways involve a cascade of events, initiated by cytokines and chemokines, producing inflammation which can result in tissue damage. A nested case-control study was performed to identify temporal changes in cytokine levels in 75 DAISY subjects: 25 developed diabetes (T1D), 25 developed persistent IA but not T1D (IA), and 25 were controls. Serum samples were selected at four time points: T1-the earliest available sample (1-2 yr of age), T2-just prior to IA, T3-just after development of IA, and T4-prior to diagnosis of T1D or the most recent. Cytokines (Interferon [IFN]-α2a, interleukin [IL]-6, IL-17, IL-1β, interferon gamma-induced protein [IP]-10, monocyte chemotactic protein [MCP]-1, IFN-γ, IL-1α, and IL-1ra) were measured using the Meso Scale Discovery system Human Custom Cytokine 9-Plex assay. In multivariate mixed models adjusting for HLA risk, first degree relative status, age, and gender, MCP-1 (p=0.02), IFN- (p=0.008), and IL1β (p=0.0495) were significantly higher at T3 in TID when compared to IA subjects . At T4, IP-10 was significantly higher in IA subjects than controls (p=0.034), and IL-17 (p=0.03) and IL-1α (p=0.03) were higher in T1D subjects than controls.In this repeated measures nested case-control study, we identified increased inflammatory markers in children with IA who went on to develop T1D than among children who remained antibody positive but did not progress to clinical disease, as well as increased inflammation in both T1D and IA children at the last study time point when compared to control children. These results suggest that inflammation may be related to both the development of antibodies and the progression from antibodies to clinical T1D. Mortality from type 1 diabetes (T1D) is reported to be three times as high among Blacks than Whites. Socioeconomic status (SES) and access to health care may influence these racial differences. We sought to determine if survival differs between Blacks and White adults with long-standing T1D and with similarly low SES and access to health care. For a cohort of 391 (299 Blacks, 92 Whites) mostly low income adults aged 40-79 years with T1D recruited from government funded community health centers in the Southeast United States, we applied Cox proportional hazards models to estimate hazard ratios of subsequent all-cause mortality among Blacks compared with Whites. We also calculated standardized mortality ratios to compare the mortality experience of the individuals with T1D with the national and with the general community health center sex-race specific population norms. Mean age at diabetes diagnosis and baseline age at cohort entry, respectively, were 21 and 50 years in Blacks and 19 and 51 in Whites. During an average of 6.7 years of follow-up, 29% of the Blacks and 35% of the White population died. Median age at death was 53.4 years in Blacks and 53.3 years in Whites. In multivariable analysis adjusted for diabetes duration, sex, race, BMI, hypertension, high cholesterol, coronary artery disease, stroke/transient ischemic attack (TIA), a history of smoking, education, and income, only sex, BMI (U-shaped relationship), and a history of stroke/TIA predicted mortality. No difference in mortality risk was observed between Blacks and Whites (p=0.51). Compared to the racespecific U.S. general population, standardized mortality rates were 5.7 times higher in Blacks and 11.7 times higher in Whites. However, when compared to the same source population, i.e. the community health center population, mortality rates were 3.5 and 3.7 times higher in Blacks and Whites, respectively. Elevated mortality persists in adults with long duration of T1D, but given similarly low SES and access to health care, mortality rates are equally high among Blacks and Whites. Supported by: 2R01DK032493-28 Supported by: NIH (R01CA092447) & & 1604-P Accurate Estimation of CVD Mortality in People With Type 1 Diabetes TESSA L. CRUME, RICHARD F. HAMMAN, SCOTT ISOM, JASMIN DIVERS, ELIZABETH J. MAYER-DAVIS, WENZE ZHONG, SHARON H. SAYDAH, DEBRA A. STANDIFORD, JEAN M. LAWRENCE, CATHERINE PIHOKER, DANA DABELEA, Aurora, CO, Winston-Salem, NC, Chapel Hill, NC, Atlanta, GA, Cincinnati, OH, Pasadena, CA, Seattle, WA JESSICA L. HARDING, JONATHAN E. SHAW, DIANNA J. MAGLIANO, Melbourne, Australia Evidence suggests that cardiovascular disease (CVD) mortality in people with diabetes is decreasing. However, few national studies have examined mortality trends in type 1 diabetes. Further, since diabetes can be listed as the underlying cause of death (COD), when the death certificate indicates that a CVD event was due to diabetes, there may be classification errors in the literature. The aim of this study was to examine mortality trends in type 1 diabetes and to explore potential misclassification issues. The study included 166,177 people with type 1 diabetes registered on the Australian National Diabetes Service Scheme between 1997 and 2007. Vital status and COD were collected by linkage to the National Death Index. Deaths were coded according to ICD-10. Using standard classifications, the proportion of deaths from CVD decreased between 1997 and 2007 from 31.0% to 24.6% (ptrend <0.001), and the proportion due to diabetes decreased from 24.9% to 20.8% (ptrend <0.001). After recoding CVD deaths previously attributed to diabetes as CVD deaths, diabetes decreased from 11.6% to 9.4% (ptrend <0.001). Contrastingly, the proportion of diabetes deaths decreased upon recoding, but over time still decreased from 11.6% to 9.4% (ptrend <0.001). ADA-Funded Research & 1606-P The Accuracy of Provider-Diagnosed Diabetes Type in Youth: Evidence from the SEARCH Study One of the main challenges in establishing a sustainable surveillance system for diabetes in youth is accurate assessment of diabetes type. The aim of this study was to evaluate the accuracy of provider-diagnosed diabetes type abstracted from medical records compared to an etiologic assessment based on two criteria: autoimmunity indicated by the presence of GAD65 or IA2 diabetes autoantibodies (DA); and insulin sensitivity (IS) from an equation validated against euglycemic-hyperinsulinemic clamps. Measures of accuracy for 2349 SEARCH youth < 20 years of age at diagnosis in 2002-2006 are provided in Table 1. Provider-diagnosed type 1 diabetes (T1D) was highly sensitive (97%), but less specific (77%), had a positive predictive value (PPV) of 96% and negative predictive value (NPV) of 80% compared to an etiologic definition including DA positive, regardless of IS status, or presence of IS, if DA were not detected. Provider-diagnosed type 2 diabetes (T2D) had lower sensitivity (76%) but high specificity (97%), a PPV of 83%, and a NPV of 96% compared to the etiologic definition of DA negative and insulin resistance. In conclusion, provider-diagnosed diabetes type from medical records is reasonably accurate at identifying T1D but For author disclosure information, see page 829. Guided Audio Tour poster A419 POSTERS KATHLEEN C. WAUGH, JANET K. SNELL-BERGEON, FRAN DONG, IMAN TAKI, MICHELLE HOFFMAN, MARIAN J. REWERS, Aurora, CO BAQIYYAH CONWAY, THOMAS ELASY, MICHAEL E. MAY, WILLIAM J. BLOT, Morgantown, WV, Nashville, TN Epidemiology/ Genetics & Mortality by Race in Type 1 Diabetes 1605-P Increased Inflammation Is Associated With Islet Autoimmunity and Type 1 Diabetes in the Diabetes Autoimmunity Study in the Young (DAISY) EPIDEMIOLOGY—TYPE 1 DIABETES insufficient at capturing T2D in youth therefore periodic validation against etiologic diabetes type will be an important component of a sustainable surveillance system in the U.S. Table. Performance of published algorithms for case ascertainment using electronic health data from the University of North Carolina Health Care System’s Data Warehouse (source population, n=57,767; total presumptive cases n= 1348; total true cases n=537) description N FP Se Sp PPV NPV Algorithm n(%) (%) (%) (%) (%) # (Name, location, age range) 704 201(28.6) 93.7 99.6 71.4 99.9 1 (Klompas, A1c ≥ 6.5% or FPG ≥ 126 mg/dl or Massachusetts US, ≥ 2 ICD-9 codes 250.xx or DM no age limit) medications¶ at any time 2 (Dart, Manitoba ≥ 1 hospitalizations or ≥ 2 physician 810 309(38.1) 93.3 99.5 61.9 99.9 Canada, 1-18 yr) claims or ≥ 1 prescription claims in 1 year 3 (NDSS, Canada, start- ≥ 1 hospitalizations or ≥ 2 physician 501 25(5.0) 88.6 99.9 95.0 99.9 ing at 1 yr) claims in 2 years 4 (Guttmann, Ontario ≥ 2 physician claims in 2 years 493 19(3.9) 88.3 99.9 96.1 99.9 Canada, 0-18 yr) 5 (Guttmann, Ontario ≥ 4 physician claims in 2 years 428 3(0.7) 79.1 99.9 99.3 99.8 Canada, 0-18 yr) 6 (Harris, Ontario ≥ 2 abnormal plasma glucose tests 1348 811(60.2) 100.0 98.6 39.8 100.0 Canada, age not or A1c ≥ 6.5% or insulin or ≥ 2 oral specified) anti-diabetic drugs or diabetes on the problem list in 2 years Abbreviations: A1c, HbA1c; DM, diabetes mellitus; FPG, fasting plasma glucose; FP, false positive; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value. ¶ Klompas algorithm doesn’t include metformin and insulin use during pregnancy. 1. Klompas et al. Diabetes Care. 2012 Nov 27. [Epub ahead of print] 2. Dart AB, et al. Diabetes Care 2011; 34(4): 898-903. 3. NDSS. http://www.phac-aspc.gc.ca/publicat/2009/ndssdic-snsddac-09/ pdf/report-2009-eng.pdf 4&5. Guttmann A et al. Pediatr Diabetes 2010; 11(2): 122-128 6. Harris SB et al. BMC Health Serv Res 2010; 10: 347-352 Table 1. Comparison of provider diagnosed diabetes type compared to etiologic type in SEARCH Etiologic T1D Total Measures of Accuracy for T1D + Sensitivity = 96.5% Provider diagnosed T1D + 1929 81 2010 Specificity = 76.9% from medical record 69 270 339 PPV = 95.9% Total 1998 351 2349 NPV = 79.6% Provider diagnosed T2D from medical record Total Etiologic T2D + + 266 53 Total Measures of Accuracy for T2D Sensitivity = 75.8% 319 Specificity = 97.3% - 2030 2349 85 351 1945 1998 PPV = 83.4% NPV = 95.8% Supported by: CDC POSTERS Epidemiology/ Genetics & 1607-P Testing Childhood Diabetes Case Ascertainment Methods Based on Published Algorithms: The SEARCH for Diabetes in Youth Study, Carolina Site WENZE ZHONG, EMILY R. PFAFF, JOAN THOMAS, LINDSAY M. JAACKS, TIMOTHY S. CAREY, DANIEL P. BEAVERS, SHARON H. SAYDAH, JEAN M. LAWRENCE, RICHARD F. HAMMAN, DANA DABELEA, CATHERINE PIHOKER, ELIZABETH J. MAYER-DAVIS, Chapel Hill, NC, Winston-Salem, NC, Atlanta, GA, Pasadena, CA, Aurora, CO, Seattle, WA Supported by: CDC This study compares published case ascertainment methods for childhood diabetes (DM) surveillance. Using electronic health data from the University of North Carolina Health Care System’s Data Warehouse, we identified 57,767 children aged 0-19 years who had a physician visit for any reason in 2011. From among this group, we selected 1348 who met ≥ 1 of the following criteria since July 1st , 2008: 1) HbA1c ≥ 6.0%; 2) ≥ 1 fasting glucose ≥ 126mg/dl or ≥ 2 random glucose ≥ 200mg/dl on different days; 3) ≥ 1 DMrelated ICD-9 codes on problem list; 4) ≥ 1 DM-related ICD-9 billing codes; 5) any DM medications. The inclusion criteria ensured a high sensitivity. Medical record reviews conducted for 1348 presumptive cases yielded 537 true DM cases, with the remaining 57,230 considered to be true negatives. Using this cohort, we evaluated the performance of 6 published algorithms (table). For algorithm 6, sensitivity was 100%, but the positive predictive value (PPV) was only 39.8%. Algorithm 1 and 2 had similar sensitivity but algorithm 1 had better PPV (71.4% vs 61.9%). Algorithm 3 is used for national diabetes surveillance in Canada; its performance was good in our system as well. However, none of the algorithms had both high (>90%) sensitivity and PPV simultaneously. Results of algorithms may differ based on population characteristics. Work to refine these approaches and to categorize diabetes by type is ongoing. & 1608-P Age, Glycemic Control and Social Deprivation Independently Predict 10-Year Mortality in a UK Type 1 Diabetes Cohort DAVID HOPKINS, LAURA YASSA, DANIEL SIMPSON, AMANDA SIMONDS, STEPHANIE A. AMIEL, STEPHEN M. THOMAS, London, United Kingdom, Crawley, United Kingdom To determine the factors influencing poor outcomes in type 1 diabetes (T1D) we have conducted a retrospective analysis of combined biochemical, demographic and health resource utilisation data collected over a 10 year period for a cohort of T1D patients (n=1038) attending two inner city specialist diabetes outpatient clinics. The cohort was defined to include all patients attending the service in 2002 with sequential HbA1c data available for each year from 2002 to 2004 and with on-going follow-up within the clinics until 2010. Baseline glycemic control was defined as an individual’s mean HbA1c for the period 2002-2004. Economic status was determined using the index of multiple deprivation (IMD) a weighted deprivation score derived from a national dataset based on postcode of residence. At baseline, mean (+SD) age was 41.6 + 12.3 years and duration of diabetes 16.1 +14.0 years. Mean HbA1c was 8.2 + 1.3. 37 deaths occurred in the cohort by December 2012 (3.6% total cumulative mortality). Patients who died were significantly older (50.9 + 9.1 vs 41.2 +12.2 years, p <0.001) and had higher mean baseline A1c (9.1 + 1.6 vs 8.2 + 1.3, p<0.001) but did not differ in duration of diabetes (14.8 + 15.7 vs 16.1 + 14.0, p=0.8). For individuals with baseline HbA1c > 9.0%, cumulative 10-year mortality was significantly increased at 9.0 % (p< 0.001). Patients who died were more likely to be socially deprived, 61% of deceased patients having scores in the upper quintile of the population range (mean IMD score 32.3 + 11.2 deceased vs 23.6 + 12.3 alive, p=0.001 ). In a three step regression analysis, baseline HbA1c, age and IMD score were independent predictors of mortality. These data indicate the significance of glycemic control and social deprivation as independent, potentially modifiable risk factors for mortality in type 1 diabetes. Supported by: Novo Nordisk, Inc. & For author disclosure information, see page 829. A420 Guided Audio Tour poster ADA-Funded Research 1611-P Insulin Resistance and Fasting Plasma Glucose in First Degree Relatives of Patients With Type 1 Diabetes ANDREA STECK, FRAN DONG, IMAN TAKI, MICHELLE HOFFMAN, MARIAN J. REWERS, Aurora, CO KATARZYNA SIEWKO, ANNA POPLAWSKA-KITA, BEATA TELEJKO, AGNIESZKA NIKOLAJUK, MARIA GORSKA, MALGORZATA SZELACHOWSKA, Bialystok, Poland Earlier diagnosis and treatment of type 1 diabetes (T1D) may help preserve endogenous insulin secretion. However, an oral glucose tolerance test (OGTT) is a cumbersome and poorly reproducible criterion for early diagnosis of diabetes in high- risk subjects. Continuous glucose monitoring (CGM) technology offers an opportunity to improve diagnostic criteria. The Diabetes Autoimmunity Study in the Young (DAISY) follows prospectively high-risk children for development of T1D. Eleven DAISY children with persistent multiple islet autoantibodies (IA), but no signs or symptoms of diabetes, and eight controls used a Dexcom 7 CGM for a minimum of 4 days. Cases and controls had similar demographic characteristics. Cases showed more impaired glycemia with percent time spent above 140 mg/dl of 18 % compared to 6% in controls (p=0.04). The range of sensor values was significantly wider in cases versus controls (p = 0.03). The area under the curve (AUC) overall and during daytime, but not during night, was significantly greater in cases than in the controls (p ≤ 0.003). Of interest, the mean HbA1c in the cases was only 5.4%; 5/11 subjects had an OGTT during CGM: four had normal OGTT while one had impaired glucose tolerance. Two of the IA cases developed T1D 6 months after their CGM. Early hyperglycemia can be picked up by CGM and may help with earlier diagnosis of T1D. Revisions to the current ADA criteria for diagnosis of diabetes in children at high risk should be considered with more widespread access to CGM. CGM Mean glucose (mg/dl) SD (mg/dl) CV (mg/dl) Range (mg/dl) % Time > 140 mg/dl AUC (mg/min/dl) AUC day (mg/min/dl) Control (Mean + SD) 107 + 9 18 + 7 17 + 6 106 + 44 0.06 + 0.06 507028 + 38239 379792 + 27481 Case (Mean + SD) 117 + 14 26 + 9 22 + 7 154 + 48 0.18 + 0.17 601682 + 68777 459653 + 58657 Background: We analyzed the relationship between fasting plasma glucose (FPG), the presence of autoantibodies, first phase of insulin secretion and insulin resistance in the first degree relatives of patients with type 1 diabetes. Materials and methods: The group studied consisted of 90 healthy relatives, divided into two groups: “high-normal” FPG group (≥88 mg/dl) and “low-normal” FPG group (<88/mg/dl). All subjects underwent an intravenous glucose tolerance test, and the 1st phase insulin response (FPIR) and FPIR-toHOMA-IR-ratio were calculated. Additionally, islet autoantibodies (GADA, IAA and IA-2A) were determined by radioimmunoassays. Results: The subjects with “high-normal” FPG were older (p=0.0009), had higher BMI (p<0.0001) and lower HOMA%B (p=0.0004), FPIR (p=0.006) and FPIR-to-HOMA-IR-ratio (p=0.004) in comparison with the “low-normal” FPG group. Autoantibodies were present in 40.9% and in 21,7% of the subjects with “high-normal” and “low-normal” FPG, respectively. In the “high-normal” FPG group, FPG correlated positively with GADA (r=0.31, p=0.04), and HOMA-IR (r=0.19, p=0.02), and negatively with HOMA%B (r =-0.36, p=0.001), whereas FPIR correlated positively with HOMA%B (r=0.55, p=0.0001) and BMI (r=0.30, p=0.04). After an adjustment for BMI, the difference in FPIR between the “high-normal” and “low-normal” FPG groups remained significant (p=0.025), whereas the difference in FPIR-to-HOMA-IRratio became insignificant. Conclusions: Our results suggest that taking into account the impact of age and BMI on insulin sensitivity, it would be expected that the relatives of patients with type 1 diabetes with “high-normal” glucose levels would become gradually unable to compensate for increasing insulin resistance. P value 0.075 0.062 0.075 0.026 0.04 0.003 <0.001 1612-P Increase in Weight but no Improvement in Glycaemic Control Over a Decade in Patients Living With Type 1 Diabetes Mellitus (T1DM) ANITA BOWES, ALEX HALE, JO HAVILAND, DAVID KERR, Bournemouth, United Kingdom Aims: To determine the long-term changes in weight and HbA1c in patients living with T1DM attending a specialist diabetes centre in the UK. Methods: Bournemouth Diabetes Centre maintains an electronic database of patients with T1DM with body weight and HBA1c recorded at each visit. The Centre offers (a) structured education programme for patients using multiple daily injections of insulin (EDU), (b) insulin pump therapy (PUMP) and (c) combination of EDU+PUMP. Non-participants of EDU, PUMP and ED+PUMP represented the BACKGROUND population. We compared annual changes in weight and HBA1c for these cohorts between 1999-2012. Longitudinal analyses of yearly observations were carried out using Generalised Estimating Equations and significance assessed by the Wald test. Results: 1503 patients (765 men), age 41 [±17] yrs, (mean[±SD]), diabetes duration 16 [±13] yrs were identified. Overall, there was a small annual increase in weight (+0.16 [95% CI +0.05,+0.27] kg/year, p=0.005). The greatest increase was in the EDU+PUMP group (n=102, +0.80 [95%CI +0.16,+1.43] kg/year, p=0.014) compared to PUMP (n=311, +0.33 [95%CI -0.03,+0.69] kg/year, p=0.075), EDU (n=311, +0.12 [95%CI -0.24,+0.49] kg/ year, p=0.504) and BACKGROUND (n=1278 +0.12 [95%CI -0.01, +0.26] kg/ year, p=0.080) groups. For all groups combined, there was no change in HbA1c over time adjusted for gender and age (p=0.432). However, the change between the groups in HbA1c was significant (p=0.035) with a rise in the EDU group (+0.06 [95%CI 0.02, 0.10] %/year, p=0.004) compared to BACKGROUND (+0.04 [95%CI -0.02, +0.03] %/year, p=0.76), PUMP (-0.01 [95%CI -0.04, +0.02] %/year, p=0.55), and EDU+PUMP (+0.11 [95%CI --0.07, +0.28] %/year, p=0.23) groups. Conclusion: For patients living with T1DM there is a small but consistent increase in weight over time. Glycaemic control does not change markedly with time and it may be worthwhile considering more intensive inputs to achieve longer term benefits. Supported by: NIH (R37DK32493) 1610-P Longitudinal Analysis of Adiponectin through a 20 Year Type 1 Diabetes Duration TAMARA J. LECAIRE, MARI PALTA, Madison, WI Adiponectin (ADPN) has been proposed to be an insulin sensitizer as well as a marker for inflammation and endothelial function. We examined the pattern of ADPN in type 1 diabetes with age and duration, and factors predictive of ADPN across 20 years duration. The Wisconsin Diabetes Registry conducted clinical exams at 1, 4, 7, 9 and 20 years diabetes duration. Twenty-year examinees (n=304) participated in (mean) 3.43 total exams yielding 1043 stored plasma samples tested for ADPN. Predictors of ADPN and tracking in individuals across time were determined by linear mixed regression models. A cross-sectional linear regression model at 20 years was fit for comparison. ADPN showed significant tracking (r=0.59) within individuals. Levels declined during childhood and adolescence. The difference between genders (females had higher levels) increased with age. Weight (kg) and waist circumference (cm) were negatively related with ADPN, each accounting for approximately 4% (95% CI 2.3-5.2% and 1.1-5.8%, respectively) lower ADPN per 5 unit increase. ADPN was higher by 4% (95% CI 2.4-5.6%) for 1% higher HbA1c and lower with greater insulin dose and longer duration (p=0.030). At 20 years duration, 1% change in urine albumin-creatinine ratio (UACR) was associated with an 8% increase in ADPN (95% CI 5.4-11.7%). Both levels and trends with duration varied significantly between individuals, with both positive and negative slopes over time, even after adjustment for all predictors. Markers for insulin resistance were associated with lower, and markers for potential microvascular complications with higher ADPN, supporting both pathways. Associations with HbA1c may represent yet another pathway. Our results indicate ADPN levels in T1DM may reflect 3 pathways. A positive relationship between ADPN and UACR that became stronger with duration may make it possible to identify those predisposed to develop kidney disease earlier in the course of the disease. Supported by: NIDDK (R01DK36904) ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A421 POSTERS 1609-P Early Glycemic Changes Detected by CGM in Children at Risk for Type 1 Diabetes Epidemiology/ Genetics EPIDEMIOLOGY—TYPE 1 DIABETES EPIDEMIOLOGY—TYPE 1 DIABETES 1613-P Adjusted Odds Ratios for the Achievement of Age-specific Target A1C Levels Model 1 Model 2 Model 3 (Age < 6) (Age 6 – 12) (Age > 12) n=123 n=453 n=805 Gender 1.00 1.00 1.00 Male 0.64 (0.29-1.41) 1.08 (0.74-1.58) 0.47 (0.29-0.77)* Female Age 1.49 (0.83-2.68) 0.94 (0.82-1.09) 1.21 (1.04-1.41) Distance from London < 50 km 1.00 1.00 1.00 > 50 km 0.35 (0.16-0.74)* 0.88 (0.60-1.28) 1.09 (0.69-1.74) Household Income < $57,000 1.00 1.00 1.00 > $57,000 0.85 (0.36-1.96) 1.18 (0.80-1.73) 1.15 (0.71-1.85) Diabetes duration 0.85 (0.58-1.24) 1.01 (0.92-1.10) 1.13 (1.06-1.21)* Body Mass Index 1.10 (0.77-1.59) 1.03 (0.98-1.09) 1.06 (1.01-1.12)* Attainment of the Previous Age-Specific Target A1C Level No N/A 1.00 1.00 Yes 1.26 (0.84-1.89) 1.95 (1.33-2.86) Note: Odds Ratio of 1.00 denotes reference category. 