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Supplement issue Unmet Needs in Hispanic/Latino Patients with Type 2 Diabetes Mellitus Kenneth Cusi, MD,a and Gloria L. Ocampo, MDb a The University of Florida at Gainesville, Gainesville, Florida, USA, and bUniversity of Texas Health Science Center, San Antonio, Texas, USA ABSTRACT In the United States, the prevalence of adults who are overweight or obese is higher in Hispanics/Latinos compared with non-Hispanic whites. In addition, data from the National Health and Nutrition Examination Survey (NHANES) indicate that the prevalence of type 2 diabetes mellitus is consistently greater in racial/ethnic minority groups, such as Hispanics/Latinos, compared with non-Hispanic whites. In fact, data from the Centers for Disease Control and Prevention (CDC) from 2007 to 2009 suggest that the prevalence of type 2 diabetes is almost twice as high in Hispanics/Latinos compared with non-Hispanic whites (11.8% vs. 7.1%, respectively). Although genetics plays a role in the increased prevalence of type 2 diabetes in Hispanics/Latinos, cultural and environmental factors also contribute. In addition to the increased prevalence of type 2 diabetes in Hispanics/Latinos, evidence suggests that the patients in this population are often undertreated and, therefore, less likely to achieve control of their glucose, blood pressure, and lipid levels. Because individuals with type 2 diabetes have a 2- to 4-fold increased risk of cardiovascular disease compared with individuals with normal glucose levels, there is consensus that targeting environmental factors, particularly the development of obesity at an early age, is the most cost-effective approach to prevent the development of type 2 diabetes and its broad spectrum of complications, including cardiovascular disease. Cultural and socioeconomic barriers, such as language, cost, and access to goods and services, must be overcome to improve management of type 2 diabetes in this high-risk population. By increasing healthcare provider awareness and the availability of programs tailored to Hispanic/Latino individuals, the current treatment gap among ethnic minorities in the United States will progressively narrow, and eventually, disappear. © 2011 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2011) 124, S2–S9 KEYWORDS: Culture; Hispanic; Latino; Type 2 diabetes mellitus; Unmet needs The metabolic syndrome is frequently used to define a cluster of risk factors (central obesity, high triglyceride/low high-density lipoprotein cholesterol levels, hypertension, and elevated plasma glucose levels) that increase the risk of developing cardiovascular disease.1 Evidence suggests that its presence increases healthcare utilization and costs compared with patients without this condition, with average annual costs increased 1.6 times for patients with the metabolic syndrome compared with those without it (mean cost in 2005 US dollars, $5,732 vs. $3,581).2 In the United States, healthcare expenditures for obesity-related condiStatement of author disclosure: Please see the Author Disclosures section at the end of this article. Requests for reprints should be addressed to Kenneth Cusi, MD, Chief, Endocrinology and Diabetes Division, The University of Florida at Gainesville, 1600 SW Archer Rd., Room H-2, Gainesville, Florida 32610-0226. E-mail address: [email protected]. 0002-9343/$ -see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2011.07.017 tions were estimated to be approximately $168 billion, or approximately 17% of total healthcare costs based on data collected from 2000 to 2005.3 In the United States in 2007 to 2008, almost one third of children aged 2 to 19 years (31.7%)4 and approximately two thirds of adults (68.0%)5 were overweight or obese. Obesity is increasing at alarming rates in the United States, particularly in Hispanics/Latinos and African American women as well as socially disadvantaged groups.6 Similarly, diabetes mellitus is a substantial healthcare burden in the United States; in 2007, costs associated with diabetes were estimated at $174 billion.7 By 2030, it is estimated that approximately 30 million Americans will have diabetes.8 There is a strong ethnic component to both the metabolic syndrome and type 2 diabetes mellitus, with non-Caucasian (non-white) populations having an increased prevalence.9,10 The prevalence of the metabolic syndrome is 1.5 times Cusi and Ocampo Unmet Needs in Hispanic/Latino Patients with Type 2 Diabetes Figure 1 Age-adjusted prevalence of metabolic syndrome (defined as a collection of risk factors that increase a person’s risk of developing cardiovascular disease)1 by sex and ethnicity among adults aged ⱖ20 years in the National Health and Nutrition Examination Survey (NHANES): United States, 2003–2006.11 higher in Mexican American females living in the United States compared with non-Hispanic white females (odds ratio, 1.55; 95% confidence interval [CI], 1.06 to 2.29); however, the prevalence of the metabolic syndrome is not significantly different between Mexican American and nonHispanic white males (Figure 1).11 In addition, the prevalence of adults who are overweight or obese is higher among Hispanics/Latinos compared with non-Hispanic whites,5 as is the prevalence of type 2 diabetes9,12 and prediabetes.12 The American Diabetes Association (ADA) has estimated that 79 million adults in the United States have prediabetes, including one third of adults aged ⬎60 years, which puts them at high risk for developing type 2 diabetes.13 Prediabetes is defined as impaired fasting glucose (based on a fasting plasma glucose [FPG] level of 100-125 mg/dL [1 mg/dL ⫽ 0.05551 mmol/L]) and/or impaired glucose tolerance (IGT; based on a 2-hour postprandial glucose level of 140-199 mg/dL as measured during an oral glucose tolerance test [OGTT]).14 Recently, a hemoglobin A1c (HbA1c) level of 5.7% to 6.4% has been included in the definition of prediabetes.14 It is important to realize that Hispanics/Latinos are much more predisposed to develop prediabetes compared with non-Hispanic whites, and that individuals with prediabetes have a 1.5-fold increased risk of cardiovascular disease compared with people with normal glucose levels. Furthermore, individuals with type 2 diabetes have a 2- to 4-fold increased risk of cardiovascular disease. THE METABOLIC SYNDROME IN HISPANIC/LATINO PATIENTS The hallmarks of the metabolic syndrome are obesity, dyslipidemia, hypertension, and hyperglycemia, against a back- S3 ground of insulin resistance. The prevalence of the metabolic syndrome by sex and race/ethnicity, according to data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2006, is summarized in Figure 1.11 The prevalence of individual metabolic abnormalities in Mexican Americans according to sex is presented in Figure 2. Generally, NHANES data showed that Mexican Americans had an increased prevalence of dyslipidemia compared with non-Hispanic whites and non-Hispanic blacks; however, increases in abdominal obesity in Mexican Americans varied according to sex. In males, all of these abnormalities (high FPG, increased triglycerides, low high-density lipoprotein cholesterol levels) were shown to have a higher prevalence in Mexican Americans compared with non-Hispanic whites or non-Hispanic blacks, with the exception of abdominal obesity, which was higher in non-Hispanic whites, and hypertension/use of antihypertensive agents, which showed a trend to be higher in non-Hispanic whites and was significantly higher in non-Hispanic blacks (P ⬍0.05 vs. Mexican Americans; Figure 2).11 In contrast, in females the prevalence rate of abdominal obesity was similar in Mexican Americans compared with non-Hispanic blacks and the prevalence rate of hypertension/use of antihypertensive agents was similar compared with non-Hispanic whites; however, all other parameters were higher in Mexican American females compared with their non-Hispanic white counterparts (Figure 2).11 When general obesity (as measured by body mass index [BMI] rather than abdominal obesity) is considered, Hispanics/Latinos have a higher prevalence of obesity compared with non-Hispanic whites. Based on NHANES data from 2007 to 2008, there was a higher prevalence of obesity in Hispanic/Latino men and women (34.3% and 43.0%, respectively) compared with non-Hispanic white men and women (31.9% and 33.0%).5 Similarly, the prevalence of obesity in Hispanic/Latino adolescents (12 to 19 years of age) was higher than in non-Hispanic whites (BMI ⱖ95th percentile: 21.7% vs. 15.6%, respectively).4 TYPE 2 DIABETES MELLITUS IN HISPANIC/LATINO PATIENTS Comparison of NHANES data from 1988 to 2006 show that the prevalence of