95% Confidence Intervals are shown in the brackets. * Denotes p=0.2 for a stepwise model building entry criteria A Decade of Temporal Trends in Overweight/Obesity in Youth With Type 1 Diabetes (T1D) Since the DCCT CHARU BASKARAN, MONICA M. DIAZ, LISA K. VOLKENING, LORI M. LAFFEL, Boston, MA POSTERS Epidemiology/ Genetics Youth with T1D are at risk for untoward weight gain due to the combined influences of the current epidemic of childhood overweight/obesity and greater use of intensive insulin therapy, which was associated with weight gain in the DCCT. We assessed use of intensive insulin therapy and weight status in 4 unique cohorts of T1D youth from 1999-2009. The 537 T1D youth (48% male) were 8-16 years old and had T1D for 0.5-15 years across all cohorts. Cohorts differed in age and T1D duration (Table); there were no significant differences in sex, race, or A1c. Intensive management increased significantly over time, noted by more frequent daily BG monitoring (p<.0001) and greater use of intensive insulin therapy, defined as 3+ injections/day or pump use, which increased from 51% to 96% (p<.0001). Overall, 1/3 of T1D youth were overweight/obese and zBMI was similar in all cohorts. In multivariate analysis, higher A1c was related to higher daily insulin dose (p<.004), less frequent BG monitoring (p<.0001), injection-based insulin therapy (p<.008), non-white race (p<.0001), and later cohort (p<.001) but A1c was not related to zBMI. zBMI was not related to intensive insulin therapy or cohort. Despite near universal intensive insulin therapy, prevalence of overweight/obesity in T1D youth remained stable over a decade, a pattern similar to the general pediatric population. However, A1c remains suboptimal in T1D youth, underscoring the need to reduce risk for future complications. Participant characteristics according to study cohort 1999 2002 2006 2009 (N=100) (N=153) (N=138) (n=146) Age (years) 12.1±2.3 12.9±2.3 12.1±1.9 13.5±2.4 T1D duration (years) 2.7±1.5 6.3±3.5 5.6±3.3 6.6±3.5 z-BMI (SDS) 0.7±0.8 0.8±0.7 0.6±0.8 0.7±0.8 Overweight/obesity (%) 18 / 10 25 / 12 26 / 7 22 / 13 BG monitoring (times/day) 3.6±0.7 3.8±1.2 5.2±2.1 5.2±2.2 A1c (%) 8.4±1.1 8.4±1.4 8.3±1.1 8.7±1.4 Regimen (Pump / ≥3 daily injections / 1 / 50 / 49 23 / 62 / 15 41 / 57 / 2 66 / 30 / 4 ≤2 daily injections) (%) 1615-P P value Trend of Type 1 Diabetes Mellitus Incidence in Children in Beijing Based on Hospitalization Data During 1995-2010 <.001 <.0001 .66 .5 <.0001 .18 <.0001 CHUN XIU GONG, XI MENG, BING YAN CAO, DI WU, Beijing, China The incidence of type 1 diabetes mellitus (T1DM) in children younger than 15 years is increasing. Our aim was to assess the trend of T1DM incidence in Beijing children since 1995 and to predict the number of T1DM in the future. We collected the newly diagnosed T1DM children younger than 15 years in Beijing Children’s Hospital in 1995-2010, calculated the incidence of Beijing children with T1DM, and defined it as the estimated incidence rate. The standard average estimated incidence was 1.3/100,000 during 19952010, increasing from 0.57/100,000 to 2.25/100,000. The estimated incidence increased in all age groups compared between 1995-2002 and 2003-2010: from 0.24/100, 000 to 0.57/100,000 in 0-4 years, from 1.31/100,000 to 2.12/100,000 in 5-9 years, from 1.25/100,000 to 1.86/100,000 in 10-14 years. The predicted number of new T1DM cases will increase 1.1 times and the percentage distribution of new cases will be 34.89% (<5 yrs), 37.08% (5-9 yrs) and 28.03% (10-14 yrs) in 2020. So in conclusion, The T1DM incidence of Beijing children definitely increased. The age group with greatest increase of estimated incidence was the younger than 5 years. The predicted new T1DM cases will be more even distribution across whole age-groups. Supported by: R01DK046887; Charles H. Hood Foundation 1614-P Predictors of Glycemic Control in Children and Adolescents With Type 1 Diabetes in Southwestern Ontario TAMARA SPAIC, STEWART B. HARRIS, JEFFREY MAHON, London, ON, Canada Optimal glycemic control in children with type 1 diabetes (T1D) is essential but often difficult to achieve. There are limited data on factors associated with suboptimal control under ‘real-world’ conditions. We performed a population based cohort study from 1998-2008 using a clinical database (Humabase) at the Children’s Hospital in London, ON. Over 80% of incident cases of T1D in Southwestern Ontario are followed in Humabase. Our goal was to identify factors that predicted attainment of Canadian Diabetes Association age-specific A1C targets (< 8.5% [0-6 years], <8 % [6-12 years], <7% [>12 years]) in routine clinical practice. Predictors of interest are listed in the Table. Relationships between these variables and reaching target A1C levels were assessed by multivariable logistic regression within each age group. There were 996 subjects (52 % male) aged 2-20 yrs with T1D for ≥ 1 yr (mean = 9 yrs) in the study. Proportions of subjects with target A1C levels at the last visit were 63 % < 6 yrs, 44 % 6-12 yrs, and 9.8% > 12 yrs. Results are shown in the Table. Distance from treatment center predicted target A1C those <6 yrs, while male gender, longer diabetes duration, and higher BMI predicted target A1C levels among adolescents. This first Canadian study using a regional pediatric T1D clinical database suggests that attainment of target A1C levels in routine practice is sub-optimal, particularly in adolescents, and that a limited number of factors influence glycemic control. 1616-P Residual C-Peptide in Patients 3-81 Years from Diagnosis of T1D: A T1D Exchange Study ASA DAVIS, MICHAEL J. HALLER, KELLEE MILLER, STEPHANIE DUBOSE, CHRISTINA CARPENTER, LINDA DIMEGLIO, DAVID R. LILJENQUIST, ANDREW AHMANN, SANTICA M. MARCOVINA, CARLA GREENBAUM, ROY BECK, Seattle, WA, Gainesville, FL, Tampa, FL, Indianapolis, IN, Idaho Falls, ID, Portland, OR While robust data are available to describe the natural history of β-cell function in T1D immediately following diagnosis, limited data are available to describe persistence of β-cell function in those diagnosed with T1D for ≥ 3 years. Eight hundred and eighty eight T1D individuals from 27 T1D Exchange Clinics were stratified into 10 groups (100/group) by T1D duration and age of T1D onset (half diagnosed as adults >18 years). The prevalence of detectable C-peptide (>0.017 nmol/L) varied according to T1D duration and age at diagnosis (Figure). For most T1D duration groups, more of those diagnosed as adults had detectable C-peptide. In subjects diagnosed as children the percentage of individuals still making their own insulin remained constant (~7%) in 10-19, 20-40 and >40 years duration groups. Thus, frequency of persistent C-peptide in those >40 years from diagnosis was approximately equivalent between those diagnosed as children and those diagnosed as adults. & For author disclosure information, see page 829. A422 Guided Audio Tour poster ADA-Funded Research EPIDEMIOLOGY—TYPE 1 DIABETES Nearly 30 years after the start of the DCCT, the EDIC Study conducted a 4-hour mixed meal tolerance test in 58 patients selected to be most likely to have residual beta cell function based on a history of near/normal HbA1c throughout DCCT/EDIC and/or above average stimulated C-peptide at DCCT baseline. C-peptide was measured by chemiluminescent immunoassay. Of the 58 patients with an average duration of 27 (25 - 30) years, 10 (17.2%) showed a definite C-peptide response consisting of 2 or more poststimulus values > 0.03 nmol/L (Figure). All responders had a C-peptide > 0.2 nmol/L at DCCT baseline and were assigned to the intensive treatment group. An additional 4 subjects showed a probable response based on a rise in c-peptide levels post-stimulus, though the peak was in the range of 0.005 to 0.023 nmol/L. These results show that a stimulated C-peptide response can be measured, albeit at low concentrations, in some patients with long-term T1D. Further investigation of all surviving DCCT/EDIC patients will help relate residual C-peptide response to history of HbA1c, insulin dose, severe hypoglycemia, retinopathy, nephropathy and macrovascular disease. The frequency of residual C-peptide decreases with time from diagnosis regardless of age at diagnosis. Diagnosis during adulthood is associated with greater prevalence of C-peptide with the exception of those with duration of disease >40 years in which ~8-12% have C-peptide regardless of age at diagnosis. Identification of immunologic and clinical characteristics associated with retained insulin secretion over time is underway and will provide critical data for future possible intervention trials in this population. Supported by: Leona M. and Harry B. Helmsley Charitable Trust Epidemiology/ Genetics JEROME R. BARRERA, ELIZABETH PAZ-PACHECO, CECILIA A. JIMENO, Manila, Philippines Insulin resistance (IR) has been proven to increase the risks for cardiovascular complications in type 2 diabetes mellitus. Recently, IR has also been shown to play a bigger role in the natural history of type 1 diabetes mellitus (T1DM) disease process than is commonly recognized. The objectives of this study are to determine the prevalence of IR among Filipino adults with T1DM and to describe the clinical features of T1DM with IR. This cross-sectional analytic study recruited 83 adults with established T1DM in Philippine General Hospital. Mixed-meal stimulated C-peptide level was done to confirm the diagnosis of T1DM. IR was determined using estimated glucose disposal rate (eGDR) with the formula of: eGDR= 24.31 - (12.22 x Waist-to-hip ratio) - (3.29 x 1 if with hypertension or on antihypertensive or x 0 if no hypertension) - (0.57 x HbA1c). Subjects with eGDR of ≤ 7.5 mg/kg/min were considered to have IR. The prevalence rate of insulin resistance was found to be 53% among adults with established type 1 diabetes mellitus. Type 1 diabetic subjects with insulin resistance were significantly older (29.59 vs 25.59, p = 0.007), with longer duration of diabetes (59.7% vs 40.3 % with duration of diabetes > 5yr, p = 0.037), with higher waist-to-hip ratio (0.95 vs 0.93, p = 0.005) and with higher prevalence of hypertension (100% vs 0%, p = 0.00) than those without insulin resistance. T1DM with insulin resistance tend to have higher insulin requirement per day, poor glycemic control and higher BMI than those T1DM with no insulin resistance these were not significantly different. The result of this study showed a high prevalence rate of insulin resistance among Filipino adults with long standing type 1 diabetes mellitus. Hypertension, older age, longer duration of disease and a higher waist-to-hip ratio are the features more common in type 1 diabetic patients with insulin resistance than those without insulin resistance. Supported by: NIH 1619-P Increasing Prevalence and Younger Age at Onset of Type 1 Diabetes in Migrant than Italian Children With Type 1 Diabetes: An Emerging Problem FRANCESCO CADARIO, GRAZIELLA BRUNO, FRANCO CERUTTI, SILVIA SAVASTIO, STEFANO TUMINI, ITALIAN SOCIETY OF PEDIATRIC ENDOCRINOLOGY AND DIABETOLOGY STUDY GROUP (SIEDP), Novara, Italy, Turin, Italy, Chieti, Italy The worldwide increasing incidence of type 1 diabetes (T1DM) is due to the interaction between environmental determinants and genetic susceptibility, probably promoting β-cell autoimmunity in early childhood. Epidemiological studies on people migrated represents a unique opportunity to test the effect of enviromental modification on incidence of T1DM. In Italy, a three-fold increase in the number of migrants, particularly in the youngest age groups occurred in the last two decades. The Italian Society of Pediatric Endocrinology and Diabetology Study Group (ISPED) performed a clinic-based, multicentre study including 36 pediatric outpatients clinics, to examine the burden of the disease in migrated children on our health care system. Of 4674 children, aged 0-14 years currently cared for T1DM, 720 were from families who migrated to Italy, 33.3% from Morocco, 11.0% Romania, 6.8% Albania, 45.6% from other countries at lower risk of T1DM (Eastern Europe, Latin America, Asia) and 4.3% only from higher risk European countries. The prevalence of migrated children with T1DM has increased five-fold, from 3.4% to 15.4% and most of diabetic children (71.7%) were born in Italy. Mean age at onset of T1DM was lower in migrated children born in Italy than in Italian children (5.2 years, IQR 2.3-7.7 vs 9.8 years, 5.9-13.0; p<0.001), whereas it was higher in migrated children who were born in their original countries (7.8 years, 4.6-10.4). Epidemiological studies have shown a shift to earlier age of onset of type 1 diabetes in EastCentral Europe and a doubling of incidence in children younger than 5 years is predicted between 2005 and 2020 in Europe. Although a rise in incidence in very young children has not been observed in Italy, environmental factors operating in this age group might be similar. A poor socioeconomic status with overcrowding may expose to a greater risk of perinatal infection with diabetogenic microorganisms triggering β-cell autoimmunity. Supported by: Philippine Society of Endocrinology and Metabolism 1618-P Residual Beta Cell Function in Patients With Long-Term Type 1 Diabetes ROSE A. GUBITOSI-KLUG, PAULA MCGEE, MARGARET BAYLESS, MAREN NOWICKI, PATRICIA A. CLEARY, MICHAEL W. STEFFES, JOHN M. LACHIN, JERRY P. PALMER, DCCT/EDIC RESEARCH GROUP, Cleveland, OH, Rockville, MD, Iowa City, IA, Minneapolis, MN, Washington, DC, Seattle, WA The benefits of a stimulated C-peptide response early in T1D include the ability to achieve optimal glycemic control with less hypoglycemia and to reduce the development and progression of retinopathy and nephropathy. However, C-peptide secretion declines over time, and it is not known whether stimulated C-peptide is common after long-term diabetes. ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A423 POSTERS 1617-P Insulin Resistance among Adults With Type 1 Diabetes Mellitus at the Philippine General Hospital GENETICS—TYPE 1 DIABETES GENETICS—TYPE 1 DIABETES & Guided Audio Tour: Genetics of Type 1 Diabetes and Related Traits (Posters: 1620-P to 1627-P), see page 17. & GARETH J. MCKAY, DAVID H. KAVANAGH, DAVID A. SAVAGE, CHRISTOPHER C. PATTERSON, AMY J. MCKNIGHT, JOHN K. CREAN, JOSE C. FLOREZ, ALEXANDER P. MAXWELL, THE WARREN 3/UK GOKIND STUDY GROUP, Belfast, United Kingdom, Dublin, Ireland, Boston, MA 1620-P Non-Synonymous Single Nucleotide Polymorphisms in the IA-2 Gene Improve Prediction of Type 1 Diabetes Both glomerular sclerosis and renal interstitial fibrosis are characteristic of diabetic nephropathy (DN) with several studies implicating members of the WNT signalling pathways in these pathological processes. Our study sought to comprehensively study common genetic variants in the WNT pathway for association with DN. More than 65 genes have been implicated in the WNT pathways. Genes were selected for analysis on the basis of nominal significance and consistent direction of effect within each of the 3 independent cohorts used in the GENIE genome-wide association study (GWAS) meta-analysis dataset. Common SNPs and inferred haplotypes not available from the GWAS data were examined within selected genes in a white population with type 1 diabetes, discordant for DN (cases: n=718; controls: n=749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate. A logistic regression model including collection center, duration of diabetes, and average HbA1c as covariates highlighted three SNPs in GSK3B (rs17810235, rs17471, rs334543), two in DAAM1 (rs1253192, rs1252906) and one in NFAT5 (rs17297207) as being significantly (P<0.05) associated with DN, although these SNPs did not remain significant following correction for multiple testing. Logistic regression analysis of haplotypes with ESRD and pairwise interaction analyses failed to identify significant association following correction for multiple testing. Our results suggest that both common SNPs and haplotypes of WNT signalling pathway genes are not strongly associated with DN. Nonetheless, this does not completely exclude these or indeed the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could potentially contribute to the genetic architecture of this diabetic complication. POSTERS Epidemiology/ Genetics MICHAEL P. MORRAN, SANTIAGO SCHNELL, YING-JIAN ZHANG, LIPING YU, DOROTHY J. BECKER, MASSIMO PIETROPAOLO, Ann Arbor, MI, Aurora, CO, Pittsburgh, PA The neuroendocrine tyrosine phosphatase-like protein IA-2 is a transmembrane glycoprotein localized in the secretory granules of β-cells and a major autoantigen in type 1 diabetes (T1D). Autoantibodies (Ab) to IA-2 are utilized to identify subjects at risk of developing T1D for enrollment in prevention trials. Our full length IA-2 nucleotide sequence contains three validated non-synonymous SNPs (listed in SNP Consortium and Celera databases) (SNP-IA-2; aa residues 27, 608, and 671). Protein sequence and folding analysis indicates that the IA-2 variants influence the overall folding of SNP-IA-2 and create potential new Ab-protein interaction sites compared to native IA-2. Serum samples were evaluated in 333 relatives of T1D patients (102 of whom were initially normoglycemic prediabetics before they progressed to T1D; follow-up range 0.1-20.8 yr; median follow-up 6.1 yr) and 87 newly diagnosed T1D patients. SNP-IA-2 (and conventional IA2ic, ICA512bdc constructs), GAD65 and insulin Ab were assayed in these subjects. The cutoff point for the SNP-IA-2 Ab assay was established as the 99th percentile of 308 healthy control values. The prevalence of Ab to SNP-IA-2 was 60% in new onset T1D and 36.2% in prediabetics respectively. Kaplan and Meier analysis revealed that a subgroup subjects with no detectable Ab against the conventional constructs (IA-2ic or ICA512bdc) exhibited Ab responses toward SNP-IA-2 (Log rank, P = 0.008). This effect was also observed in relatives positive for GAD65 (Log rank, P = 0.026) or at least 2 non-IA-2 related autoantigen constructs (Log rank, P = 0.022). This subgroup of subjects with Ab to SNPs-IA-2 exhibited a very high risk as well as rapid progression to T1D onset. This finding may provide a mechanistic link in the search for new pathogenic IA-2 epitopes associated with disease progression. Identification of sequence variants of IA-2 may lead to advances in peptide-based immunotherapies targeted to prevent T1D at its preclinical stage. Supported by: Northern Ireland Kidney Research Fund & Supported by: NIDDK/NIH & 1622-P Genetic Association Analysis of WNT Signalling Pathway Genes in Diabetic Nephropathy 1623-P Impairment of DNA Repair Pathway as a Novel Mechanism Underlying Diabetic Complications in Patients With Longstanding Type 1 Diabetes 1621-P The RBP-Jk Type 1 Diabetes Susceptibility Allele Is Associated With an Alteration in Memory CD4+ T Cells SHWETA BHATT, RACHAEL MARTINEZ, TOMOZUMI TAKATANI, MARINA A. GRITSENKO, WEI-JUN QIAN, BRIDGET K. WAGNER, CHONG WEE LIEW, HILLARY KEENAN, GEORGE L. KING, AMY J. WAGERS, ROHIT N. KULKARNI, Boston, MA, Richland, WA, Cambridge, MA WASSIM ELYAMAN, WILL ORENT, RIBAL BASSIL, PHILIP DE JAGER, SAMIA KHOURY, ELIZABETH BRADSHAW, Boston, MA Recent genome-wide association studies (GWAS) identified a susceptibility locus, rs10517086AA that implicates the recombinant binding