diagnosed type 2 diabetes increased significantly over time, and that minority groups had a consistently higher prevalence of both diagnosed and undiagnosed type 2 diabetes compared with non-Hispanic whites.12,15 According to Centers for Disease Control and Prevention (CDC) data from 2007 to 2009, the prevalence of type 2 diabetes in persons aged ⱖ20 years was almost twice as high in Hispanics/ Latinos compared with non-Hispanic whites (11.8% vs. 7.1%, respectively).13 As mentioned earlier, the presence of prediabetes increases the risk of developing type 2 diabetes. NHANES data from 1984 to 2000 show that the lifetime risk of developing type 2 diabetes for Hispanics/Latinos born in the United States in S4 The American Journal of Medicine, Vol 124, No 10S, October 2011 Figure 2 Prevalence of metabolic abnormalities in adults aged ⱖ20 years according to sex and ethnicity. BP ⫽ blood pressure; FPG ⫽ fasting plasma glucose; HDL-C ⫽ high-density lipoprotein cholesterol; TGs ⫽ triglycerides.11 2000 is 45.4% (men)/52.5% (women); overall, this analysis indicates that Hispanics/Latinos have the highest lifetime risk for type 2 diabetes compared with other racial/ethnic groups.16 A recent analysis from the CDC found that the percentage of adults in the United States aged ⱖ20 years with prediabetes (using either FPG or HbA1c for diagnosis) in 2005 to 2008 was similar for non-Hispanic whites (35%), non-Hispanic blacks (35%), and Mexican Americans (36%) after adjusting for population age differences.13 However, it should be noted that an OGTT, the “gold standard” for diagnosing type 2 diabetes, was not used for this analysis, which could explain why Hispanics/ Latinos and other ethnic minorities had a higher prevalence of type 2 diabetes despite apparently similar rates of prediabetes. Based on the latter observation, recent treatment guidelines have acknowledged the increased risk among ethnic minorities. Guidelines from both the American Association of Clinical Endocrinologists (AACE) and the ADA include Hispanic/Latino ethnicity as a risk factor for prediabetes and type 2 diabetes and support priority screening for these populations.14,17 Cusi and Ocampo Unmet Needs in Hispanic/Latino Patients with Type 2 Diabetes Figure 3 S5 Genetic and acquired factors that can cause metabolic abnormalities. METABOLIC ABNORMALITIES IN HISPANIC/ LATINO PATIENTS WITH TYPE 2 DIABETES MELLITUS The “thrifty gene” hypothesis proposes that insulin resistance was a mutation that became imprinted on the genome because it conferred a survival advantage during periods of famine, allowing individuals to store adipose tissue and thereby survive longer than those without the mutation. However, now that food supplies are more abundant, certain populations that carry this mutation are predisposed to conditions such as type 2 diabetes.18,19 The resultant insulin resistance and obesity-related metabolic complications create a constellation of cardiovascular risk factors, as observed in the metabolic syndrome and type 2 diabetes, that are more frequently found in Hispanic/Latino populations. The metabolic abnormalities of type 2 diabetes are believed to be caused by both genetics and environmental factors (Figure 3).20 While the genetics of type 2 diabetes in Hispanics/Latinos are poorly understood,21 there is consensus that targeting environmental factors, particularly the development of obesity at early stages, is the most costeffective approach to prevent the development of the disease and its broad spectrum of micro- and macrovascular complications. The development of obesity and type 2 diabetes in Hispanics/Latinos, as well as in other ethnic minorities, is not only related to genetically determined ethnic susceptibility but also linked to the impact of migration and the effects of urbanization, mechanization, nutrition transi- tion, physical inactivity, stress, and other poorly defined factors.22 Insulin resistance is a well-known precursor to type 2 diabetes. Although insulin resistance can be caused by obesity,23 studies suggest that insulin resistance in Hispanics/ Latinos is caused by a combination of environmental and genetic factors.18,21,24 In general, Hispanics/Latinos have a higher level of insulin resistance compared with non-Hispanic whites, and ethnicity has been shown to be an independent correlate of