protein for immunoglobin kappa J region (RBP-Jκ) gene as a risk factor for type 1 diabetes (T1D) (combined P value of genome-wide association studies and replication = 4.6x10-10) and rheumatoid arthritis. We have shown that RBP-Jκ, a downstream transcription effector of Notch signaling, is a positive regulator of interleukin (IL)-9 transcription, therefore we examined the biologic phenotypes of healthy subjects selected from the PhenoGenetic cohort at Brigham and Women’s Hospital, based on homozygousity for the risk or protective allele. We found that healthy subjects homozygous for the rs10517086AA risk allele have increase mRNA expression of RBP-Jκ in CD4+CD45RO+ memory cells (n=8/genotype, p=0.02) but not CD4+CD45RO- naïve T cells relative to control subjects homozygous for the rs10517086GG protective allele. As a consequence, the cytokine profile of TCR-stimulated memory T cells carrying the rs10517086AA risk allele was marked by a specific increase in IL-9 production as measured by flow cytometry (n=14/group, p=0.01). We also found an increase in proliferation by the 3H-thymidine incorporation method. Interestingly, we did not detect any changes in other inflammatory cytokines including IL-4, IL-10, IL-17 and IFN-gamma. These findings are in agreement with our recent study demonstrating high levels of IL-9 in memory T-cells from T1D subjects polarized under Th17 cell conditions (Beriou et al, 2010). Our results point towards a correlation between rs10517086 and RBP-JK expression, T-cell activation and IL-9 production in CD4+CD45RO+ memory T-cells. These studies provide a rational approach for the dissection of the role of Notch signaling in T1D and may yield novel insights and targets that can be leveraged for the development of therapeutics for pre-symptomatic T1D. Type 1 diabetes (T1D) is associated with micro- and macro-vascular complications whose underlying molecular mechanisms remain elusive due to lack of cellular models that mimic in vivo disease phenotype. To circumvent this, we derived induced pluripotent stem cells (iPSCs) by reprogramming skin fibroblasts obtained from patients with ≥50 years of T1D with (+C) or without (-C) complications or healthy controls (n=6). Reprogramming efficiency was compromised in T1D+C (0.002%) compared to T1D-C (0.01%) or controls (0.02%) [p<0.001]. Furthermore, iPSCs from T1D+C demonstrated impaired in vitro and in vivo (post transplantation into mice) differentiation potential (10%), unlike controls (90%) or T1D-C (70%) [p<0.001] suggesting impaired regeneration/ cellular differentiation. To explore the molecular basis, we subjected the iPSCs to microarray gene expression and quantitative mass-spectrometry proteomics analyses. Intriguingly, phospho-histone2AX (pH2AX), a surrogate for DNA double strand breaks (DSBs), was up-regulated in T1D+C. Components of the DSB repair machinery were down-regulated and phosphorylation-dependent activation of downstream effectors, Chk1 and Chk2 was impaired (p<0.001). Further investigations revealed an increased expression of miR200 family of micro-RNAs in T1D+C (p<0.001). Indeed, over-expression of miR200a and/ or miR200b/c down-regulated ATM/ATR proteins, reduced pChk1 and pChk2 expression, increased pH2AX and cellular apoptosis. These changes were reversed by restoration of endogenous ATM/ATR proteins. This phenomenon was consistent in patient fibroblasts and in cell lines representing target cells in T1D complications (e.g. beta cells, kidney cells) suggesting clinical relevance. Our work highlights the regulation of DNA DSB repair pathway by miR200 as a novel mechanism underlying diabetic complications, alterations in which may enable better therapeutics to reduce the burden of T1D. Supported by: JDRF; NIH & For author disclosure information, see page 829. A424 Guided Audio Tour poster ADA-Funded Research GENETICS—TYPE 1 DIABETES & 1624-P 1626-P FOXP3 Mutations Causing Neonatal Diabetes Without Classic Features of IPEX Syndrome ANGELA M. HENSCHEL, SHUANG JIA, MARY KALDUNSKI, SCOTT PAVLETICH, JOHN CORBETT, MARTIN J. HESSNER, Milwaukee, WI JESSICA L. HWANG, HONGGANG YE, VERONICA P. PAZ, ASHLEY PASTORE, XIAOMING LIU, CRAIG L. HANIS, LOUIS H. PHILIPSON, SIRI ATMA W. GREELEY, Chicago, IL, Houston, TX Spontaneous T1D in lymphopenic BB DRlyp/lyp rats depends on Iddm1 (MHC class-II, RT1u/u) and Iddm2 (Gimap5-/-, resulting in regulatory T-cell (TREG) deficiency). BB DR+/+ littermates, wild-type for Gimap5, are not lymphopenic nor spontaneously diabetic but develop T1D upon TREGdepletion. Introgression of Iddm1 and Iddm2 onto the F344 rat genome is insufficient for T1D, supporting that BB rats possess additional susceptibility that is absent in the F344 strain. Unlike other rat strains, BB rat β-cells show evidence of duress by expressing the chemokine eotaxin after weaning but before insulitis. To identify genes/pathways that may contribute to isletspecific BB rat T1D susceptibility we used global gene expression profiling to longitudinally examine the islet transcriptome of DRlyp/lyp, DR+/+ and nondiabetic Iddm1/Iddm2 congenic F344 control rats during the DRlyp/lyp pre-onset period: days 20 (weaning), 30 (prior to histological detection of eotaxin expression), 40 (prior to insulitis) and 50 (early insulitis) (n= 6-10 rats/ cohort). Pathway analysis of transcripts longitudinally regulated in the DRlyp/ lyp and DR+/+ rats but not in the F344 control rats identified an increase in positive regulation of immune response and chemokine activity, consistent with a response to lipopolysaccharide and reports of gut hyperpermeability in BB rats. Upstream regulator analysis based on time-wise comparisons (| log2 ratio | > 0.5 for BB vs F344 control) identified increased transcript abundances related to NFkB activation (CXCL10, CXCL2, IRF1, HSPA9 and VCAM1) by day 40 in the DR+/+ (z-score 3.283; overlap p-value 1.62E-06). Upstream regulator analyses also showed several activated NFkB regulators (z-score > 2.0; p < 0.005) in day 30 DRlyp/lyp and day 40 DR+/+ islets including TNF, IL1 and CHUK. These data support the hypothesis that both BB sub strains possess an underlying islet-level susceptibility that, in the absence of immune regulation, results in progression to T1D. 0132SB01 0075JW01 c.1040G>A c.340C>T R347H R114W Previous reports Multiple None reports-variable phenotype Current age (yr) 19 31 Gestational age (wk) 42 40 Birth weight (gm) 3900 3930 Diabetes dx age (wk) 1.5 26.1 Diabetes treatment Insulin pump Glargine/lispro Last HbA1c (%) 9.3 7.8 Autoimmune/ Result not + anti-thyroid antibodies available FOXP3 mutation Supported by: NIH & 1625-P Encephalomyocarditis (EMC)-D Virus-Induced Diabetes in Tyk2 Gene Knockout Mice KEIICHIRO MINE, MIHO TESHIMA, YUJI KAI, KATSUYA KAI, KEN-ICHI IZUMI, HIRONORI KURISAKI, HITOSHI KATSUTA, SEIHO NAGAFUCHI, Fukuoka, Japan, Saga, Japan Type 1 diabetes mellitus results form the progressive loss of pancreatic β cells. The virus, as one of environmental factors, has long been considered to play a role in the development of type 1 DM. The D variant of encephalomyocarditis (EMC-D) virus induced susceptible strain of mice to induce type 1 diabetes, serving as an excellent animal model of virus-induced diabetes. We have already reported that innate immunity may play an important role in protection against EMC-D virus-induced diabetes. In the present study, we focused on tyrosine kinase 2 (Tyk2) gene which is an interferon receptor associated signaling molecule. We analyzed the role of Tyk2 gene in the pathogenic mechanism of EMC-D virus-induced diabetes by using Tyk2 gene knockout (KO) mice. Tyk2 gene KO C57BL/6J mice developed diabetes. These mice presented extensive destruction of pancreatic βcells and infiltrations of mononuclear leukocyte into pancreatic βcells were also observed. In order to examine whether Tyk2 gene expression was important in parenchymal or immune cells to protect against EMC-D virus-induced diabetes, we developed splenic chimera mice: lethally irradiated mice receiving spleen cells. Here, we have shown that Tyk2 gene expression was important in parenchymal cells, but not in spleen cells, to resist against EMC-D virus-induced diabetes. Furthermore, to evaluate Tyk2 gene expression in pancreatic βcells, we developed mice that Tyk2 gene was specifically expressed in pancreatic β cells: mouse-insulin-promoter-Tyk2 (MIP-Tyk2) transgenic mice. Consistently, Tyk2 KO mice crossed with Tyk2 transgenic mice that express Tyk2 gene specifically in pancreatic beta cells, prevented EMC-D virus-induced diabetes, without destruction of pancreatic β cells nor infiltrations of mononuclear leukocyte into pancreatic islets. These observations suggest that Tyk2 gene expressed in pancreatic β cells plays an important role to protect against EMC-D virus-induced diabetes in mice. Gastrointestinal No enteropathy Skin Other medical problems Mild eczema Short stature; frequent nighttime hypoglycemia associated with seizures Immunosuppression Never 0078NC01 c.1044+5G>A 0078NC04 c.1044+5G>A One report with classic IPEX 9 41 3520 104.5 (2.1 yrs) Insulin pump 7.9 + anti-islet cell - anti-thyroid - anti-adrenal - anti-enterocyte - TTG/endomysial 7 37.5 3400 26.7 Insulin pump 8.4 + anti-insulin + anti-parietal cell - anti-thyroid - anti-adrenal - anti-enterocyte - TTG Mild chronic Extreme FTT, weight at < No discomfort 5th percentile; EGD enteropathy result: inactive peptic duodenitis and inactive chronic gastritis; no apparent enteropathy Mild eczema Severe eczema, vitiligo Mild eczema Hypothyroidism Paralyzed diaphragm Vitamin B12 with temporary tracheo- deficiency stomy; multiple pneumonias and pump site infections, one time pyelonephritis Never Never Never Supported by: UC DRTC (P60 DK020595); JDRF (9-2008-177); NIH (UL1RR024999) Supported by: Ministry of Health, Labor and Welfare (Japan) ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A425 POSTERS Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare autoimmune disorder caused by mutations in FOXP3, a gene encoding a forkhead box transcription factor required for the function of CD4 + CD25 + regulatory T cells which regulate immunologic tolerance. In addition to neonatal diabetes (NDM), classic IPEX includes severe autoimmune enteropathy and eczema. Even with aggressive immunosuppressive treatment or stem cell transplant, death often occurs by 24 months of age from failure to thrive or sepsis. We describe the variable phenotypes of subjects unexpectedly found to have FOXP3 mutations within our Neonatal Diabetes Registry (https://monogenicdiabetes.uchicago.edu/ neonatal-registry/). Exome sequencing of 19 probands without a known cause for NDM revealed 3 different FOXP3 mutations in 4 male subjects in 3 families. One mutation is novel (R114W). Clinical information is shown in the table (0078NC01 and 0078NC04 are brothers). We conclude that mutations in FOXP3 are not uncommon in patients with NDM even when they lack other features of IPEX syndrome. Our prevalence is comparable to a previous report of FOXP3 mutations found in 6.7% of confirmed monogenic cases. The four cases we describe have only mild inconsistent IPEX-like features, are currently 7 to 31 years old and have never been treated with immunosuppressives. Mutations in FOXP3 should be considered in male patients with early onset diabetes with or without other features. Epidemiology/ Genetics & Biobreeding (BB) Rat Islets Exhibit Underlying Islet Dysfunction Independent of Insulitis and T1D Onset GENETICS—TYPE 1 DIABETES & 1629-P 1627-P Evidence of Stage- and Age-Related Heterogeneity With Non-HLA Single Nucleotide Polymorphisms (SNPs) and Risk of Islet Autoimmunity (IA) and Type 1 Diabetes (T1D)—The Diabetes Autoimmunity Study in the Young (DAISY) Evidence of a Preserved CRP Response to Acute Inflammation in HNF1A-MODY SAIMA A. MUGHAL, TIM J. JAMES, SUSAN BEATTY, MARK I. MCCARTHY, KATHARINE R. OWEN, Oxford, United Kingdom BRITTNI N. FREDERIKSEN, ANDREA K. STECK, MIRANDA KROEHL, MOLLY M. LAMB, RANDALL WONG, MARIAN J. REWERS, JILL M. NORRIS, Aurora, CO Previously, we had examined over 30 non-HLA SNPs in DAISY, and found SNPs in PTPN22, UBASH3A, INS and IFIHI to be associated with IA development and/or progression to T1D, two stages in T1D development. We now investigate 15 additional non-HLA T1D candidate SNPs. Of 1,622 non-Hispanic white DAISY children genotyped, 130 developed IA (defined as positive for GAD, insulin or IA-2 autoantibodies on two or more consecutive visits), and 44 IA positive children progressed to T1D. We conducted Cox regression analyses to examine risk of IA, and progression to T1D in IA positive children, and whether risk varies by age. C1QTNF6 (rs229541) predicted increased IA risk, and PRKCQ (rs947474) predicted decreased risk of progression to T1D in IA positive children. SNP (rs10517086) appears to exhibit an age-related effect on risk of IA, with increased risk in younger ages but not older ages (Age*SNP interaction p=0.003). SNP (rs10517086) was also associated with increased risk of progression to T1D in IA positive children. SNPs (rs2825932, rs9388489, rs1465788, rs2069762, rs4505848, rs12722563, rs7804356, rs7221109, rs2104286, rs6897932, rs3788013, and rs5979785) were not associated with IA or T1D development. This prospective investigation of T1D loci shows that some SNPs may exhibit stage- and age-related heterogeneity in the natural history of T1D. Association between non-HLA SNPs and risk of IA and progression to T1D in IA positive children SNP Minor MAF Risk of IA HR P value Progression to T1D HR P allele (95% CI) (95% CI) value rs229541 (C1QTNF6) A 0.44 1.52 (1.16, 1.98) 0.002 0.37 (0.17, 0.80) 0.01 rs947474 (PRKCQ) G 0.17 1.30 (0.88, 1.91) 0.19 0.37 (0.17, 0.80) 0.01 rs2104286 (IL2RA) C 0.27 0.85 (0.63, 1.16) 0.30 1.37 (0.80, 2.33) 0.25 rs6897932 (IL7R) T 0.28 0.89 (0.65, 1.21) 0.45 0.79 (0.52, 1.21) 0.28 rs3788013 (UBASH3A) A 0.44 1.24 (0.93, 1.66) 0.14 1.18 (0.78, 1.78) 0.43 rs10517086 A 0.30 1.00 (0.73, 1.35) 0.97 1.69 (1.03, 2.76) 0.04 *All SNPs adjusted for HLA-DR3/4,DQB1*0302 genotype and first degree relative with T1D and analyzed additively except PRKCQ, which was dichotomized for at least 1 minor allele. Table limited to SNP analysis models with p<0.30. POSTERS Epidemiology/ Genetics HNF1A regulates hepatic C-reactive protein (CRP) production and we reported that European subjects with HNF1A mutations (HNF1A-MODY) have low baseline levels of CRP. As HNF1A is part of the transcriptional complex involved in interleukin-6 stimulated CRP production during acute inflammation, we hypothesised that they would also have an attenuated CRP rise during an acute inflammatory stimulus. This could lead to impaired complement activation and macrophage function in HNF1A-MODY. HNF1A-MODY subjects with diabetes (n=7) and normoglycaemic BMI and gender-matched controls (n=9), received intravenous endotoxin (E. coli lipopolysaccharide: 2ng/kg). Serum CRP, white cell count (WCC) and erythrocyte sedimentation rate (ESR) were measured at baseline and 2, 4, 6, 24 hours and 8 days after endotoxin administration. CRP and WCC rose as expected in response to endotoxin in both groups (Figure 1) while no consistent response was seen with ESR. We found no difference in either the CRP levels or the WCC at any time point during the acute inflammatory response in subjects with HNF1A-MODY compared to controls (p=0.42 and 0.15 respectively by repeated measure analysis of variance). Peak mean CRP (HNF1A-MODY vs. controls) was 28.1 vs. 31.7 mg/L at 24hrs (p=0.45) and peak mean WCC was 11.2 vs. 9.5 at 6 hours (p=0.31). In conclusion, we demonstrate that HNF1A haploinsufficiency does not appear to impair CRP production during the response to a moderate acute inflammatory stimulus. Supported by: Oxfordshire Health Services Research Committee 1628-P Supported by: NIH (R01DK49654), (R01DK32493), (P30DK57516), (UL1RR025780) Confirmation that Dominant Inheritance of a GATA6 Mutation Causes Cardiac Defects, Dorsal Pancreatic Agenesis and Diabetes With Variable Expression 1630-P DAVID P. MACFARLANE, DAVID GOUDIE, JONATHAN BERG, ANDREW J. CASSIDY, JOANNE RAMSAY, ANNA M. CHOY, ALASDAIR MACKIE, EWAN R. PEARSON, Dundee, United Kingdom Longitudinal Change in Regional Brain Volumes in Early Wolfram Syndrome: A Preliminary Report De novo mutations in the transcription factor encoding GATA6 gene have recently been described as the commonest cause of pancreatic agenesis with insulin treated neonatal diabetes, and are commonly associated with congenital cardiac defects. More recently a Japanese family was found to have a dominantly inherited GATA6 mutation with variable expression of the clinical phenotype. Here we describe the case of an affected proband with a confirmed GATA6 mutation, with a number of family members displaying variable features of the GATA6 mutation syndrome. Following an atrial-septal defect (ASD) repair aged 35, our proband had 2 successful pregnancies complicated by gestational diabetes, and developed diabetes aged 42, rapidly progressing to insulin therapy. Both daughters (now aged 16 & 18) had congenital heart disease, both with a patent ductus arteriosus and ASDs, but have no signs of pancreatic endocrine or exocrine insufficiency. Imaging confirmed pancreatic hypoplasia (absent body and tail) in the proband and 1 daughter, with rotational abnormalities of the proximal small bowel also seen in the proband. DNA sequencing in the proband, and daughters revealed a GATA6 c.1620+5G>A mutation located in intron 6, predicted to reduce efficiency of the splice donor site. The proband’s parents have no similar clinical features, but a paternal aunt had suspected type 1 diabetes and 1 of the proband’s 5 siblings was diagnosed with suspected type 1 diabetes in his third decade. He has 4 live children, 2 with congenital cardiac abnormalities (pulmonary stenosis and VSD), suggesting that he may also have inherited the GATA6 mutation, although genetic studies are outstanding. In summary, we have described a new kindred with a dominantly inherited suspected pathogenic mutation in the GATA6 gene causing variable clinical features of congenital cardiac disease, pancreatic hypoplasia and diabetes presenting later in life. HEATHER M. LUGAR, JERREL RUTLIN, JONATHAN M. KOLLER, JOSHUA SHIMONY, TAMARA HERSHEY, THE WASHINGTON UNIVERSITY WOLFRAM STUDY GROUP, St. Louis, MO Wolfram syndrome (WFS) is a rare autosomal recessive disease with childhood onset insulin dependent diabetes, optic nerve atrophy, hearing loss, diabetes insipidus and neurodegeneration that results in death by middle adulthood. We previously determined that WFS is associated with reduced brainstem and cerebellar volumes even in the youngest patients with the mildest symptoms. However, little is known about the course of neurodegeneration in WFS, particularly at the early stages of the disease. We acquired structural magnetic resonance imaging on 14 relatively young WFS patients. Mean age at entry was 13.7 years (SD=5.6, range=5.9 to 25.8). Ten of these patients were scanned twice and 7 were scanned 3 times, at 1 year intervals. Brainstem, cerebellar gray and cerebellar white matter were measured using Freesurfer. No volumetric changes were seen after only 1 year, but a significant decrease in volume was seen over 2 years in cerebellar gray matter (p=.04), with marginal decreases in brainstem (p=.06) and cerebellar white matter (p=.09). Examination of a cross-sectional, convenience sample of healthy controls (n=53) and type 1 diabetics (n=26) suggested that a decrease in cerebellar gray matter volume is expected over this age range (r=-.40, p<.001). In contrast, brainstem and cerebellar white matter volumes tend to increase over this age range in non-WFS groups (both r=.22, p=.05), suggesting that the WFS patients diverge from a typical developmental trajectory in these regions. There was also a negative correlation between age at entry and percent change in brainstem volume over 2 years (rs=-.43, p=.05), indicating accelerated loss of brainstem volume & For author disclosure information, see page 829. A426 Guided Audio Tour poster ADA-Funded Research GENETICS—TYPE 2 DIABETES wide significance. The common lead SNPs are specific to one ancestry group, or are polymorphic across ethnicities with predominantly homogenous effects on T2D susceptibility. Whole exome sequencing of these individuals will allow evaluation of the role of rare genetic variation on T2D susceptibility within and between major ancestry groups. with age. Longitudinal follow-up of a larger WFS cohort and control groups is ongoing and will be critical for drawing stronger conclusions. However, preliminary results indicate that structural neuroimaging metrics have promise as potential biomarkers of neurodegeneration in early WFS. Supported by: Snow MIR; NIH (DK01674639), (DK064832); NCRR (10RR02298401A), (UL1RR024992), (HD070855) & 1631-P 1633-P Multiethnic Whole Exome Sequencing Identifies Low Frequency and Rare Coding Variants Associated With Glycemic Traits: Results from T2D-GENES Influence of Endogenous IL-27 on Human Monocytes ELIZABETH M. BRADSHAW, WASSIM ELYAMAN, MICHAEL FRANGIEH, ANNA TANG, ANGELINA BERNEIR, NIR HACOHEN, VIJAY K. KUCHROO, Boston, MA Supported by: BADERC; JDRF Supported by: NIDDK; NHGRI; NIH GENETICS—TYPE 2 DIABETES & Guided Audio Tour: Genetics of Type 2 Diabetes and Related Traits (Posters: 1632-P to 1639-P), see page 17. & VASILIKI LAGOU, REEDIK MAGI, LETIZIA MARULLO, KRISTA FISCHER, GUDMAR THORLEIFSSON, BEBEN BENYAMIN, MIKAEL AKERLUND, SYMEN LIGTHART, HARMEN H.M. DRAISMA, IDA SURAKKA, SARA HÄGG, JULIE DUMONT, ALINE MEIRHAEGHE, MARIKA KAAKINEN, MASSIMO MANGINO, JANINA S. RIED, ANUBHA MAHAJAN, MOMOKO HORIKOSHI, KONSTANTIN STRAUCH, SAMULI RIPATTI, ANDREW P. MORRIS, VALERIYA LYSSENKO, INGA PROKOPENKO, Oxford, United Kingdom, Tartu, Estonia, Reykjavik, Iceland, Queensland, Australia, Malmö, Sweden, Rotterdam, Netherlands, Amsterdam, Netherlands, Helsinki, Finland, Stockholm, Sweden, Lille, France, Oulu, Finland, London, United Kingdom, Neuherberg, Germany 1632-P Genome-Wide Association Study of 10,947 Type 2 Diabetes Cases and Controls from Five Ancestry Groups Provides Novel Insights into the Genetic Architecture of the Disease ANDREW P. MORRIS, XUELING SIM, PIERRE FONTANILLAS, T2D-GENES CONSORTIUM, Oxford, United Kingdom, Ann Arbor, MI, Cambridge, MA We undertook a genome-wide association study (GWAS) of type 2 diabetes (T2D) from five ancestry groups: African American (AA), East Asian (EA), European, Hispanic American and South Asian. We performed transethnic meta-analysis (MANTRA) of 5,464 T2D cases and 5,483 controls, imputed at up to 32.3 million variants from the 1000 Genomes Project (Phase I), providing near complete coverage of variation with minor allele frequency (MAF) ≥1% in each ancestry group. With these data, we aimed to: (i) identify novel T2D susceptibility loci; and (ii) provide insights into the genetic architecture of the disease. We identified 3 novel susceptibility loci at genome-wide significance, defined by log10 Bayes’ factor (BF) > 6, near PDGFRL (log10BF=6.43), CLDN10 (log10BF=6.37) and LEP (log10BF=6.36). The lead variant near PDGFRL is common (MAF≥5%) in all ancestry groups and demonstrates consistent odds ratios (OR) across ethnicities (fixed-effects OR=1.20 [1.13-1.28]). The lead variant near LEP is also common in all ancestry groups, but the allelic effect is heterogeneous between ethnicities (log10BF=5.07), and is specific to EA populations (MAF=10.5%, OR=1.85 [1.50-2.27]). At CLDN10, the lead variant is rare (MAF<1%) in EA, EU, HA and SA populations, so that the effect is AA-specific (MAF=8.7%, OR=1.98 [1.58-2.49]). Our results highlight the benefits of trans-ethnic GWAS meta-analysis for discovery and characterisation of T2D susceptibility loci. We identified no low-frequency variants (MAF<5%) at novel or established loci at genomeADA-Funded Research & 1634-P Large-Scale Multi-Phenotype Meta-Analysis Evaluates Pleiotropic Effects on Cardiometabolic Factors and Risk for Type 2 Diabetes (T2D) at FTO, FADS1 and GIPR Loci Cardiometabolic risk factors and T2D are correlated epidemiologically and share common genetic predisposition, as confirmed by single-trait genomewide association studies. Therefore, a large-scale multi-trait analysis can be a valuable tool to dissect independence of effects of a genetic variant on metabolic traits and disease risk, e.g. pleiotropy. We aimed to a) evaluate the multi-trait analysis method using FTO variant known to exert its action via body mass index (BMI) and b) explore multi-trait effects at FADS1 and GIPR. We implemented a method that utilizes multiple logistic regression with a genetic marker as the outcome and traits as explanatory variables. Multi-phenotype sets were analysed based on their differential availability in participating cohorts. Model selection was based on Bayesian Information Criterion scores summed across studies from derived model likelihoods. Analysis was performed in up to 167,984 European individuals from 25 studies within the ENGAGE consortium. Consistent with previous reports, the multitrait meta-analysis confirmed BMI as driving associations with other traits at FTO, suggesting absence of pleiotropy. Variants at FADS1 have an effect on lipids, fasting glucose and resting heart rate among others. At FADS1, the best models within multi-phenotype sets underscored independent effects for triglycerides and total cholesterol (TG/TC, PLRT =1.6x10 -78). Variants at GIPR For author disclosure information, see page 829. Guided Audio Tour poster A427 POSTERS Type 2 diabetes (T2D) is a worldwide health concern with a complex genetic basis. Common genetic variants (MAF>5%) in over 50 loci are associated with variation in levels of fasting glucose (FG) and insulin (FI). We tested the hypothesis that rare (MAF<0.5%) and low frequency (LF 0.5%<MAF<5%) variants contribute to variation in FG, FI, and A1C. Within T2D-GENES consortium, we analyzed whole exome sequences for 1943 subjects used as controls in studies on type 2 diabetes (T2D) of East Asian (EA, 547 from Korea, 450 from Singapore), South East Asian (SA, 577 Singapore), and European (EU, 369 Finland) origins. We performed singlevariant analysis using all cohorts combined and also each cohort separately. We also performed gene level burden tests, which aggregate evidence for association across rare and LF variants within each gene. We identified 1.8 million variants, 91% of which were rare, 5% were LF, and 4% were common. We found a genome-wide significant LF-rare variant associated with A1C in the G6PD gene from the combined sample analysis (rs72554665, p=1.8x10 -10, MAF 1.7% and 0.1% among EA and SA from Singapore, monomorphic for Korean EA and EU). Suggestive association was found between G6PD and FG (p=0.03). Burden tests on FG showed association with two novel genes POLR1B (p=8.1x10 -7) and IRF9 (p=1.8x10 -6). Whole exome sequencing identified rare and LF coding SNPs associated with A1C and FG in a large multiethnic sample. The variant rs72554665 is a mutation that causes G6PD deficiency and severe hemolytic anemia. Its association with A1C is likely to be secondary to altered red blood cell life span, but suggestive association with FG suggests involvement in glucose homeostasis. Variation at rs72554665 in G6PD is population specific. IRF9 is reported to be a key JAK-STAT pathway factor in eliciting the antiproliferative activity of IFN-alpha, but the mechanism linking it with glucose homeostasis remains to be elucidated. Epidemiology/ Genetics HAE KYUNG IM, T2D-GENES CONSORTIUM, Chicago, IL IL27 was recently identified as a genetic risk locus for type 1 diabetes, however how this locus influences susceptibility to type 1 diabetes is unknown. IL-27 is a pleiotropic cytokine that initially was described as being pro-inflammatory and an inducer of Th1 cells. More recently it has been described as an anti-inflammatory cytokine in that it suppresses proinflammatory T helper (Th)17 cells and induces anti-inflammatory T regulatory (Tr)1 cells. While the majority of studies are focused on the effects of IL-27 on T cells, antigen-presenting cells appear to express high levels of the IL27 receptor ex vivo, as well as be the major producers of it. We have found that monocytes, negatively isolated by MACS beads from healthy subjects, in the resting state are repressed by endogenous IL-27, in that the addition of a neutralizing antibody increases the production of pro-inflammatory cytokines (IL-6, IL-1b, TNF-a). We are pursuing a systems biology approach to determine which pathways are repressed by endogenous IL-27. While LPS activated monocytes produce more IL-27 than resting-state monocytes, they no longer respond to endogenous IL-27, presumably due to their rapid loss of surface IL-27 receptor upon activation. Interestingly, ex vivo monocytes from type 1 diabetic subjects produce more IL-27, consistent with the studies demonstrating that monocytes from type 1 diabetic subjects are in an activated state. We also observed that neutralizing endogenous IL-27 in monocyte-CD4+T cell co-cultures leads to the predicted increase in T cell IL17 production and decrease in IL-10 and IL-21 production. Interestingly, IL10 and IL21 are also in genetic loci associated with type 1 diabetes. IL-27 plays many roles in the immune system and understanding its primary contribution to type 1 diabetes susceptibility could lead to potential early intervention treatments. GENETICS—TYPE 2 DIABETES allele of the rs2074196 SNP, and stimulated the transcriptional activity of the artificial promoter including the rs2074196 SNP in allele-specific manner. These results suggested that the rs2074196 SNP modulate the affinity of the locus for KSBF5-7 and induce the subsequent change in gene expression, which would provide important clues for how the type 2 diabetes-associated SNPs within KCNQ1 gene promote the disease risk. are associated with BMI, T2D and 2 hour post load glucose and insulin. We were not able to detect pleiotropy at GIPR; however we could not rule it out due to a smaller number of individuals with 2-hour glucose measurements in the current study. The multi-trait method for dissecting genetic associations on cardiometabolic risk factors and T2D demonstrated that variants at FTO confirm BMI-mediated effects, while those at FADS1 exert pleiotropic effects influencing lipid metabolism, specifically TG and TC. & Supported by: European Network for Genetic and Genomic Epidemiology & 1635-P Silencing of the Type 2 Diabetes-Associated Gene ADCY5 Impairs Glucose-Stimulated Insulin Secretion from Human Islets ERIC R. GAMAZON, NANCY J. COX, SWAPAN K. DAS, Chicago, IL, Winston-Salem, NC POSTERS GUY A. RUTTER, RYAN MITCHELL, MARCO BUGLIANI, PIERO MARCHETTI, DOMENICO BOSCO, PAUL R. JOHNSON, STEPHEN HUGHES, WEN-HONG LI, DALIANG LI, DAVID J. HODSON, London, United Kingdom, Pisa, Italy, Geneva, Switzerland, Oxford, United Kingdom, Dallas, TX Epidemiology/ Genetics 1637-P Adipose eQTLs Identify Genetic Basis of Metabolic Traits and Insulin Sensitivity Associated SNPs With Predictive Effect on β Cell Function Genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with obesity, type 2 diabetes (T2D) and related metabolic traits (MT). Here, we analyzed genome-wide adipose expression data (Illumina Human HT-12 V4 chip) from a cohort of 136 metabolically well-characterized non-diabetic subjects (age 19-59 yrs, BMI 19-42, SI 0.66-13.02, and Caucasian/African American 99/37). We found that physiological variables and hidden confounders have significant effects on gene expression and conditioning on them substantially improves power to identify expression quantitative trait loci (eQTLs). We conducted an eQTL study of SNPs (n=487, Illumina-HumanExome-12v1.1 chip) reproducibly associated with BMI, T2D, and MT from the comprehensive NHGRI catalogue of GWAS findings. BMI, T2D, and MT showed trait-specific enrichment for adipose eQTLs relative to genomic background whereas no adipose eQTL enrichment was observed among (as control) the subset of SNPs associated with neurodegenerative disorders (schizophrenia and bipolar). We identified hundreds of eQTLs among the MT associated SNPs, including cis-eQTLs for ATP13A1 (triglyceride associated SNP rs17216525, p = 1.16X10 -14), CPEB4 (WHR associated SNP rs6861681, p = 3.27 X10 -11) and ADIPOQ (adiponectin associated SNP rs17366568, p= 8.17X 10 -11). Using MAGIC consortium data, we observed a significant excess (p<0.001) of β cell function (HOMA-B) associated SNPs among top insulin resistance (IR, using HOMA-IR) associated SNPs (p<1X10 -4). Remarkably, IR associated eQTLs showed a more dramatic enrichment for SNPs predictive of β cell function relative to other IR associated SNPs. These findings suggest that eQTL mapping using detailed physiological phenotypes substantially enhances power to identify the genetic basis of metabolic traits as well as IR associated SNPs, in a peripheral tissue, with significant predictive effect on β cell function. Genome-wide association studies have recently identified a single nucleotide polymorphism (SNP), rs2877716, which increases the risk of elevated fasting blood glucose and type 2 diabetes. The SNP is located on chromosome 3 in intron 1 of the ADCY5 gene, encoding the cAMP-generating enzyme adenyl cyclase 5. Parallel sequencing has shown that ADCY5 mRNA levels occupy the top quintile in purified human islets, whilst lower levels are expressed in mouse islets. We therefore sought to investigate the impact of silencing this gene on beta cell function using human islets. To monitor the cell dynamics underlying insulin secretion within intact human islets, intracellular free Ca2+ ([Ca2+]i) was imaged using fluo2 whilst the cell surface-bound Zn2+ probe, ZIMIR, monitored hormone release. Genesilencing was achieved using lentivirus particles harbouring shRNA against ADCY5 or scrambled control (Con). Incubation with lentivirus for 72 h was sufficient to silence ADCY5 mRNA expression by ~90% in dissociated islets and ~30% in intact islets. ADCY5 silencing dramatically (63.7 ± 3.0%; P<0.01) suppressed glucose- (11 vs 3 mM) stimulated rises in [Ca2+]i and mildly (26.4 ± 2.7%) reduced coordinated cell activity (P<0.05, n = 9 recordings). Apparent insulin release in the continued presence of the sugar was also lowered by ADCY5 silencing (64.2 ± 1.7%; P<0.01) (n = 5 recordings). These actions were not due to cAMP-independent effects on ATP-sensitive K+- or voltage-gated Ca2+-channels, as silencing did not alter Ca2+ rises induced by KCl. Paradoxically, ADCY5 knockdown subtly but significantly enhanced the amplitude and AUC of GLP-1-evoked increases in [Ca2+]i (P<0.01). In summary, ADCY5 potentiates glucose- but may restrain incretinstimulated insulin secretion. These results are consistent with the observation that carriers of the rs2877716 variant of ADCY5 present with elevated fasting glucose, but a normal insulinogenic index 2 hr post-oral glucose load. Supported by: NIH (DK039311) & 1638-P Parent-of-Origin Effect of GRB10 Variant on Glucose Metabolism and Islet Function in Man Supported by: Diabetes UK; Wellcome Trust (MRCEUFP7); The Royal Society MASAKI HIRAMOTO, HARUHIDE UDAGAWA, ATSUSHI WATANABE, MIHO KAWAGUCHI, WATARU NISHIMURA, TAKAO NAMMO, KAZUKI YASUDA, Tokyo, Japan, Obu, Japan WENNY POON, INGA PROKOPENKO, REEDIK MAGI, ALBERT SALEHI, PETER ALMGREN, RASHMI PRASAD, B. PETER OSMARK, NILS WIERUP, NABILA BOUATIA-NAJI, CHARLOTTE LING, PETER KOVACS, ERIK INGELSSON, MARK MCCARTHY, ALAN SHULDINER, KRISTI SILVER, MARKKU LAAKSO, LEIF GROOP, VALERIYA LYSSENKO, MAGIC INVESTIGATORS, Malmö, Sweden, London, United Kingdom, Oxford, United Kingdom, Paris, France, Leipzig, Germany, Uppsala, Sweden, Baltimore, MD, Kuopio, Finland Genome-wide association studies have identified a lot of SNPs that are associated with type 2 diabetes. However, because the most of these SNPs are located in non-coding regions of the genome, the mechanism by which they promote disease risk have remained elusive. Type 2 diabetes-associated SNPs identified in KCNQ1 gene are also located in intron 15 of KCNQ1, a gene that encodes the alpha-subunit of the voltage-gated potassium channel. In this study, we tried to identify the proteins that bind this locus in allelespecific manner, and to verify the relationship between the functions of these proteins and the risk of type 2 diabetes. We first prepared 2 types of beads, that is, risk allele beads and non-risk allele beads by immobilizing each allelic DNA onto magnetic nanobeads. Using these beads, we purified DNA-binding proteins from nuclear extract of INS-1 pancreatic beta-cell line and analyzed the proteins by SDS-PAGE. Comparing the bound proteins between using 2 types of beads, we picked up the differentially bound proteins (KSBFs) and identified the proteins using mass spectrometry analysis. We next confirmed the DNA-binding activities of KSBFs in vitro using recombinant proteins and in cell lines using chromatin immunoprecipitation assay. We further examined the transcriptional activities of KSBFs using luciferase reporter assay. We found that the affinities of several proteins for the examined SNPs (rs2074196, rs2237892, rs2237895, and rs2237897) within KCNQ1 gene were different between the alleles. KSBF5-7 specifically bound the non-risk Despite that many identified type 2 diabetes-associated genetic variants seem to influence β-cell function, no large-scale studies to date have evaluated the extent to which common genetic variants influence dynamic measures of insulin secretion. In the Meta-Analyses for Glucose- and Insulin-related traits Consortium (MAGIC), we conducted a GWAS metaanalysis for dynamic measures of insulin response to glucose during OGTT. The combined discovery and replication analyses in up to 26,037 nondiabetic individuals identified a variant in the growth factor receptor-bound protein 10 (GRB10) gene (rs933360) to be associated with reduced glucosestimulated insulin secretion (GSIS) at 30 min at genome-wide significance level (β=-0.051, p=3.14×10 -09). Paradoxically, the insulin-reducing A-allele was also associated with reduced fasting glucose levels (N=23,208, β=0.016, p=0.007). GRB10 is imprinted in a parent-of-origin manner in different tissues. We examined the effect of rs933360 on GSIS in 2,000 non-diabetic unique individuals from 2,289 parents-offspring trios from Finland, Sweden and USA. We observed that maternally transmitted A-allele was associated with reduced GSIS (5 out of 8 indices: β=-0.127--0.095, p=0.005-0.016). No effect was observed for paternally transmitted A-allele on insulin secretion. Surprisingly, maternally transmitted A-allele was associated with reduced glucose levels (β=-0.139, p=0.001). In contrast, paternally transmitted A-allele was associated with elevated glucose levels (β=0.102, p=0.002). Disruption of GRB10 through knock-down (KD) in human pancreatic islets & 1636-P Type 2 Diabetes-Associated SNPs Within KCNQ1 Gene Modulate the Affinity of the Locus for DNA-Binding Factors & For author disclosure information, see page 829. A428 Guided Audio Tour poster ADA-Funded Research GENETICS—TYPE 2 DIABETES resulted in reduced glucagon secretion. The strong effect of GRB10 KD may explain the paradoxical reduction of glucose values despite a decrease in insulin secretion. Taken together, these data provide new insights into the mechanisms by which GRB10 influences glucose metabolism, and the potential targeting of GRB10 as a mean to lower glucose without influencing insulin secretion. & 1639-P 1641-P Variation in MODY Genes Observed in Whole Exome Sequence Data from 10,000 Individuals: T2D-GENES Consortium Genome-Wide Association Analysis Identifies Variants Associated With Non-Alcoholic Fatty Liver Disease in Koreans HEATHER M. HIGHLAND, PIERRE FONTANILLAS, GRAEME I. BELL, NANCY J. COX, CRAIG L. HANIS, T2D-GENES CONSORTIUM, Houston, TX, Cambridge, MA, Chicago, IL JAE HEE AHN, JI HEE YU, CHAI RYOUNG EUN, SEUNG KU LEE, HO CHEOL HONG, HAE YOON CHOI, YOON JUNG KIM, NAM HOON KIM, HYE JIN YOO, JI A. SEO, SIN GON KIM, KYUNG MOOK CHOI, SEI HYUN BAIK, DONG SEOP CHOI, CHOL SHIN, NAN HEE KIM, Seoul, Republic of Korea Maturity onset diabetes of the young (MODY) is often misdiagnosed as type 2 diabetes (T2D) and approximately 1-2% of individuals diagnosed with T2D may have MODY. The most common causes of MODY in Europeans are heterozygous mutations in HNF1A, GCK, HNF4A, and HNF1B. We are systematically documenting the array of variation seen in these and other monogenic diabetes genes in 5000 individuals diagnosed with T2D and 5000 controls from 5 ancestry groups that have undergone deep coverage whole exome sequencing as part of the T2D-GENES Consortium. The array of variation seen in these genes in the first 5328 sequenced individuals (2755 controls and 2572 cases) is not significantly different in cases and controls as expected based on ascertainment (Table 1). Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. Ethnicity and genetic factors may influence on the incidence and severity of NAFLD. This study was aimed to identify genetic variants associated with NAFLD by genome-wide association study (GWAS) in Korean population. In 2,269 samples from the population-based cohort, the Korean Genome Epidemiology Study, SNP markers with call rate (<95%), low MAF (<0.01) and Hardy-Weinberg equilibrium (P < 1x10 -6) were excluded, leaving a total of 316,078 markers to be examined. Using unenhanced CT, the liver attenuation index (LAI) was calculated. NAFLD was defined by LAI <5 HU. SNPs in PNPLA3-SAMM50 gene (rs12483959, rs2076211, rs2281135, rs2073081, rs1883350, rs2143571, rs2281298, rs16991236) in chromosome 22, and in NRBF2-JMJD1C gene (rs12416113, rs9414780, rs9629895, rs907, rs10761745) in chromosome 10 were significantly associated with LAI after adjusting for age, sex, and body mass index (p value 3*10 -6~7.8*10 -15). The metabolic risk factors were not different according to haplotypes from PNPLA3. In the logistic regression model, odds ratio for NAFLD in the lowLAI-haplotype group from PNPLA3 gene was increased compared to the high-LAI-haplotype group after adjusting for metabolic risk factors. These associations were seen consistently, regardless of obesity status or liver function test. The log likelihood ratio test showed that the model with PNPLA3 haplotype and metabolic risk factors fitted better than that with metabolic factors only (p <0.001). In the imputation analysis, rs738409, the known functional SNP were in linkage disequilibrium with several SNPs found in the present this study. We identified several genetic variants in PNPLA3-SAMM50, NRBF2JMJD1c genes associated with NAFLD in GWAS. These findings suggest that several genetic variants may confer increased susceptibility to NAFLD regardless of obesity and conventional metabolic risk factors in Koreans. Table 1. Number of variants with MAF<0.005 observed split by effect on protein sequence genes nonsense and nonsynony- nonsynonymous non-damagsynonymous mous damaging ing # in cases/ # variants # in cases/ # variants # in cases/ # variants # in controls # in controls # in controls HNF1A 30/25 22 13/20 8 138/111 39 GCK 7/3 6 3/1 4 75/91 23 HNF4A 7/2 5 23/21 19 78/75 29 HNF1B 4/3 12 4/3 5 47/37 17 Within each gene, we tested the combined effect of the rare damaging variants using SKAT. After correcting for multiple testing, this revealed no genome-wide significant association with T2D in any of these genes with the smallest being p=0.012 in HNF1A. However, sequencing demonstrates that a wide array of variation is apparently well tolerated in MODY genes, and that rare mutations in MODY genes are not likely to be a frequent cause of T2D. We are undertaking parallel analyses for other monogenic diabetes genes, including: INS, KCNJ11, ABCC8, PAX4, NEUROD1, FOXP3, and EIF2AK3. Cataloging the array of coding variation this large multiethnic sample provides insight into the biological relationship of these genes to T2D. 1642-P Identification of a Candidate Gene for Type 2 Diabetes using Outbred Rats LEAH C. SOLBERG WOODS, KATIE HOLL, SHIRNG-WERN TSAIH, SHUANG JIA, MARY KALDUNKSI, MICHAEL TSCHANNEN, JAIME WENDT ANDRAE, RAYMOND HOFFMANN, PIPPA SIMPSON, HOWARD JACOB, MARTIN HESSNER, Milwaukee, WI 1640-P Genome-Wide Association Studies (GWAS) Meta-Analyses for A1c Levels in European and African American Ancestry Samples Reveal Novel Genetic Risk Variants Despite the success of human genome wide association studies (GWAS), much of the heritable variance for type 2 diabetes remains unknown. Outbred animals such as heterogeneous stocks (HS) allow for rapid fine-mapping of quantitative trait loci (QTL), and thus offer a complementary approach to identify genes involved in complex traits. Our laboratory has used HS rats to investigate a 60 Mb region on rat chromosome 1 that has previously been implicated in glucose tolerance. We narrowed this region to a 3.1 Mb QTL that maps fasting glucose and glucose tolerance and which sits within a 7.1 Mb QTL for fasting insulin and insulin resistance (1, 2). We hypothesized that expression and sequence analysis would enable us to identify a novel candidate gene within this region. Using the Affymetrix 230_2 array, we measured expression levels in liver of HS rats that differed in response to a glucose tolerance test. We identified one gene within this region, two pore channel 2 (Tpcn2), that was differentially expressed between HS rats with normal glucose and those with glucose intolerance and that mapped as a cis-acting expression QTL. We then used sequence information from the founder strains to identify a non-synonymous coding variant within this gene. We found that this variant was associated with a 6-fold decrease in expression levels as well as significantly increased fasting glucose and insulin levels. Using data from human consortiums, DIAGRAM and MAGIC, we found that variants within Tpcn2 are significantly associated with increased fasting insulin levels in humans, indicating this gene may play a role in human diabetes. Tpcn2 is a lysosomal channel involved in mediating MARIE-FRANCE HIVERT, ELEANOR WHEELER, CHING-TI LIU, ON BEHALF OF MAGIC AND AAGILE, Sherbrooke, QC, Canada, Cambridge, United Kingdom, Boston, MA A1c is now recommended for type 2 diabetes (T2D) diagnosis. The MetaAnalyses of Glucose and Insulin-related traits Consortium (MAGIC) previously undertook a GWAS meta-analysis of A1c levels in up to 45,000 non-diabetic European individuals and revealed 10 loci (P<5x10-8). MAGIC has now performed an updated meta-analysis in up to 132,914 European individuals. In parallel, the African American Glucose and Insulin Genetic Epidemiology (AAGILE) Consortium has performed a meta-analysis of GWAS for A1C in up to 6845 non-diabetic individuals from 7 cohorts. Samples were genotyped using standard GWAS platforms or the Metabochip. Variants were excluded if minor allele frequency (MAF)<0.01, HWE<10-4, call rate<0.95, or failed imputation. The European results confirm all 10 previously identified MAGIC signals and identify 34 additional loci including some previously found to be associated with red blood cell traits (eg. CTD1, P=1.2x10-27), glycemia (eg. SLC2A2, P=1.9x10-11) or type 2 diabetes (eg. SLC30A8, P=1.6x10-18). In AAGILE, a missense variation in G6PD (Val ==>Met) previously associated with glucose-6-phosphatase dehydrogenase deficiency was strongly associated with lower A1c levels (P=6.8x10-122) in line with higher red cell turnover. This variant is monomorphic in populations of European descent but common in African descent populations (YRI hapmap: MAF=0.22). Another ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A429 POSTERS Supported by: VR; ALF; Novo Nordisk Foundation; ERC; NIH Epidemiology/ Genetics suggestive genome-wide significant locus includes SNPs in/near EPS15L1/ KLF2 (P=3.8x10-8). Current analyses combining European and African descent samples using Meta-ANalysis of Transethnic Association Studies (MANTRA) software are underway to increase power and to improve the resolution of fine-mapping of causal variants by leveraging differences in local linkage disequilibrium structure between ethnic groups. Our findings might influence the use of A1c for T2D diagnosis in specific ethnic backgrounds. GENETICS—TYPE 2 DIABETES and subsequent genotype-phenotype correlation can be applied to identify new T2D relevant genes and quantitative trait associations. calcium release. To date, however, there is no known role for Tpcn2 in regulating fasting glucose or insulin levels in the liver. Current work in the laboratory is investigating the hypothesis that Tpcn2 is the causative gene in this locus. 1. Solberg Woods LC, et al., Physiol Genomics 41: 102-108, 2010. 2. Solberg Woods LC, et al., Physiol Genomics 44: 1013-1026, 2012. 1645-P Gene Expression and Metformin Efficacy in Type 2 Diabetes (T2D) SABRINA PRUDENTE, ANDREA MASOTTI, MASSIMILIANO COPETTI, NUNZIA CAPORARELLO, VITTORIA PROTO, LETIZIA DA SACCO, ELEONORA MORINI, LUANA MERCURI, DIEGO BAILETTI, ANTONIO PALENA, ROBERTO BARATTA, SALVATORE DE COSMO, FABIO PELLEGRINI, ORNELLA LUDOVICO, LUCIA FRITTITTA, VINCENZO TRISCHITTA, San Giovanni Rotondo, Italy, Rome, Italy, Catania, Italy Supported by: AHW (5520137); CRIPIR (2206339) 1643-P Reduction of Relative Hyperglucagonemia by Leptin Efficiently Controls Hyperglycemia in the Akita Mouse Though metformin is the “first choice” oral hypoglycemic agent (OHA) in patients with T2D, its exact mechanism of action on glycemic control is only partially known. We hypothesized that investigating mRNA expression profiles could help address this issue. Accordingly, we measured mRNAs levels in peripheral white blood cells (PWBC) from 60 T2D patients at baseline and after 3-month metformin treatment (with all previous OHA being discontinued for 5 days before baseline). Whole gene expression was evaluated by using the Human Gene 1.0 ST Arrays (Affymetrix) interrogating 28,869 genes. Bioinformatic analysis was performed using R Bioconductor and other home-made scripts. DAVID and GO databases were employed to obtain functional classifications. Clinical data. Three-month metformin therapy was effective in ameliorating BMI, fasting glucose, HOMA-IR index and HDL-cholesterol (p< 0.01 for all). Gene expression data. i) After metformin treatment, 1,763 genes were differentially expressed as compared to baseline (FDR<0.01). Bioinformatic analysis by functional classification showed that these genes belonged to several pathways among which only one, the spliceosome pathway, remained significantly associated after adjusting for multiple comparisons (p=1.10 -4). In addition, metformin efficacy (% decrease of baseline glycemia) was directly correlated with average down-regulation of genes belonging to the spliceosome pathway (r=0.42, p<0.001). ii) Baseline expression of 1,435 genes was correlated to metformin efficacy; after multiple comparison adjustment, only the spliceosome pathway remained significantly correlated to it (p=7.10 -12). At multivariate analysis, baseline expression level of spliceosome genes accounted for 57% variability of metformin efficacy. In conclusion, the spliceosome pathway seems to be involved in metformin efficacy. This finding paves the way for a better understanding of metformin mechanisms of action and efficacy. POSTERS Epidemiology/ Genetics CARLO COLOMBO, FABRIZIO BARBETTI, Rome, Italy Heterozygous, gain-of-function mutations of the insulin gene that cause insulin misfolding, trapping of insulin in the endoplasmic reticulum (ER), ER-stress and beta cell apoptosis lead to insulin deficit and neonatal diabetes (PNDM) in men. Two mouse models carry Ins2 gene mutations with proteotoxic effect: the Akita mouse (Ins2/C96Y) and the Munich mouse (Ins2/C95S). However, natural history of diabetes of Akita and Munich mouse differs from that of patients with PNDM associated with proteotoxic INS gene mutations: while in the latter diabetic ketoacidosis (DKA) is a frequent mode of presentation and C-peptide declines over time to undetectable levels in most patients, both Akita and Munich mouse survive through adult life after diabetes onset. This is in contrast with mouse models of absolute insulin deficiency like Ins1/Ins2 double knock out, that die with DKA 2 days after birth. We measured total plasma insulin in the Akita and wild type mice of 2,3,4 and 7 weeks of age and found that they were identical. Interestingly, C-peptide 2 (that reflects Ins2 secretion) measured from 2 to 25 weeks from birth was about 50% lower in Akita than wt mice (p<0.05, by T-test) while C-peptide 1 level was normal. In contrast, plasma glucagon was higher in the diabetic, 7-week old Akita mice than wt mice (97 vs 5 pg/ml, p<0.005). We applied 3 treatments to Akita mice. A single dose of 10 nmol/kg of exendin-4 to 3-week old Akita did not modify the course of diabetes. Insulin pellets implanted at 18, 25 and 32 days of life kept plasma glucose in the normal range until the end of observation period (42 d of life). Leptin, delivered by osmotic pump (6 mg/d) in 3-week old Akita, kept plasma glucose in the low-normal range for the entire observation period (32 d of life), while glucagon was suppressed (38 pg/ml on leptin, vs 123 pg/ml no leptin, p<0.001). We conclude that hyperglucagonemia, likely due to the decreased inhibitory tone on alpha cells by beta cells, is a main driver of hyperglycemia in the Akita mouse. 1644-P 1646-P High Throughput Functional Analysis of Coding Variants in PPARG Identifies Novel Loss-of-Function Alleles that Associate With Diabetes Risk and Systolic Blood Pressure Knowledge and Attitudes Towards Clinical Genomic Research among Hispanics Affected by Type 2 Diabetes AMIT MAJITHIA, JASON FLANNICK, DAVID ALTSHULER, JOHN R.B. PERRY, GOT2D CONSORTIUM, Boston, MA, Exeter, United Kingdom LILIANA URIBE-BRUCE, ISABEL GARCIA, LINDA GALLO, JILL WAALEN, JOHANNA EUYOQUE, PATRICIA GONZALEZ, ADDIE FORTMANN, JAMES SCHULTZ, MONICA RUIZ, ATHENA PHILIS-TSIMIKAS, San Diego, CA, La Jolla, CA Genetic variants identified in genome scale sequencing of large type 2 diabetes (T2D) case/control cohorts potentially enable discovery of new genes underlying T2D pathogenesis. Identifying a few biologically functional variants among many neutral variants is a key challenge. Model systems that allow rapid assessment of variant function in disease-relevant bioassays are needed. We have developed an experimental platform for the rapid and parallel introduction of candidate mutations into human SGBS pre-adipocytes that can be flexibly combined with a variety of phenotypic assays. In this work, we combine high content microscopy and automated image analysis to create a high throughput, quantitative adipocyte differentiation assay. We validate the performance of our assay by accurately identifying previously known gain and loss-of-function (LOF) mutations in PPARG, a master regulator of adipogenesis implicated in insulin resistance. We then apply our platform to functionally characterize 10 novel, nonsynonymous variants in PPARG found from sequencing 1403 T2D cases and 1331 matched controls and identify 6 new LOF variants spanning both the DNA and ligand-binding domains. We show that LOF variants in PPARG cluster in T2D cases (estimated odds ratio 3.32, p=.006, N=7), whereas non-LOF variants are more evenly distributed (estimated OR=1.87, N=4). We perform genotype-phenotype correlations with this set of biologically functional PPARG variants for blood pressure, BMI, waist-hip-ratio, and serum triglycerides; variants that decrease PPARG function in our assay inversely correlate with systolic blood pressure (r^2=-0.75 p=0.03). Our strategy of variant discovery, high-throughput experimental characterization, The discovery of more than 60 genetic risk variants for Type 2 Diabetes (T2D) brings the promise of personalized medicine closer to the clinic, but populations at disproportionately higher risk for T2D, such as Hispanics, have been underrepresented in these studies. As part of an effort to foster participation of underrepresented groups in genomic research, a culturallytailored community survey assessing knowledge of and attitudes towards clinical genomic research was developed and administered to Hispanics with T2D who attended federally qualified community health centers in Southern California. Basic genetic knowledge evaluated included: genes influencing disease individually and in human groups, DNA biobanks and clinical use of genetic information. Attitude items included: interest in genetic research, disease risk prediction and privacy concerns. IRB approval was obtained. 145 Hispanics completed the survey; 49% reported education up to middle school and 91% chose to answer in Spanish. Mean knowledge score was 7 out of possible 12. Lower knowledge scores were associated with lower levels of education (p=0.007) and lower (USA) acculturation (p=0.006) (ANOVA). Mean positive attitude score was 6 out of 9 possible. Higher positive attitudes towards genomic research were associated with higher education (p<0.001) and higher acculturation (p=0.004). Age, gender, income and religiosity were not significantly associated with knowledge or attitudes in this community. 93% of participants stated that they would participate in genomic research for altruistic reasons. We conclude that there are gaps in knowledge about genomic research among medically underserved Hispanics, which calls for tailored education efforts to foster informed participation of this underrepresented group in T2D & For author disclosure information, see page 829. A430 Guided Audio Tour poster ADA-Funded Research GENETICS—TYPE 2 DIABETES genomic research. This group expresses positive attitudes towards clinical genomic applications and interest in participating in genomic research to help future generations. 1649-P Investigation of Diabetes and Related Quantitative Trait Loci in GWAS for Insulin Sensitivity and Insulin Clearance Supported by: NIH (5KL2-RR025773-04) The GUARDIAN Consortium (Genetics Underlying Diabetes in Hispanics) seeks to identify genetic loci for insulin sensitivity and insulin clearance (IC) in 7 Hispanic cohorts (BetaGene, IRAS, IRAS Family, TRIPOD, MACAD, NIDDM-Athero, HTN-IR), totaling 4139 non-diabetic individuals in 1875 pedigrees. Insulin sensitivity (SI) and IC were measured by FSIGT with minimal model analysis in the first 4 cohorts. Insulin sensitivity (M/I) and IC were measured by euglycemic clamp in the latter 3. GWAS (Illumina Omni Express) has been completed; meta-analysis (adjusted by age and sex) was used to combine the IC results and the SI plus M/I results across cohorts. Herein, we examined the top loci (P<10 -3) for IC and SI+M/I for ~100 previously identified GWAS loci for T2D and related quantitative traits (fasting glucose, fasting insulin, 2-hr glucose, HbA1c, adiponectin). Given that the latter loci were largely discovered in non-Hispanic cohorts, we searched by region rather by SNP. For index SNPs within a gene, we used a gene +/- 100 kb window. For loci outside of genes, we used SNP +/- 200 kb. 12 SNPs in 4 loci were associated with IC: 5 SNPs in PTPRD, 4 SNPs in CDKN2A/2B, 2 SNPs in CDKAL1 (T2D loci), and 1 SNP in CITED2 (adiponectin locus). 6 SNPs in 5 loci were associated with SI+M/I: 2 in PTPRD, 1 in JAZF1, 1 in CHCHD9 (T2D loci), 1 in PDGFC (fasting insulin locus), and 1 in CDH13 (adiponectin locus). None of these were the index SNP found in the prior GWAS for these traits. The PTPRD locus is of interest, as one SNP (rs7851513) was significantly associated with both IC (P=2.7x10 -5) and SI+M/I (P=8.6x10 -4). These results illustrate that a subset of loci identified for T2D and related traits (largely in Europeans and East Asians) are also among the top signals in a GWAS meta-analysis for physiologically measured insulin sensitivity and clearance in Hispanics. Characterizing the function of these loci in Hispanics is the first step in elucidating the genetic architecture of T2D in this high risk ethnic group. MARYSA LEYA, LOREN L. ARMSTRONG, DOUGLAS A. SCHEFTNER, WILLIAM L. LOWE, M. GEOFFREY HAYES, LYNN P. LOWE, BOYD METZGER, ALAN R. DYER, RACHEL LOWN-HECHT, Chicago, IL Defining the genetic basis for gestational diabetes mellitus (GDM) may not only provide an understanding of its underlying pathogenesis, but also help determine a woman’s risk for GDM. Using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, we hypothesized that type 2 diabetes mellitus (T2DM) susceptibility and plasma glucose genes are associated with an increased risk of GDM. To address this hypothesis, we used genome-wide SNP data and phenotype data collected from four ancestry groups (European, Afro-Caribbean, Hispanic, and Thai) who participated in the HAPO Study (n=4516). Genotypes for SNPs spanning 97 genes associated with T2DM susceptibility or plasma glucose levels in nonpregnant adults were tested for association with GDM. GDM was defined using the new International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria and determined using maternal oral glucose tolerance test results at ~28 weeks gestation among HAPO participants. In addition to cohort-specific analyses, a meta-analysis across all four ancestry groups was also performed. Fifteen genes demonstrated association (p < 10-3) with GDM in the meta-analysis. These genes include: RYR2 (rs3766878), SIX3/2 (rs2917764, rs2922016), PPARG (rs1151999), PDGFC (rs17035317), RAI14 (rs368823), JAZF1 (rs6968494), CAMK1D (rs4364954), GALNTL4 (rs4444072), CENTD2 (rs12808507), MTNR1B (rs10830963), IGF1 (rs7971494), PRC1 (rs11853073), WWOX (rs9319517), CMIP (rs4889360), and BCL2 (rs4987864). While the SNPs identified in the meta-analysis did not necessarily reach significance within each cohort, when considered across all ancestry groups the P-value met the designated threshold for significance. These data suggest that there are similarities between the genetic underpinnings of GDM, as defined using the newly created IADPSG criteria, and T2DM susceptibility and plasma glucose levels. 