insulin resistance after adjustment for BMI, age, and presence of type 2 diabetes.25 The Insulin Resistance Atherosclerosis Study (IRAS) demonstrated that both insulin resistance and -cell dysfunction predicted conversion to type 2 diabetes in all ethnic/racial groups evaluated—Hispanics/Latinos, African Americans, and non-Hispanic whites.26 However, Hispanics/Latinos have a higher rate of conversion from prediabetes to type 2 diabetes than nonHispanic whites; in the general population of the United States, about 5% to 10% of patients with prediabetes are believed to convert to type 2 diabetes annually, but this figure may be as high as 15% in Hispanics/Latinos.27 In the Diabetes Prevention Program (DPP), the overall conversion rate was 11%, similar to that reported for Hispanics/Latinos (11.7%).28 In a 10-year follow-up of the DPP, event rates ranged from approximately 5% to 7%.29 In the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) study, the progression from IGT to type 2 diabetes was 6.5% in patients with a BMI ⬍28 kg/m2 but as high as 10.2% in patients with a BMI ⱖ33 kg/m2.30 S6 The American Journal of Medicine, Vol 124, No 10S, October 2011 Notably, a proportional hazards analysis of these patients found no significant increase in the progression to type 2 diabetes or death for the Hispanic/Latino population compared with the European population for either the unadjusted risk (hazard ratio [HR], 1.25; 95% CI, 0.95 to 1.65) or the risk adjusted for baseline differences in age, sex, waist– hip ratio, BMI, geographic region, and average annual weight change (HR, 1.26, 95% CI, 0.89 to 1.80).31 Hispanic/Latino individuals also have a tendency to develop abdominal obesity, which, as well as being linked to insulin resistance, is associated with endothelial dysfunction and vascular inflammation.32-34 In the San Antonio Heart Study, predictors of type 2 diabetes included both waist circumference and BMI, suggesting that the increased risk of type 2 diabetes in Hispanics/Latinos may be related to a greater amount of visceral fat and overall obesity.35 Endothelial dysfunction and subclinical inflammation contribute to the development of both type 2 diabetes and cardiovascular disease, with evidence suggesting links between a proinflammatory environment and altered glucose homeostasis and atherogenesis (reviewed by Sjöholm and Nyström36). A study of Hispanic/Latino children and adolescents that compared lean and obese individuals without type 2 diabetes found that those who were overweight had elevated levels of markers associated with endothelial dysfunction and inflammation, such as tumor necrosis factor–␣, tissue plasminogen activator, and C-reactive protein, compared with lean individuals; the increase in these markers was closely related to body fat and insulin resistance, suggesting that obese children may be at higher risk of developing type 2 diabetes and cardiovascular disease compared with lean children.37 Overweight Hispanic/Latino youth with the metabolic syndrome are significantly more insulin resistant, compared with those without the syndrome. The adipocytederived hormone adiponectin may be an important predictive marker for the metabolic syndrome. Hispanic/Latino children with type 2 diabetes have significantly lower adiponectin levels compared with children without the disease (P ⬍0.05).38 Adiponectin has also been independently reported to predict the metabolic syndrome in overweight Hispanic/Latino youth.38 Hispanic/Latino persons generally appear to have higher triglyceride levels than non-Hispanic whites, and there is some evidence suggesting a genetic basis.39 In a study of 173 Hispanic/Latino and African American youth, Hispanics/Latinos had a significantly higher triglyceride level compared with African Americans (113 mg/dL vs. 72 mg/dL [1 mg/dL ⫽ 0.01129 mmol/L], respectively; P ⬍0.001).40 Similarly, triglyceride levels were highest in Hispanics/ Latinos compared with non-Hispanic whites and African Americans in IRAS (n ⫽ 1,625; 148 mg/dL, 134 mg/dL, and 102 mg/dL, respectively; P ⬍0.001)41 and in NHANES data from 1999 to 2002 (n ⫽ 2,804; 144 mg/dL, 140 mg/dL, and 99 mg/dL, respectively).42 In contrast, a retrospective chart review of 6,450 patients from a single center showed that Hispanic/Latino patients had a 42% lower risk of having abnormal triglyceride