1650-P Expression Analyses Suggest Self-Regulation of TCF7L2 Across Type 2 Diabetes Associated Variant rs7903146 1648-P QIANGHUA XIA, SANDRA DELIARD, MATTHEW E. JOHNSON, STRUAN F.A. GRANT, Philadelphia, PA Epigenetics of Fasting Insulin and Glucose Concentrations BERTHA HIDALGO, MARGUERITE RYAN IRVIN, JIN SHA, EDMOND K. KABAGAMBE, DEGUI ZHI, STELLA ASLIBEKYAN, DEVIN ABSHER, HEMANT TIWARI, DONNA K. ARNETT, Birmingham, AL, Nashville, TN, Huntsville, AL Variation at the TCF7L2 locus have been established to be strongly and robustly associated with type 2 diabetes (T2D). However, the mechanism of action by which this risk is conferred has still to be elucidated. Interestingly, the key 8q24 locus found to be the most strongly associated genomic region with a number of cancers through GWAS has been shown to contribute to the disease pathogenesis through mutation of an upstream TCF7L2-binding element driving the transcription of the MYC gene. As such, the fact that TCF7L2 regulates the key cancer locus poses the question: does TCF7L2 also regulate the key T2D locus, i.e. itself, through a feedback loop? Indeed, our previous results from ChIP-seq experiments identified several TCF7L2 binding sites within the gene itself, particularly in intron 3 where the genetic association with T2D has been localized to. Furthermore, our initial findings from oligo-pull down experiments suggest the proteins binding across the key associated and probably causal SNP, rs7903146, dimerize with TCF7L2. Dual luciferase reporter assays were performed in quadruplicate to determine the transcriptional activity under the control of the genomic region across rs7903146. Firefly luciferase constructs harboring each genomic element were co-transfected with an internal control vector, plus TCF7L2 or/ and beta-catenin, into 293T cells. Beta-catenin was analyzed as it is a well established key mediator of Wnt signaling via activation of TCF7L2. Our results revealed that TCF7L2 or beta-catenin separately were not sufficient to activate transcription. However, the combination of TCF7L2 and beta-catenin produced a striking increase of approximately 5 fold in transcription levels. These results suggest that the Wnt signaling pathway plays a crucial role in the regulation of TCF7L2 expression and that a possible alteration in this feedback mechanism via rs7903146 may at least in part explain the functional mechanism through which this variant confers T2D risk. Background: Despite identification and replication of multiple T2D susceptibility loci in genome-wide association studies (GWAS), much remains to be understood about the genetic background of T2D. Characterization of epigenetic variation across the genome can advance our understanding of genetic susceptibility to T2D. Methods: As in previous genetic studies among healthy individuals, we conducted an epigenome-wide association study (EWAS) on fasting insulin and glucose among 544 non-diabetic men and women in the Genetics of Lipid Lowering Drugs and Diet Network study. DNA was extracted from CD4+ T-cells isolated from frozen lymphocytes. CpG methylation at approximately 450,000 CpG sites was assayed using the Illumina Infinium HumanMethylation450 Beadchip. We used the LMEKIN package in R to implement a mixed model with methylation beta score (a measure of % methylation) as the dependent variable. In this model, insulin or glucose and covariates (age, sex, study site, and T-cell purity) were entered as fixed effects and family structure as a random effect. A Bonferoni corrected P-value of 1.1x10^-7 was considered significant. Results: In adjusted analyses, CpG06500161 was significantly associated with insulin (P=3.8x10^-8) and CpG01881899 approached genome-wide significance (P=6.2x10^-5) for insulin. Both CpG sites were identified on chromosome 21. Both CpG sites are found in the ATP-binding cassette sub-family G member 1 gene. Decreased function of ATP-binding cassette (ABC) transporters is associated with impaired insulin secretion and may explain the observed association. None of the CpG sites investigated was associated with fasting glucose after correction for multiple testing. Conclusions: Our findings suggest that differential methylation of CpG06500161within the ABCG1 locus may be associated with fasting insulin and merits further evaluation. Supported by: NIH (1U01HL072524) ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A431 POSTERS 1647-P Association of Plasma Glucose and Type 2 Diabetes Susceptibility Genes With Gestational Diabetes Epidemiology/ Genetics MARK O. GOODARZI, NAN WANG, CARL D. LANGEFELD, JINRUI CUI, ANNY H. XIANG, TALIN HARITUNIANS, YII-DER I. CHEN, KENT D. TAYLOR, JILL M. NORRIS, THOMAS A. BUCHANAN, DONALD W. BOWDEN, LESLIE J. RAFFEL, XIUQING GUO, RICHARD M. WATANABE, JEROME I. ROTTER, LYNNE E. WAGENKNECHT, Los Angeles, CA, Winston-Salem, NC, Pasadena, CA, Aurora, CO GENETICS—TYPE 2 DIABETES 1651-P 1653-P Genetic Variation Associated With Metformin Treatment Response Genotype-Associated TCF7L2 Splice Variants and Lipid Metabolism Provide Fine-Tuning of Wnt Pathway Regulation in Pancreatic BetaCells POSTERS Epidemiology/ Genetics NIENKE VAN LEEUWEN, GIEL NIJPELS, JACQUELINE M. DEKKER, ESTHER VAN ‘T RIET, KAIXIN ZHOU, EWAN R. PEARSON, LEEN M. ‘T HART, Leiden, Netherlands, Amsterdam, Netherlands, Dundee, United Kingdom PETER A. ANTINOZZI, WAYNE D. GRAHAM, ELLEN N. DOVER, Winston-Salem, NC Metformin is the first line treatment for type 2 diabetes. Unfortunately the glycaemic response to metformin is highly variable between individuals and genetic factors appeared to be involved in this variability. A genomewide association study (GWAS) by Zhou et al identified a locus near the ATM gene associated with metformin treatment response in T2D patients. In addition to the ATM locus other loci reached borderline significance (p<10 -5) and await confirmation in other studies. In the current study we aimed to replicate the effect of these genetic loci on metformin treatment response in T2D patients. Eleven SNPs with a minor allele frequency >5% in the by GWAS identified loci were measured in 620 patients on metformin monotherapy from the Diabetes Care System (n=7500), a large longitudinal cohort of Dutch type 2 diabetic subjects, using a Sequenom assay. We assessed if the ability to reach the treatment target of HbA1c ≤7% within one year after initiation of therapy was associated with genetic variation using logistic regression with baseline HbA1c, GFR and metformin dose as covariates. In addition to the previously reported replication of the ATM gene association we found that rs10007566 a SNP located between the SEPSECS and LGI2 genes on chromosome 4 is associated with treatment failure (OR=0.69 95% CI 0.530.89, p=0.005). This is in line with the original finding in the GWAS study and a meta-analysis combining our results with the published GWAS results in an OR=0.71 (95% CI 0.61-0.82, p=5.2*10 -7). Interestingly, SEPSECS is required for selenoprotein biosynthesis, a protein that is associated with T2D. There was no significant effect on treatment response observed with the other measured SNPs in our study, however five SNPs showed a trend in the same direction as in the original finding. In conclusion, using this large cohort of Dutch patients with type 2 diabetes, we have replicated that genetic variation near the SEPSECS/LGI2 genes is associated with metformin treatment failure. Wnt signaling is a tightly coordinated pathway which transcriptionally regulates cellular programs of proliferation and differentiation. TCF7L2 is a transcription factor in the Wnt pathway and is one of the leading T2Dassociated candidate genes. Previous studies have demonstrated the impact of genotype on the abundance of specific TCF7L2 splice variants, and here we evaluate the potency of these variants on a TCF reporter assay in β-cells. Expression of seven TCF7L2 variants comprising various exon combinations were evaluated in the INS1E β-cell line and differentially increased luciferase-based TCF reporter activity across a broad range (from 1.2 to 16 fold increases over basal levels). The presence of exon 4 in the splice variant decreases activity 80% as compared to matched variants lacking the exon. The presence of exon 4 containing variants was confirmed in human islets by RNA-Seq. Interestingly, when evaluated against a different reporter construct derived from the AXIN2 gene, a highly divergent ranking of potencies was observed for the seven variants compared to the initial reporter construct. This observation suggests that a given splice variant has differential effects across multiple TCF-responsive genes and each TCF7L2 variant may induce an altered gene expression profile. In INS1E cells, we observe that TCF reporter activity is dependent on the presence of Wnt ligand. Recent structural biology findings have shown an essential role of lipids mediating Wnt ligand interactions with its receptors. To evaluate if lipid signaling can attenuate Wnt activity in β-cells, we pharmacologically perturbed lipid metabolism and observed a dosedependent decrease in TCF reporter activity. Altogether, we demonstrate Wnt ligand stimulates transcriptional activity in β-cells and both lipids and the abundance of specific TCF7L2 isoforms can modulate this activity. Supported by: NIH/NIDDK (DK080151) 1654-P Supported by: Dutch Diabetes Research Foundation; ZonMw A Genome-Wide Association Study of Glycemic Response to Oral Glucose Tolerance Test in Gestational Diabetes Mellitus Women 1652-P SOO HEON KWAK, SUNG-HOON KIM, SUNG HEE CHOI, BO KYUNG KOO, HYE SEUNG JUNG, YOUNG MIN CHO, EUN ROH, YOON JI KIM, EUN KY KIM, TAE JUNG OH, MIN KYEONG KIM, SU MIN HONG, KYONG SOO PARK, HAK CHUL JANG, Seoul, Republic of Korea, Seoungnam-Si, Republic of Korea, Gyeonggi-Do, Republic of Korea Improved Performance of Precise Measures of Glucose Homeostasis over Surrogate Indices to Identify the Genetic Basis of Type 2 Diabetes: The GUARDIAN Consortium NICHOLETTE D. PALMER, LYNNE E. WAGENKNECHT, CARL D. LANGEFELD, THOMAS A. BUCHANAN, ANNY H. XIANG, HOOMAN ALLAYEE, RICHARD BERGMAN, LESLIE J. RAFFEL, YII-DER I. CHEN, MARK O. GOODARZI, TASHA FINGERLIN, KENT D. TAYLOR, TALIN HARITUNIANS, RICHARD M. WATANABE, DONALD W. BOWDEN, Winston-Salem, NC, La Canada, CA, Pasadena, CA, Los Angeles, CA, Aurora, CO Women with gestational diabetes mellitus (GDM) is thought to have reduced beta-cell insulin secretion that is insufficient to compensate for the increased insulin resistance during pregnancy. As these women do not use any anti-diabetic medication at the time of oral glucose tolerance test (OGTT), it is a unique opportunity to investigate the association between genetic variants and the severity of altered glucose homeostasis. We performed a two-stage genome-wide association analysis in 1,382 Korean GDM women. Study subjects underwent 100-g OGTT for diagnosis of GDM and both glucose and insulin levels were determined at 0-, 1-, and 2-hour of OGTT. Genotyping was performed using Affymetrix Genome-Wide Human SNP array 5.0 in stage 1 subjects (N=468) and by TaqMan method in stage 2 subjects (N=914). Variables that were investigated include fasting glucose, fasting insulin, index of beta-cell function (HOMA-B), index of insulin resistance (HOMA-IR), area under the curve (AUC) of glucose, and AUC of insulin. A variant in CA10, rs736146, was significantly associated with fasting glucose in stage 1 analysis (beta=-0.31 P=1.82E-06). However, this association was not significant in stage 2 subjects (beta=-0.01 P=0.13). The overall effect of this variant in fasting glucose was beta=-0.04 P=4.22E-05. A variant in ARL8B, rs13093380, was significantly associated with fasting insulin in stage 1 subjects (beta=0.34 P=5.10E-6). This variant was also significant in stage 2 analysis (beta=0.11 P=0.035) with overall effect of beta=0.19 P=9.96E-06. In addition, this variant was associated with HOMAIR (overall beta=0.19 P=9.33E-06). A variant in HHEX, rs7911264, was significantly associated with increased AUC of glucose (overall beta=0.17 P=6.84E-05) and decreased AUC of insulin (overall beta=-0.19 P=1.24E-05). These findings require further replication studies and functional investigation regarding the role of these variants are warranted. Type 2 Diabetes (T2D) is characterized by insulin resistance and compounded by beta-cell dysfunction. To date, genetic analyses have focused on T2D status and surrogate measures of insulin resistance and beta-cell function derived from plasma glucose and insulin. Alternatively, we investigated the genetic basis of dynamic measures of insulin secretion in Hispanic Americans from the GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium. Beta-cell function was measured as acute insulin response (AIR) to glucose challenge from the frequently sampled intravenous glucose tolerance test in 2,548 subjects. Complimentary measures included fasting glucose and insulin and HOMA2B which characterize betacell function at basal steady state. GWAS data from four independent cohorts (709,358 variants) was tested for association using meta-analysis approaches. We examined 60 previously documented T2D loci and compared associations between dynamic and fasting measures. Two genome-wide significant signals were identified for AIR in the MTNR1B gene (rs10830963, P=9.5E-12; rs1387153, P=1.4E-9; variance explained=2.06%). In contrast, nominal signals were observed for surrogate indices of glucose (rs10830963, P=1.5E-6), insulin (rs4869272, P=0.0032) or HOMA2B (rs560887, P=1.3E-4). Variants in CDKAL1 (rs9368222, P=4.7E-6), KCNQ1 (rs163184, P=2.7E-4) and TCF7L2 (rs7903146, P=5.1E-4) were nominally associated with AIR but showed no evidence of association with surrogate indices (P>0.010). These results suggest a specific role for these genes in first phase insulin release. This work highlights the improved power of precise measures of glucose homeostasis to identify T2D susceptibility loci in significantly smaller sample sizes. In addition, it suggests more comprehensive metabolic testing and associated genetic analysis can provide insight into the metabolic pathways influenced by specific genes. Supported by: Korea Healthcare Technology R&D Project (A111362) Supported by: NIH (DK085175), (DK081350), (DK097524) & For author disclosure information, see page 829. A432 Guided Audio Tour poster ADA-Funded Research GENETICS—TYPE 2 DIABETES 1655-P 1657-P Usefulness of Genetic Risk Score Constructed from 47 Loci for Type 2 Diabetes in Non-Obese, Older Japanese Individuals Type 2 Diabetes Genetic Associations in the Ashkenazi Jewish Population MINAKO IMAMURA, MINORU IWATA, HIROSHI MAEGAWA, HIROTAKA WATADA, HIROSHI HIROSE, YASUSHI TANAKA, KAZUYUKI TOBE, KOHEI KAKU, ATSUNORI KASHIWAGI, RYUZO KAWAMORI, SHIRO MAEDA, Yokohama, Japan, Toyama, Japan, Otsu, Japan, Tokyo, Japan, Kawasaki, Japan, Okayama, Japan TONI I. POLLIN, DANNY BEN AVRAHAM, NIR BARZILAI, BENJAMIN GLASER, GIL ATZMON, THE T2D-GENES CONSORTIUM, Baltimore, MD, Bronx, NY, Jerusalem, Israel Multiple genome-wide association studies have identified more than 50 loci associated with Type 2 Diabetes Mellitus (T2DM). We genotyped 2375 Ashkenazi Jewish subjects (1182 T2DM and 1193 non-diabetic) using the Metabochip SNP array. 70 cases and 58 controls were excluded due to cryptic relatedness, ethnic outliers, sex assignment errors or poor quality DNA. SNPs which were monomorphic, had call rates <0.90 or were not in Hardy-Weinberg Equilibrium (p<10-7) were excluded, leaving 144,775 SNPS for this analysis. Logistic regression analysis with an additive model adjusted for age and sex yielded 50 SNPs in 19 distinct chromosomal regions associated with T2DM at p <0.0001 with odds ratios ranging from 1.31 to 2.30, including several variants in the TCF7L2 region with p <10-7, the most significantly being rs7903146 in TCF7L2 (OR = 1.50, p = 3 x 10-8). Of 99 T2DMassociated SNPs identified in the recent T2DM Metabochip meta-analysis and successfully genotyped in the Ashkenazi Jewish sample, 24 (24%) were nominally (p <0.05) associated with type 2 diabetes, all directionally consistent with previous reports, with ORs ranging from 1.15 to 1.50. In conclusion, some but not all SNPs previously associated with T2DM were nominally replicated in The Ashkenazi population, including TCF7L2 SNP rs7903146 at genome-wide significance. To investigate a clinical usefulness of currently available genetic information, we examined a combined effect of type 2 diabetes (T2D) susceptible loci by constructing genetic risk score (GRS) in a Japanese population. First, we examined up to 11,532 Japanese individuals for 55 T2D susceptible single nucleotide polymorphisms (SNPs), and selected 47 SNPs which showed consistent effect direction with the original reports [Odds Ratio (OR)>1]. GRS was constructed in 2,648 T2D cases and 1,802 controls, whose genotype information for the 47 SNPs was complete, by counting the number of risk alleles of the 47 SNPs in each individual. The GRS was significantly associated with T2D [p =7.22 × 10 -44, OR per risk allele = 1.12, 95%Confidence Interval (CI) = 1.10- 1.13]. In Receiver Operating Characteristic (ROC) analysis, the area under the curve (AUC) for GRS alone (model 1) was 0.623, whereas the AUC for age, sex and BMI (model 2) was 0.743. The addition of the GRS to model 2 (model 3) resulted in a small, but significant increase in the AUC (AUC for model 3 = 0.774, p-value for model 2 vs model 3 = 1.85×10 -15, ΔAUC (model 3- model 2) = 0.031). In an age or BMI stratified analysis, effect of the GRS was stronger in older (age ə 50, AUC for model 1 = 0.635, model 2 = 0.623, model 3 = 0.684. p-value for model 2 vs 3 = 1.58×10 -11, ΔAUC = 0.061), or in non-obese individuals (BMI < 25 , AUC for model 1 = 0.640, model 2 = 0.769, model 3 = 0.800. p-value for model 2 vs 3 = 5.06×10 -12, ΔAUC = 0.031). The GRS was also significantly associated with age of diagnosis (AOD) in 1,073 T2D (β = - 0.17, S.E. = 0.085, p = 0.046) or with fasting plasma glucose in 812 controls (β = 0.168, s.e. = 0.073, p = 0.021). In conclusion, the GRS was significantly associated with T2D risk and T2D-related traits in the Japanese. Although currently available genetic information is still not sufficient for the prediction of T2D onset, the information may be more useful in non-obese, older individuals. Supported by: Grant-in-Aid for Scientific Research (C23591361); MEXT (Japan) The SIGMA Diabetes Consortium recently reported a GMA in Hispanics (American Society for Human Genetics, 2012), which identified a novel missense variant (rs13342232) associated with T2D in SLC16A11, an uncharacterized member of a family of mono-caboxylic acid transporters. SLC16A1-4 are involved in proton-linked transport of lactate and pyruvate giving SLC16A11 strong biologic relevance. The Genetics Underlying Diabetes in Hispanics (GUARDIAN) Consortium, comprised of 7 cohorts, aims to identify genetic loci underlying T2D-related QTs in 4139 nondiabetic subjects from 1875 Hispanic families. QTs of primary interest are insulin sensitivity and metabolic clearance rate of insulin (MCRI), but also include fasting glucose and fasting insulin. Insulin sensitivity was measured by FSIGT with minimal model or by euglycemic clamp. Genotyping was performed using Illumina OmniExpress and a GMA was conducted combining individual cohort association results using METAL. We examined 150 SNPs within SLC16A11 (~2.3kb) and the 250 kb flanking regions. None of the SNPs within SLC16A11 were associated with any T2D-related QT. We found 2 proxy SNPs (r2 = 1.0) for rs13342232, but the strongest association was with fasting glucose (P = 0.19). rs2047774, 82 kb upstream of SLC16A11 and near ASGR2, showed evidence for association with insulin sensitivity (P = 7.0×10 -4); while rs8078000, 337 bp upstream of SLC16A11, showed more modest evidence for association with insulin sensitivity (P = 1.3×10 -3). These 2 SNPs were not in LD (r2 = 0.01) nor in LD with the tag SNPs for rs13342232 (r2 < 0.05). Our results suggest SLC16A11 is not associated with insulin sensitivity, MCRI, fasting glucose or fasting insulin in Hispanic Americans. In contrast, we observed an association with insulin sensitivity near ASGR2, a hepatic asialoglycoprotein receptor mediating endocytosis and lysosomal degradation of glycoproteins. 1656-P A Genome-Wide Association Study of Glycemic Response to Rosiglitazone SOO HEON KWAK, EUN ROH, EUN SEOK KANG, CHENG HU, MIN KYONG MOON, EUN YOUNG CHOE, RONG ZHANG, YOUNG MIN CHO, HYE SEUNG JUNG, EUN K.Y. KIM, YOON JI KIM, TAE JUNG OH, MIN KYEONG KIM, SU MIN HONG, WEIPING JIA, HYUN CHUL LEE, KYONG SOO PARK, Seoul, Republic of Korea, Shanghai, China Rosiglitazone is a thiazolidinedione anti-diabetic drug that acts as an insulin sensitizer. It binds to peroxisome proliferator-activated receptor gamma and activates expression of its target genes. There are individual variations in response to this medication and genetic predisposition could be one of the factors that contribute to this variation. We performed a twostage genome-wide association analysis in 434 East Asians type 2 diabetes patients. Study subjects received rosiglitazone 4mg/day for 4-6 months and glycemic response was evaluated before and after the treatment using fasting glucose and HbA1c. Responders were defined as those with 20% decrease in fasting glucose or 15% decrease in HbA1c after 4-6 months of rosiglitazone treatment. We performed a case-control genetic association analysis as well as quantitative trait analysis for the change in fasting glucose or HbA1c level. Among the 195 stage 1 subjects (SNUH), 139 (71.3%) were classified as responders and 56 (28.7%) as non-responders. Stage 1 subjects were genotyped using Affymetrix Genome-Wide Human SNP array 5.0. We selected 8 genetic variants for follow-up genotyping in 146 independent Korean subjects (YUMC) and 93 Chinese subjects (SJTU). A intronic variant (rs11676659) in STAT4 (signaling transducer and activator of transcription 4) had strong association with overall non-response to rosiglitazone in stage 1 subjects (OR=4.35, P=9.83E-06). Although the direction of its association was the same, it did not have significant association in stage 2 samples (YUMC OR=1.32 P=0.44, SJTU OR=1.95 P=0.29). The effect of this variant estimated by meta-analysis of three studies was OR=2.43 P=9.83E-05. This variant was also associated with attenuated fasting glucose lowering effect in the meta-analysis of three studies (beta=0.74 P=7.58E-05). This finding requires further replication studies and functional investigation regarding the role of STAT4 in rosiglitazone response is warranted. 1659-P DPP4 Gene Variation Affects GLP-1 Secretion, Insulin Secretion, and Glucose Tolerance in Humans With High Body Adiposity HARALD STAIGER, KATRIN STAIGER, ANJA BÖHM, MARTIN HENI, KATARZYNA LINDER, FAUSTO MACHICAO, NORBERT STEFAN, ANDREAS FRITSCHE, HANSULRICH HÄRING, Tübingen, Germany Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), collectively termed incretins. DPP-4 inhibitors entered clinical practise as approved therapeutics for type 2 diabetes in 2006. However, interindividual variance in the responsiveness to DPP-4 inhibitors was Supported by: Korea National Project for Personalized Genomic Medicine (A111218-GM09) ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A433 POSTERS NAN WANG, MARK O. GOODARZI, CARL D. LANGEFELD, XIUQING GUO, TALIN HARITUNIANS, JEROME I. ROTTER, TASHA E. FINGERLIN, LESLIE J. RAFFEL, IDA CHEN, LYNNE E. WAGENKNECHT, RICHARD M. WATANABE, Los Angeles, CA, Winston-Salem, NC, Aurora, CO Epidemiology/ Genetics 1658-P A Genome-Wide Meta-Analysis (GMA) Shows No Evidence of Association Between Newly Identified Type 2 Diabetes (T2D) Locus SLC16A11 and T2D-Related Quantitative Traits (QTs) in Hispanic Americans GENETICS—TYPE 2 DIABETES T2D, including dietary pattern, physical activity, alcohol intake, usual sleep duration, smoking status, and body mass index. A multivariable logistic regression model was used to estimate odds of diabetes risk for each level of the genetic and lifestyle scores, and the interaction between them. Both scores were associated with diabetes odds (p<.0001 for both). The test of multiplicative interaction between the genetic and lifestyle scores did not reach significance (p=.08). The table shows the proportion of T2D cases and the odds ratios for T2D according to the levels of the genetic and lifestyle risk. Our data suggest that lifestyle modification is highly efficacious for preventing T2D, independent of genetic risk. reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type 2 diabetes (TÜF). Fourteen common (minor allele frequency ≥0.05) DPP4 tagging single nucleotide polymorphisms (SNPs) were genotyped in 1,976 non-diabetic TÜF participants characterized by oral glucose tolerance tests and bioimpedance measurements. In a subgroup of 168 subjects, plasma incretin levels were determined. We identified a variant, i.e., SNP rs6741949, in intron 2 of the DPP4 gene that, after correction for multiple comparisons and appropriate adjustment, revealed a significant genotype-body fat interaction effect on glucosestimulated plasma GLP-1 levels (p=0.0021). Notably, no genotype-BMI interaction effects were detected (p=0.8). After stratification for body fat content, the SNP negatively affected glucose-stimulated GLP-1 levels (p=0.0229), insulin secretion (p=0.0061), and glucose tolerance (p=0.0208) in subjects with high body fat content only. In conclusion, a common variant, i.e., SNP rs6741949, in the DPP4 gene interacts with body adiposity and negatively affects glucose-stimulated GLP-1 levels, insulin secretion, and glucose tolerance. Even though its mechanism remains to be shown, the SNP could possibly underlie the reported interindividual variance in responsiveness to DPP-4 inhibitors, especially in subjects with high body fat content. 1660-P Variation in PPARG Is Associated With Longitudinal Change in Insulin Resistance, Independent of Adiposity, in Mexican Americans Supported by: NIH (R01DK080720), (R01CA55069), (R35CA53890), (R01CA80205), (R01CA144034) POSTERS Epidemiology/ Genetics MARY HELEN BLACK, JUN WU, MIWA TAKAYANAGI, KENT D. TAYLOR, TALIN HARITUNIANS, ENRIQUE TRIGO, JEAN M. LAWRENCE, RICHARD M. WATANABE, THOMAS A. BUCHANAN, ANNY H. XIANG, Pasadena, CA, Los Angeles, CA 1662-P Peroxisome Proliferator-Activated Receptor-gamma (PPARG) is a known susceptibility locus for type 2 diabetes (T2D). Although cross-sectional associations have been reported for Pro12Ala and other variants in the region, longitudinal studies are lacking. We examined the effects of variation in PPARG on longitudinal changes in anthropometric and metabolic traits in a subset of 378 BetaGene participants (mean age: 39.8 ± 8.3 years; 74.5% female) with follow-up phenotyping (median length of follow-up: 4.2 years, IQR: 3.4-5.6). Phenotypes include body fat assessed by DXA, and insulin sensitivity (SI), acute insulin response and β-cell function (disposition index; DI) estimated from FSIGTs with Minimal Model analysis. Sixteen tag SNPs capturing variation in a 135 kb region surrounding PPARG were tested for association with rates of change in anthropometric and metabolic traits, adjusting for age and sex. An additive genetic model was assumed for SNPs with MAF > 15%, and a dominant model was used otherwise. All p-values reported are Bonferroni-corrected for the number of tag SNPs tested. Three SNPs, rs2920500, rs17793951 and rs1151996, were significantly associated with the rate of change in SI (p=0.032, p=0.012 and p=0.005, respectively), but not with changes in adiposity (all p>0.99). rs17793951 also had a significant effect on change in DI over time (p=0.037). Further adjustment for baseline and/or changes in adiposity over time did not alter these results. rs2120825 was associated with the rate of change in BMI (p=0.041), and showed trend for association with changes in body fat percentage (p=0.12) and SI (p=0.14). rs1306470 (captures Pro12Ala, pairwise r2=0.9) was not significantly associated with the rate of change in any anthropometric or metabolic traits (all p>0.17). These data provide evidence that variation in PPARG contributes to declining SI and deteriorating β-cell function, independent of adiposity, in Mexican Americans at risk for T2D. Genetic Basis of Diabetes Resistance and Sensitivity in Obese Mice OLIVER KLUTH, HEIKE VOGEL, DANIELA MATZKE, STEPHAN SCHERNECK, DANIEL KAISER, HANS-GEORG JOOST, ANNETTE SCHÜRMANN, Nuthetal, Germany New Zealand Obese (NZO) mice are diabetes prone but can be protected from β-cell loss by carbohydrate restriction, whereas obese mice on C57BL/6background (B6-ob/ob) never develop diabetes. Our aim was to elucidate the pathogenesis of β-cell loss in the NZO strain and to clarify how B6-ob/ob mice are protected from T2D. NZO and B6-ob/ob mice were fed a fat-enriched, carbohydrate-free diet up to week 18 to generate obesity but without β-cell failure. Subsequently, the mice received a diabetogenic carbohydratecontaining diet for up to 32 days. Alterations in p-AKT and PDX1 levels were investigated in islets. Transcriptome analysis was performed with islet RNA from both strains fed with or without carbohydrates for 2 days. Differentially expressed genes mapping to quantitative trait loci in a F2 generation of NZO and C57BL/6 were identified. Glucolipotoxicity caused loss of NZO islets due to impaired AKT-signaling, decreased PDX1 and apoptosis. In contrast, islets from B6-ob/ob mice maintained normal levels of p-AKT and PDX1 in their islets. Transcriptome analysis of islet-RNA indicated that only B6-ob/ob mice respond to carbohydrates with an upregulation of genes involved in β-cell proliferation. Moreover, 7 genes that were almost exclusively expressed in NZO islets were identified within loci for obesity and hyperglycaemia on chromosomes 1, 11, 15, and 19. Amongst them is Ifi202b which we recently discovered as novel adiposity gene. Due to a microdeletion of Ifi202b, it is not expressed in B6-ob/ ob islets. Data obtained by characterizing recombinant congenic mice indicate that the presence of Ifi202b suppresses the induction of compensatory β-cell proliferation under glucolipotoxic conditions. Impaired AKT-signaling and lack of glucose-dependent induction of β-cell proliferation are responsible for β-cell loss in diabetes-susceptible mice. The loss of function of Ifi202b that appears to inhibit cell division protects diabetes-resistant mice from hyperglycaemia. 1661-P Interactions of Type 2 Diabetes Susceptibility Loci and Lifestyle in Singaporean Chinese MARK A. PEREIRA, CHRIS HSU, DANIEL STRAM, ANDREW O. ODEGAARD, MARK SEIELSTAD, M. WOON-PUAY KOH, YIK YING TEO, E. SHYONG TAI, JIANJUN LIU, JIAN-MIN YUAN, MYRON D. GROSS, Minneapolis, MN, Los Angeles, CA, San Francisco, CA, Singapore, Singapore, Pittsburgh, PA The Relationship between Serum BDNF and Cognitive Impairment Depends on the BDNF Val66Met Polymorphism in T2DM Patients Little is known about gene-environment interactions for type 2 diabetes(T2D). We studied whether the association between previously identified T2D single-nucleotide polymorphisms (SNPs), and SNPs in nearby regions, with risk of incident T2D would be modified by lifestyle in Singaporean Chinese. Using an Affymetrix GW ASI SNP array augmented by imputation based on the 1,000 genomes project we successfully genotyped or imputed (with R2≥ 0.8) over 7.5 million SNPs in 4678 participants (2338 cases with T2D and 2340 controls). We selected 98 genotyped or imputed T2D-related SNPs (p<10-5) from the NHGRI GWAS Catalog for replication. A 9-point lifestyle index was created from 6 independent predictors of Studies suggest that brain-derived neurotrophic factor (BDNF) plays an important role in modulating synaptic transmission and activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Type 2 diabetes (T2DM) is associated with cognitive impairment in many domains, and has an increased risk of vascular dementia and Alzheimer disease, which may result from decreased BDNF and its Val66Met polymorphism. However, the correlations of cognitive impairment with serum BDNF and its Val66Met polymorphism have not been investigated in T2DM. 1663-P YAN FENG ZHEN, HUI FANG, XING YU LIU, XIANG YANG ZHANG, DONG HAO ZHOU, SHAO XIONG ZHENG, Tangshan, China, Houston, TX, Tianjin, China & For author disclosure information, see page 829. A434 Guided Audio Tour poster ADA-Funded Research GENETICS—TYPE 2 DIABETES We compared 311 patients with T2DM to 346 normal controls on serum BDNF levels and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). BDNF Val66Met polymorphism was examined using the PCR-RFLP method in all subjects. We found that serum BDNF levels in T2DM patients were significantly lower than that of normal controls (p<0.001). The total score and nearly all indexes (all p<0.01) except for attention and visuospatial/constructional indexes (all p>0.05) of RBANS were markedly decreased in T2DM compared to normal controls. Serum BDNF was positively associated with delayed memory index score in patients with T2DM (p<0.05). The delayed memory index score was significantly lower in Val/Val carriers than the Met/Met carriers (p<0.05). Furthermore, among Met homozygote patients, BDNF levels were positively associated with the delayed memory index score (β=0.29, t=2.21, p=0.033), but inversely associated with the RBANS total score (β=-0.92, t=-3.40, p=0.002) among Val homozygote patients. Our results indicate that BDNF may be involved in the pathophysiology of cognitive impairment, especially delayed memory in T2DM. The relationship between serum BDNF and cognitive impairment depends on the presence of BDNF Val66Met polymorphism in T2DM patients. Nominally statistically significant associations were seen with SNPs in FTO (rs1421085, b=1.9% increase in BMI per risk allele, r=0.05, P=0.020) and TMEM18 (rs2867125, b=2.8% r=0.06, P=0.0007); these associations are consistent with those reported in other populations. The multiallelic score was also associated with BMI (b=0.5%, r=0.06, P=0.002), and it remained nominally significant, though attenuated, when the FTO and TMEM18 SNPs were excluded from consideration (b=0.3%, r=0.04, P=0.048). This study suggests that common genetic variants established as associated with obesity in Europeans also influence variation in BMI in Pima Indians. The strongest associations are with variants in FTO and TMEM18, but these results suggest that many other variants, though not individually significant, may play a modest role in obesity in this population. 1664-P Type 2 diabetes (T2D) is a chronic, heterogeneous disease and a major risk factor for cardiovascular diseases. The underlying mechanisms leading to progression to T2D are not fully elucidated. We hypothesized that genetic risk factors play a role in glycemic deterioration and that validated genetic variants are associated with T2D progression in American Indians. Using prospective data of the Strong Heart Family Study (2 to 3 visits, up to 10 years of follow up), we identified 434 individuals defined as progressors (T2D incident cases or persistent impaired fasting glucose [IFG]), 1,011 controls (normal fasting glycemia [NFG] at all visits) and 566 individuals with transitory IFG (prospectively transition from NFG to IFG or IFG to NFG). We estimated heritability (h2) of the traits, segregation in pedigrees and evidence for association with 17 validated variants from T2D genome wide association studies. We noted high heritability for T2D progression (h2=0.63) but little contribution of genetic factors to transitory IFG (h2=0.09). At least three variants (in WFS1, TSPAN8 and MTNR1B) were significantly associated with T2D progression in adjusted analyses accounting for multiple testing. Our findings provide evidence for generalization of validated T2D variants to T2D progression in American Indians, a population with high rates of obesity and T2D, and suggest phenotypic heterogeneity of the IFG trait which may have implications for genetic studies when diagnosis is based on a single time-point measure. 1666-P Genetic Determinants of Progressive Deterioration of Glycemia in American Indians GABRIELA DA SILVA XAVIER, ANGELES MONDRAGON, RYAN MITCHELL, DAVID HODSON, JORGE FERRER, BERNARD THORENS, JAMES MCGINTY, PAUL FRENCH, GUY A. RUTTER, London, United Kingdom, Barcelona, Spain, Lausanne, Switzerland Single nucleotide polymorphisms in the transcription factor T-cell factor 7 like-2 (TCF7L2) gene, including rs7903146, are associated with an elevated risk of type 2 diabetes in man. TCF7L2 encodes a member of the TCF family of transcription factors involved in the control of cell growth and signalling downstream of wingless-type MMTV integration site family (Wnt) receptors. Mice inactivated for Tcf7l2 throughout the pancreas using Pdx1.Cre-mediated recombination display impaired glucose tolerance, beta cell expansion and insulin secretion, particularly in response to GLP-1. To achieve deletion more specifically in the adult pancreatic beta cell we have used here mice in which Cre recombinase was knocked-in at the Ins1 locus. Compared to littermate controls Ins1.Cre::Tcf7L2fl/fl mice bred on a C57BL/6 background displayed impaired intraperitoneal glucose tolerance by 16 weeks (increase in AUC of 13.6 ± 2.8 %, n=6 mice per genotype), and impaired oral glucose tolerance from 8 weeks (increase in AUC of 10.6 ± 1.3 %, n=6), values similar to those previously observed in Pdx1.Cre::Tcf7l2fl/fl mice (where glucose intolerance was observed at 20 and 12 weeks when glucose was administered by the intraperitoneal or oral route, respectively). These findings provide further evidence for a cell-autonomous role for Tcf7L2 in the beta cell and suggest that lowered levels of active TCF7L2 in these cells may contribute to the effects of the risk allele. The impact of Tcf7l2 deletion on isolated islet function, pancreatic beta cell mass, and the effect of maintenance on a high (60 %) fat diet are currently under investigation. Supported by: NIH 1667-P A Common Variant Near ATM Is Associated With Metformin Treatment Response in Type 2 Diabetes SIMIN ZHANG, DEHONG CAI, YAN LI, XIAOHUI GUO, QING SU, LIXIN GUO, QUANMIN LI, DONG ZHAO, HONGMEI LI, JIANGMING LANG, BO FENG, JING LIN, YAJUN LI, XUEYAO HAN, LINONG JI, Beijing, China, Guangzhou, China, Shanghai, China, Foshan, China Supported by: EFSD; Wellcome Trust; MRC Objective: A recent genome-wide association study in Caucasian has identified a novel genetic loci near ATM for metformin treatment response of type 2 diabetes (T2D). Our purpose was to determine whether the SNP can be replicated in Chinese Han population. Methods: In this study, 145 newly diagnosed Chinese Han subjects with type 2 diabetes (HBA1C<10%) without treatment were included. All the patients were administered with metformin monotherapy for 16 weeks. Measure the HbA1c level on baseline and 16 weeks. The patients were divided into efficient group and inefficient group according to the reduction of HbA1c level after metformin treatment. The SNP rs11212617 was genotyped by Goldengate chip in 145 T2D patients. The association of rs11212617 with metformin response in T2D was analyzed by logistic regression after adjustment by BMI, sex and age at baseline. Results: After 16 weeks treatment, the mean of HbA1c level decreased from 8.33±0.8% to 6.53±0.6%, the median of reduction was 1.8%. The HbA1c reduction of 71 subjects were more than 1.8% (efficient group) and 74 subjects of 145 patients were less than 1.8% (inefficient group). This case-control study showed that there was significent difference in allele frequence between these two groups. The patients with minor allele A have better glycemia response to metformin than the patients without allele A. with a Odd Ratio (OR, 95%CI) 2.5(1.47-4.24) and p value = 0.0007 after adjust for BMI, age, sex. Conclusions: In our study, the variant rs11212617 near ATM gene was observed to be associated with glycemia control ability of metformin in 1665-P Analysis of Established Obesity Variants in American Indians ROBERT L. HANSON, SAYUKO KOBES, WILLIAM C. KNOWLER, CLIFTON BOGARDUS, LESLIE J. BAIER, Phoenix, AZ Several single nucleotide polymorphisms (SNPs) are reproducibly associated with body mass index (BMI) in European and European-derived populations. There is little information, however, on their relationships with BMI in American Indian populations, many of which have a high prevalence of obesity. We genotyped a “sentinel” SNP at 27 of the established obesity loci in 3227 Pima Indians (1868 women, 1359 men, mean age=36.3 years) who had participated in a longitudinal study; the maximum BMI observed over the course of the study was taken as a measure of obesity (mean BMI=37.5 kg/m2). Eight SNPs (at MC4R, PCSK1, LRP1B, CADM2, SLC39A8, QCPTL and FANCL) had minor allele frequency<0.01; the remaining 19 SNPs were analyzed for association with BMI. A linear mixed model, accounting for familial relationships, was used to calculate the correlation of BMI with the number of risk alleles, as determined by previous studies, and the effect of each risk allele (b), expressed as a multiplier, on BMI. A multiallelic risk score, constructed by summing the number of risk alleles over all loci, was also analyzed. ADA-Funded Research & For author disclosure information, see page 829. Guided Audio Tour poster A435 POSTERS Defective Glucose Homeostasis in Mice Inactivated Selectively for Tcf7L2 in the Adult Beta Cell With an Ins1-Controlled Cre Epidemiology/ Genetics NORA FRANCESCHINI, KARIN HAACK, HARALD H.H. GORING, V. SAROJA VORUGANTI, SANDRA LASTON, LYLE G. BEST, RICHARD R. FABSITZ, JAMES B. MEIGS, JAMES B. PANKOW, SHELLEY A. COLE, Chapel Hill, NC, San Antonio, TX, Timber Lake, SD, Bethesda, MD, Boston, MA, Minneapolis, MN GENETICS—TYPE 2 DIABETES Chinese Han population with T2D. The results should be replicated further within large scale sample. 