levels compared with white pa- tients.43 It may be that these differing results are owing to differences in study populations. Evidence indicates that Hispanic/Latino patients with type 2 diabetes are at greater risk for microvascular complications associated with this disease (reviewed in Umpierrez et al44). For example, NHANES data from 1988 to 1994 for patients with type 2 diabetes who were ⱖ40 years of age found that the prevalence of diabetic retinopathy was 84% greater in Mexican Americans compared with non-Hispanic whites.45 Furthermore, after adjustment for duration of type 2 diabetes, HbA1c level, and antidiabetes treatment (insulin versus oral agents), the risk of retinopathy in Mexican Americans remained twice that of non-Hispanic whites.45 Renal complications also appear to be increased in Hispanic/Latino patients with type 2 diabetes compared with nonHispanic white patients. A large, longitudinal observational study (n ⫽ 62,432) reported that the incidence of end-stage renal disease was approximately 40% greater in Hispanic/ Latino patients with type 2 diabetes compared with nonHispanic white patients.46 Although the incidence of microvascular complications is higher in Hispanics/Latinos compared with non-Hispanic whites, evidence from the San Luis Valley Diabetes study suggests that cardiovascular disease mortality was equal or lower in Hispanic/Latino patients compared with non-Hispanic white patients (8.8/ 1,000 vs. 12.9/1,000 person-years, respectively).47 ACHIEVEMENT OF TREATMENT TARGETS IN HISPANIC/LATINO PATIENTS In general, data suggest that Mexican Americans with metabolic risk factors are undertreated and less likely to achieve control. In NHANES (1999 to 2002), the percentage of Mexican Americans being treated (42% vs. 61%; P ⱕ0.001) and achieving control (blood pressure ⬍140/90 mm Hg; 49% vs. 58%; P ⱕ0.05) was significantly lower compared with non-Hispanic whites.48 NHANES data from 1999 to 2002 also demonstrated that, although the prevalence of dyslipidemia was slightly lower in Mexican Americans compared with non-Hispanic whites (31% vs. 35%, respectively; P ⱕ0.05), Mexican Americans received less treatment for dyslipidemia (14% vs. 30%; P ⱕ0.001).48 Consistent with these findings, the Multi-Ethnic Study of Atherosclerosis (MESA) reported the prevalence of dyslipidemia to be slightly lower and to be undertreated when comparing Hispanics/Latinos with non-Hispanic whites.49 In MESA, 32% of Hispanic/Latino men and 27% of Hispanic/Latino women had dyslipidemia compared with 37% and 24% of non-Hispanic white men and women, respectively, and Hispanic/Latino patients were approximately 20% less likely to receive pharmacologic treatment for dyslipidemia. As a result, control rates were lower in Hispanic/Latino men (69%) and women (75%) compared with non-Hispanic men (76%) and women (86%).49 Similarly for blood pressure and dyslipidemia, Hispanic/ Latino patients are less likely than non-Hispanic white patients to achieve recommended HbA1C treatment targets. Cusi and Ocampo Unmet Needs in Hispanic/Latino Patients with Type 2 Diabetes Historically, Hispanics/Latinos in the United States are considered to be a genetic mix of Native American, black, and Spanish ancestry, and their risk of developing type 2 diabetes is dependent on the specific mix of genes inherited; for example, those who have a higher proportion of Native American genes have a higher risk of developing type 2 diabetes.50,51 Kirk and colleagues52 examined differences in the treatment of minority patients with type 2 diabetes by comparing data from African American, Hispanic/Latino, American Indian, and Asian/Pacific Islander populations with that from non-Hispanic white populations (data from 78 studies were included in this analysis). Overall, Hispanics/ Latinos had poorer outcomes for control of hyperglycemia, as well as hyperlipidemia (defined as elevated low-density lipoprotein cholesterol) and hypertension. In all 8 studies that evaluated glycemic control specifically in Hispanic/ Latino patients with type 2 diabetes, mean HbA1c was higher in the Hispanic/Latino population compared with the white population. Although the disparities between Hispanics/ Latinos and non-Hispanic whites were most pronounced with regard to glycemic control, low-density lipoprotein cholesterol levels and blood pressure were also less controlled.52 Based on NHANES data from 1999 to 2006, an HbA1c level of ⬍7.0% was achieved by only 37.8% of Hispanic/Latino patients with type 2 diabetes born in the United States compared with 58.1% of non-Hispanic white patients (P ⬍0.001).53 Furthermore, the disparity between the percentage of Hispanic/Latino and non-Hispanic patients achieving an HbA1c level of ⬍7.0% continued to increase from 1999 to 2006. Similar to trends observed for glycemic control, blood pressure control rates (⬍140/90 mm Hg) were also significantly lower for Hispanics/Latinos than for non-Hispanic whites (42.5% vs. 52.8%, respectively; P ⫽ 0.005).53 A recent study54 reported similar trends to the McWilliams et al53 study in terms of glycemic control, with Mexican Americans less likely than whites to achieve an HbA1c level of ⬍7.0%. Barriers to the achievement of treatment goals include cultural and socioeconomic factors such as language, cost, and access to goods and services.55 For instance, a study in 18,510 non-Hispanic white patients and 2,078 Hispanic/ Latino patients found that the latter were less likely to receive appropriate type 2 diabetes quality of care and to self-monitor their disease, including measurement of HbA1c, foot check by healthcare provider, dilated eye exam, influenza and pneumococcal immunizations, type 2 diabetes education, and self-monitoring of feet and blood glucose.56 Ethnic/racial disparities for HbA1c testing and foot exams persisted even after controlling for access to care, socioeconomic status, and demographics. Evidence suggests that the use of culturally sensitive education programs can improve type 2 diabetes outcomes in the Hispanic/Latino patient population.55,57,58 Liebman and associates57 implemented self-management activities in Hispanics/Latinos over a course of 3 years using bilingual (Spanish/English) multisession activities, including formal type 2 diabetes education classes, exercise, and chronic S7 disease self-management classes. Nearly half of the participants achieved an HbA1c level of ⬍7.0%, and fewer had markedly elevated HbA1c levels.57 More recently, Castillo and colleagues58 reported that the use of community health workers in Hispanic/Latino communities is helpful in teaching basic type 2 diabetes management skills, delivered in short 2-hour classes over 10-week programs, that have a positive impact on glucose and blood pressure control. SUMMARY The Hispanic/Latino population in the United States has a greater prevalence of metabolic abnormalities and type 2 diabetes compared with non-Hispanic whites. Compared with non-Hispanic whites, Hispanics/Latinos tend to be generally more obese, and are less likely to achieve control of parameters such as HbA1c, blood pressure, and lipid levels. Overall, the magnitude of the problem of type 2 diabetes in Hispanics/Latinos is large, worrisome, and getting worse. Some of the ethnic differences in prevalence between Hispanics/Latinos and whites have a genetic basis, but socioeconomic and cultural factors have a greater influence. To achieve treatment goals, healthcare providers must understand the spectrum of socioeconomic and cultural factors affecting Hispanics/Latinos. Recent studies in a variety of settings clearly demonstrate that type 2 diabetes education programs specifically tailored to the Hispanic/Latino patient frequently yield significant success. We envision that with greater healthcare provider awareness and wider availability of programs tailored to Hispanic/Latino individuals, the current treatment gap among ethnic/racial minorities in the United States will progressively narrow, and eventually, disappear. ACKNOWLEDGMENTS Medical writing services and editorial assistance provided by Sheridan Henness, PhD, Karen Stauffer, PhD, and Lucy Whitehouse, of inScience Communications, a Wolters Kluwer business, were funded by Daiichi Sankyo, Inc. AUTHOR DISCLOSURES The authors who contributed to this article have disclosed the following industry relationships: Kenneth Cusi, MD, has served as a consultant to Daiichi Sankyo, Inc., Merck & Co., Inc., and Schering-Plough Corporation (now Merck). Gloria L. Ocampo, MD, has served as a consultant to Daiichi Sankyo, Inc. References 1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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