1670-P Identification and Functional Characterization of Hepatocyte Nuclear Factor-1B (MODY 5) Gene Mutations in Indian Diabetic Patients With Renal Abnormalities 1668-P SEKAR KANTHIMATHI, KANDASAMY BALAMURUGAN, COIMBATORE SUBRAMANIAM SHANTHI RANI, VISWANATHAN MOHAN, VENKATESAN RADHA, Chennai, India TCF7L2 Gene Polymorphisms May Influence the Risk of Type 2 Diabetes Mellitus by Effect on Insulin Sensitivity Independently from BMI and Body Fat Content Mutations in the HNF1B have been reported to be responsible for maturity-onset diabetes of the young (MODY5) associated with renal abnormalities. We aimed to identify and functionally characterize the HNF1B mutations in a cohort of 40 unrelated diabetic patients with various renal abnormalities seen at our centre. Direct sequencing of HNF1B revealed 3 known heterozygous mutations namely -67C>T, R165H, IVS2nt+2insT and 1 novel mutation N321D in these patients. The promoter mutation -67C>T was identified in a patient with focal and segmental glomerulosclerosis. The functional consequence of this mutation is unclear. The R165H mutation was identified in a patient with bilateral small kidneys and left renal cortical cyst. This mutation has been shown to disrupt protein folding/stability. The IVS2nt+2insT splice site mutation was found in the proband with dual collecting system in the right kidney and small sized left kidney with renal cyst and is known to result in a truncated protein lacking transactivation domain. A novel homozygous mutation N321D was identified in a patient with renal aplasia. The amino acid asparagine (N) residue at position 321 is evolutionarily conserved among human, rat and mouse species, therefore we further characterized this mutation to determine its function and molecular pathophysiology. We investigated the transcriptional activity of N321D mutation (both heterozygous and homozygous state) on human Glut2 and Rat albumin promoter in HeLa and Hek293 cells. The wild type and N321D mutant proteins exhibited equal level of transactivation potential in HeLa and Hek293 cell lines. Western blot analysis also showed similar level of wild type and N321D mutant protein expression, indicating the protein stability to be normal in the mutant. Subcellular localization assays also revealed normal transportation of protein to the nucleus. This is the first major study of HNF1B mutations (MODY5) from India. POSTERS Epidemiology/ Genetics ADAM KRETOWSKI, EDYTA ADAMSKA, NATALIA WAWRUSIEWICZ-KURYLONEK, ANNA CITKO, JOANNA GOSCIK, KATARZYNA MALISZEWSKA, JULIUSZ WILK, MAGDALENA WASZCZENIUK, DANUTA LIPINSKA, JUSTYNA PLISZKA, MICHAL CIBOROWSKI, MARIA GORSKA, Bialystok, Poland The genome-wide association studies have recently expanded the number of genetic susceptibility loci for type 2 diabetes and obesity. Transcription factor 7-like 2 (TCF7L2) gene seems to be one of the most predictive identifiable factors promoting T2DM development. It has been suggested that TCF7L2 influences pancreatic β-cell function but the effect of genetic variants of TCF7L2 on metabolic syndrome development is not well characterized among subjects with obesity. The aim of our study was to analyze whether genetic variants of the TCF7L2 gene influence fasting leptin levels and insulin sensitivity in nondiabetic obese/overweight subjects. We genotyped previously identified TCF7L2 SNPs: rs7901695 and rs7903146 in 944 subjects (463 women, 481 men), who underwent anthropometry (BMI) and body composition analysis: percent of body fat, visceral and subcutaneous abdominal adipose tissue by multi-frequency bio-impedance method. In the present study we found that subjects with TT rs7903146 TCF7L2 homozygotes presented significantly higher fasting levels of leptin (29.7 vs. 19.7 ng/ml, p=0,035) and higher homa-IR (3.9 vs. 2.6, p=0,009), despite the lack of differences in BMI, body fat content and body fat distribution. Moreover In the logistic regression analysis presence of CC genotype of rs7901695 TCF7L2 predicted higher IR independently from BMI, gender and caloric intake (p<0.01). We believe that our study may help to understand the pathways that TCF7L2 gene influence the risk of T2DM and provide personalized treatments and prevention strategies to fight against type 2 diabetes. Supported by: MNiSzW (4774/B/P01/2009/37) 1671-P Application of MODY Probability Calculator for Japanese Patients With MODY3 1669-P Genome-Wide Association Study Identifies Susceptibility Loci for Type 2 Diabetes and Impaired Glucose Regulation in Young Korean Women NAOKO IWASAKI, MIHO TAKIZAWA, RISA IDE, MAKIKO OGATA, YASUKO UCHIGATA, Tokyo, Japan Maturity-onset diabetes of the young type (MODY) is a subtype of diabetes caused by a single gene disorder typically with autosomal dominant inheritance and younger age of onset without obesity. A diagnosis of MODY is confirmed by a genetic testing, however, its cost and availability limit to perform the genetic testing. Recently, MODY probability calculator was developed to estimate the positive predictive value for genetic testing for patients suspected with MODY (http://www.diabetesgenes.org/). The aim of the study was to validate its efficacy in Japanese patients with MODY, since the calculator was developed on European Caucasian cohort. Twenty patients (16 families) were identified the mutations in HNF1A, including one subject who has not develop diabetes at current age of 36 years, and three patients who were diagnosed with diabetes at older than 30 years. After excluding those four individuals, we used 16 patients for the study. The mean age at diagnosis and BMI were 16.9 ± 6.6 years and 20.3 ± 2.1. Parental family history was observed in 15 families (94%). Nine patients were referred by school health checking for urinary glucose. For the calculation, 12 patients who had full information were used and four cases who do not have information for current treatment, we run all possible patterns and then calculate the mean provability. Among 12 subjects with full parameters, 11 subjects showed >75.5% positive predictive value. One patient who showed 1.9% was diagnosed at 9 years of age and started insulin immediately, in addition, GAD antibody had not tested at the onset year of 1975. She had a mother with diabetes. Mean probability score for the remaining 4 subjects were 56.8%, 21.3%, 50.5% and 58.6%, and mean positive predictive value with 16 patients was 63.7%. MODY probability calculator developed for Caucasian MODY can be applicable in Japanese patients with MODY. More than half of MODY3 subjects were initially detected by school health checkup. HYEJIN LEE, YEON-AH SUNG, JEE-YOUNG OH, Seoul, Republic of Korea The global epidemic of type 2 diabetes mellitus (T2DM) and prediabetes is one of the most challenging problems of recent days. Substantial evidence suggests that T2DM is a multifactorial disease with a strong genetic component. The aim of this study was to identify causative genes of T2DM and impaired glucose regulation (IGR: impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)) in young Korean women. We conducted genome-wide association study (GWAS) of T2DM and IGR in 2,000 young Korean women (17 T2DM, 123 IFG or IGT, and 1780 controls, mean age: 25±5 years (16~39 years)). DNA from individuals was genotyped using the Illumina HumanOmni1 Quad array. After quality-control procedures, we retained genotypes for 636,870 SNPs. PLINK was employed to conduct association tests for the allele data with logistic regression. We identified strong evidence of associations between T2DM/IGR and one loci (7p 15.3, rs730497; P value = 7.154 x 10 -9, OR = 2.153), and weak association between T2DM/IGR and multiple SNPs (rs 4607517, rs1004558, rs2348424, rs6875501, rs758982, rs10786907, rs16827528, rs10476783, rs6872336, rs10210850, rs6759214, rs4344883, rs3866790, rs12209009, rs4402698, P value = 9.62 x 10 -7 ~ 8.159 x 10 -6). At 7p15.3, rs730497 located within glucokinase (GCK) gene, which is associated with T2DM, maturity onset diabetes of the young, type 2 (MODY2). Although we could not find the previously identified T2DM associated genes, we found that GCK gene was associated with T2DM and IGR in young Korean women. We might consider that the pathogenesis for the development of hyperglycemia in young women may be different from typical T2DM. However further replication studies are needed to confirm these findings. Supported by: MEXT (Japan); Ministry of Health and Welfare (Japan) & For author disclosure information, see page 829. A436 Guided Audio Tour poster ADA-Funded Research GENETICS—TYPE 2 DIABETES 1672-P 1674-P Serum Resistin Is Positively Associated With Peripheral Neutrophil and Monocyte Counts Independent of Resistin SNP-420 and SNP358: The Toon Genome Study The IRS1 G972R Polymorphism and Glomerular Filtration Rate in Patients With Type 2 Diabetes Mellitus SALVATORE DE COSMO, SABRINA PRUDENTE, OLGA LAMACCHIA, LAURA PUCCI, DANIELA LUCCHESI, CHRISTINE MENDONCA, DIEGO BAILETTI, MASSIMILIANO COPETTI, FABIO PELLEGRINI, MAURO CIGNARELLI, GIUSEPPE PENNO, ALESSANDRO DORIA, VINCENZO TRISCHITTA, San Giovanni Rotondo, Italy, Foggia, Italy, Pisa, Italy, Boston, MA RYOICHI KAWAMURA, YASUHARU TABARA, WATARU NISHIDA, ISAO SAITO, YASUNORI TAKATA, MAYO AIBIKI, YUKINOBU NOMI, YUKO KADOTA, AI OKAMOTO, TATSUYA NISHIMIYA, HIROSHI ONUMA, TETSURO MIKI, TAKESHI TANIGAWA, HARUHIKO OSAWA, Toon, Ehime, Japan, Kyoto, Japan Resistin, secreted from adipocytes, induces insulin resistance in mice. We reported that single nucleotide polymorphism (SNP) -420 (rs1862513) in the human resistin gene was associated with type 2 diabetes susceptibility (Am J Hum Genet 75: 678, 2004). In the general Japanese population, circulating resistin was strongly associated with SNP-420 and SNP-358 (rs3219175) (PLoS ONE 5: e9718, 2010). In humans, resistin is predominantly expressed in macrophages. However, the association between either serum resistin or its SNPs and differential white blood cell (WBC) count in general populations remains to be elucidated. The Toon Genome Study is a cohort study for surveying risk factors for cardiovascular diseases and diabetes in community based subjects. In this study, 1,982 residents aged 30-79 years were enrolled from 2009 to 2012, and written informed consent was obtained. Serum resistin was measured by ELISA. SNPs were analyzed by TaqMan assays. Serum resistin was positively correlated with WBC count (r=0.31, P<0.0001). Precisely, serum resistin was mainly correlated with the neutrophil and monocyte counts (r=0.34, 0.19, both P<0.0001). Resistin SNP-420 and SNP-358 were not associated with WBC count and its components, whereas serum resistin was strongly determined by these SNPs (SNP-420 CC/CG/GG, n=853/885/228, WBC 5420/5401/5421 [×1000/µl, ANOVA P=0.96], resistin 9.3/13.4/17.9 [ng/ml, P<0.0001]; SNP-358 GG/GA/AA, n=1,213/667/89, WBC 5401/5434/5415 [P=0.88], resistin 9.2/16.0/23.7 [P<0.0001]). A multiple regression analysis showed that serum resistin was associated with total WBC, neutrophil, and monocyte counts after adjusted for age, sex, BMI, smoking, other metabolic risk factors, and SNP-420 and SNP-358. In summary, serum resistin was mainly associated with neutrophil and monocyte counts independent of resistin SNP-420 and SNP-358. Serum resistin appeared to be derived from WBC in humans. In Mexican Americans, the IRS1 G972R polymorphism (rs1801278) has been associated to such a marked reduction in glomerular filtration rate (GFR) (i.e. β=-13 ml/min/1.73 m2) to be considered a major determinant of kidney function. To study whether such strong effect can also be observed among individuals of European ancestry, we investigated a total of 3,973 White patients with type 2 diabetes. Standardized serum creatinine was measured by the modified kinetic Jaffè reaction and estimated GFR (eGFR) calculated by the MDRD formula; rs1801278 was genotyped by TaqMan assay. A nominally significant association was observed, with R972 carriers showing a modestly lower eGFR level as compared to other subjects (β=2.27 ml/min/1.73 m2, p=0.038). Our data indicate that IRS1 G972R is not as strong a determinant of GFR in diabetic patients of European ancestry as in Mexican Americans. Since we had 100% power to detect the previously reported association, the risk that our finding is a false negative one is minimal. Rather, our data does suggest that White diabetic patients carrying R972 variant have a modestly reduced GFR, thus pointing to IRS1 as a typical minor gene in the context of a multifactorial disease. Further studies are needed before the observed association is defined as established. The aim of our study was to investigate association between polymorphic markers (PM) of genes involved in production of vasoactive factors (NO, angiotensin II) and insulin secretion and/or sensitivity with development of chronic kidney disease (CKD) and obesity in type 2 diabetic (T2D) patients. We enrolled 444 T2D patients. PM I/D in ACE gene and ecNOS4a/4b in NOS3 gene were analyzed among 263 patients divided in 2 groups: with and without CKD (n=78/175) based on glomerular filtration rate (GFR) < and ≥ 60 ml/min/1.73m2 calculated by MDRD formula. PM in PPARG2, KCNJ11, TCF7L2 and SLC30A8 genes were analyzed among 181 patients which also were divided in 2 groups: with and without obesity (n=101/80) based on BMI ≥ 30 and < 30 kg/m². PM studied using PCR. Differences in alleles/genotypes frequencies were assessed by χ² and odds ratio (OR) were calculated. The main clinical parameters, such as age, sex, HbA1c, serum levels of cholesterol and triglycerides, blood pressure level were similar between all the groups. There were no association of CKD development with I/D in ACE gene, whereas we observed significant differences in alleles/genotypes distribution of ecNOS4a/4b in NOS3 gene between groups with and without CKD: the prevalence of allele 4b and genotype 4b/4b in patients without CKD: OR=0,45, 95%CI: 0,3-0,7 and OR=0,12, 95%CI: 0,02-0,9, respectively; while allele 4a and genotype 4a/4a did as risk factors: χ²=10,42; =0.001; OR=2,2, 95%CI: 1,4-3,6; genotype 4a/4a: χ²=10,28; =0.006; OR=2,21, 95%CI: 1,2-3,9. We also found an excess of genotype pro/pro of PPARG2 gene in group with obesity: 59% vs. 51%; OR = 1,27; 95%CI: 1,02-2,08. We conclude that T2D patients might have genetic susceptibility to CKD development caused by polymorphism ecNOS4a/4b in NOS3 gene with protective role of allele 4b and genotype 4b/4b; while obesity might be determined by polymorphism of PPARG2 gene with pro/pro genotype considered as a risk factor. 1673-P Deficiency of Urokinase Plasminogen Activator Linked to Development of Type 2 DM JIN-SHUEN CHEN, LI-CHIEN CHANG, CHUNG-ZE WU, TZU-LING TSENG, DEE PEI, NAIN-FENG CHU, Taipei, Taiwan, Hsinchu, Taiwan, New Taipei City, Taiwan, Taitung, Taiwan Urokinase plasminogen activator (uPA) not only triggers a proteolysis cascade, but is also linked to pleiotropic functions, such as the development of inflammatory and immune responses. In the present study, we examined whether uPA plays a role in the production of type 2 DM in mice and cell models as well as in a limited survey of clinical cases. In mice models, wild type (C) and uPA knockout (uPA-/-) mice were both fed a high-fat diet and treated with streptozotocin and nicotinamide for development of type 2 DM. For the development of type 2 DM, the success rate of development of type 2 DM was significantly higher in group uPA-/- than in group C. The group uPA-/mice treated with uPA plasmid showed resistance to developing type 2 DM, which was similar to the result of group C. Furthermore, in clinical cases, the plasma level of uPA in the obese children was significantly lower than in the thin group. Taken together, we suggest that low plasma uPA may be a risk factor for the production of type 2 DM. For the study of insulin resistance and secretion, in cell model, the NIT-1 β cell was treated by uPA siRNA, the rate of insulin secretion was significantly decreased compared to the cell line without treatment. In mice models, the HOMA-IR in group C and uPA-/both increased daily with the high-fat diet. The HOMA-β in group uPA-/- was significantly lower than in group C before induction. Furthermore, HOMA-β in uPA-/- mice was still low one month after induction, as compared with HOMA-β , which was restored slightly in group C, suggesting uPA-/- lacks the ability to regenerate β cells. Similarly, IHC stain of insulin in islet cells of wild type mice showed insulin particles increased one month after induction, but insulin particles in islet cell in uPA-/- mice were still fewer than those in the group C. In conclusion, uPA plays an important role in insulin secretion, β cell regeneration and development of type 2 DM. Supplement of uPA may delay development of type 2 DM, and offer one strategy for prevention and treatment of type 2 DM in the future. 1676-P Joint Effects of Known Type 2 Diabetes Susceptibility Loci in a Genome-Wide Association Study of Singaporean Chinese: The Singapore Chinese Health Study ZHANGHUA CHEN, MYRON D. GROSS, MARK A. PEREIRA, MARK SEIELSTAD, WOON-PUAY KOH, YIK-YING TEO, E. SHYONG TAI, JIANJUN LIU, KHAI KOON HENG, WEE YANG MEAH, XIAO YIN CHEN, CHANG HUA WONG, HONG BOON TOH, JIAN-MIN YUAN, DANIEL O. STRAM, Los Angeles, CA, Minneapolis, MN, San Francisco, CA, Singapore, Singapore, Pittsburgh, PA Supported by: NSC (100-2314-B-016-020) ADA-Funded Research & Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), but mostly among populations of European descent rather than ethnic groups with higher risk of diabetes. We tested whether For author disclosure information, see page 829. Guided Audio Tour poster A437 POSTERS ANNA ZHELEZNYAKOVA, OLGA VIKULOVA, SVETLANA SAVELEVA, VALERIY NOSIKOV, MARINA SHESTAKOVA, Moscow, Russian Federation Epidemiology/ Genetics 1675-P Polymorphisms in NOS3 and PPARG2 Genes Contribute to Genetic Susceptibility to the Development of Chronic Kidney Disease and Obesity in Type 2 Diabetic Patients IMMUNOLOGY CATEGORY the previously identified T2D single-nucleotide polymorphisms (SNPs) and SNPs found in regions near identified T2D SNPs were associated with T2D within the Singapore Chinese Health Study. Using an Affymetrix GW ASI SNP array, we successfully genotyped 507,509 SNPs in 4678 participants (2338 cases with physician-diagnosed T2D and 2340 controls with glycated hemoglobin < 6.0%). Imputation using 1000 genomes project data was conducted for a fine-mapping analysis. We selected 98 T2D-related SNPs (p<10 -5) from the NHGRI GWAS Catalog for replication. Forty-four SNPs were genotyped and 54 SNPs were imputed with r 2>0.80. Positive associations between counts of the reported risk allele and T2D status were found for 73 of the 98 T2D SNPs; of which 24 were significant (p<.05). Combining the reported risk alleles of the 98 SNPs into an unweighted risk score we estimated a relative risk per allele of 1.025 (p=7.5×10 -10). Individuals in the highest quintile of the risk allele distribution were at 1.6-fold greater risk (p=0.0001) of T2D compared with those in the lowest quintile. Conditional analysis was performed for SNPs within 50kb of an index GWAS SNP by fitting both the nearby and the GWAS SNPs in logistic regression. Several potentially novel independent associations (remaining significant after multiple correction) were indicated and may be reflecting new signals in some of the same regions containing already known T2D SNPs. In conclusion, we replicated many of the previously reported diabetes-related SNPs and their joint effects in Singaporean Chinese and identified potentially novel candidate SNPs that are associated with T2D risk in an ethnic group with a high risk of diabetes. Further replication of novel SNPs is planned. IMMUNOLOGY Guided Audio Tour: Immunometabolism (Posters: 1678-P to 1683-P), see page 19. & JEFFREY D. FELDSTEIN, STEPHEN N. DAVIS, JENNIFER WHITMORE, HANY ZAYED, Berkeley, CA, Baltimore, MD Inflammation of the beta cells allegedly leads to less insulin production and secretion. The new anti-interleukin-1β (IL-1β) monoclonal antibody, gevokizumab, was evaluated in patients with type 2 diabetes uncontrolled on metformin alone. In a parallel, double-blind, placebo-controlled phase II trial, 421 patients were randomly allocated to monthly subcutaneous injections of placebo or gevokizumab at doses of 0.01, 0.03, 0.1, or 0.3 mg/ kg for 6 months. There were no drug-related serious adverse events. Incidence of infection in the gevokizumab and placebo groups were comparable (26% vs 24%), with nasopharyngitis being the most frequent. The principal objective in terms of reduction of hemoglobin A1c, fasting plasma glucose, fasting proinsulin/ insulin ratio, or C peptide was not reached. In contrast, six months’ treatment with gevokizumab was associated with a rapid, prolonged, and significant decrease in high-sensitivity C reactive protein (hs-CRP) in all groups versus placebo (all p<0.02).Patients who were on RAAS modulators, statins or both had a similar sustained strong responsive decrease in hs-CRP. Gevokizumab, an IL-1β modulating antibody, had a marked antiinflammatory effect measured by hs-CRP. The significant observed decrease in inflammatory status demonstrated by a sharp extended decrease in hs-CRP in these patients may potentially have beneficial cardiovascular effects. The role of anti-inflammatory drugs in diabetes still needs to be demonstrated. Studies using cardiovascular end-points needs to be further evaluated. 1677-P Core Clock Gene Expression in Muscle and Adipose Tissue are Correlated With Metabolic Traits POSTERS BRIAN A. GRICE, MAXIMILIAN HOHENADEL, CLINTON C. MASON, JONATHAN KRAKOFF, ROBERT C. WILLIAMS, ROBERT L. HANSON, Phoenix, AZ Immunology/ Transplantation 1678-P Anti-Inflammatory Effect of Monthly Subcutaneous Gevokizumab in Subjects With Type 2 Diabetes Mellitus on Stable Metformin Circadian rhythm refers to biologic and metabolic processes with entrained 24 hour oscillations. We investigated whether mRNA expression levels of core clock genes in human adipose and muscle tissue are correlated with metabolic traits. Participants with biopsies were Pima Indians recruited for a study of the etiology of type 2 diabetes and when biopsied were non-diabetic, aged 18 years or older, healthy by medical examination and on no medications. Biopsies were performed fasting between 8 and 9 a.m. RNA expression from muscle (n=219) and adipose (n=209) tissue was measured using Affymetrix GeneChip Human Exon 1.0 array. In total we selected 12 core clock genes, represented by both Bass et al. (Science 2012) and Kegg Pathways, for analysis. Metabolic traits were percent fat (by DXA or underwater weighing), fasting and 2-hour plasma glucose, and insulin action (by euglycemic-hyperinsulinemic clamp). An F-test with 12 degrees of freedom was performed to test the null hypothesis of no association between the metabolic trait and expression of any of the clock genes. If we rejected the null hypothesis we considered a p<0.05 to be significant for trait expression correlations, otherwise significance after Bonferroni correction was p<0.004. Several clock genes were associated with metabolic traits (figure 1). These results indicate that the expression of clock genes may play a role in metabolism. 1679-P WITHDRAWN & 1680-P Elevated RBP4 Levels Cause Insulin Resistance by Activating Antigen-Presenting Cells (APCs) and Proinflammatory Responses in Adipose Tissue In Vivo PEDRO M. VIEIRA, MARK M. YORE, PETER DWYER, ISMAIL SYED, KERRY WELLENSTEIN, ODILE D. PERONI, BARBARA KAHN, Boston, MA Supported by: NIH RBP4, an adipocyte- and liver-secreted protein which is highly associated with insulin resistance, was recently shown to activate proinflammatory pathways. We aimed to determine the mechanism for RBP4-induced & For author disclosure information, see page 829. A438 Guided Audio Tour poster ADA-Funded Research