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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015 An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients: Looking at Diabetes Medications with a Cardiologist’s Eye Part 1 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000 Lecture Based on Evidence-Based PRACTICE Has Led to Students/MDs who dont ThinkEg: if no evidence, continue doing same old dangerous therapy (SU); Specialists are abrogating their responsibility to evaluate and lead in use of new medications, processes of care EBM=Evidence = Based Medicine + EBM=Evidence Based Medicine Research Evidence Randomized, Prospective Publication Trials Critical Appraisal + Patient-Based Experience Clinical expertise Expert Opinions Guidelines = Evidence Based Practice Duggal, Evidence-Based Medicine in Practice,, Int’l j. Clinical Practice,65:639-644,2011 Allan D. Sniderman, MD; Kevin J. LaChapelle, MD; Nikodem A. Rachon, MA; and Curt D. Furberg, MD, PhDMayo Clin Proc The Necessity for Clinical Reasoning in the Era of Evidence-Based Medicine October 2013;88(10):1108-1114 Trisha Greenhalgh et al, Evidence based medicine: a movement in crisis? BMJ 2014; 348 Natural History of Type 2 Diabetes Age 0-15 Genes 15-40+ 15-50+ 25-70+ Envir.+ Other Disease Macrovascular Complications Insulin Resistance Obesity (visceral) IR phenotype Poor Diet Inactivity Atherosclerosis obesity hypertensionHDL,TG, HYPERINSULINEMIA MI CVA Amp Endothelial dysfunction pp>7.8 PCO,ED Beta Cell Secretion Risk of Dev. Complications Disability IGT ETOH BP Smoking Eye Nerve Kidney DEATH Type II DM Blindness Amputation CRF Disability Microvascular Complications Pathogenic, β-CELL-CENTRIC Construct for All Diabetes Implications for Classification, Diagnosis, Prevention, Therapy, Research E P I G E N I T I C S Environmental Inflam. Triggers eg: viral,endocrine disruptors, food AGE’s, BIOME Resistance (obesity) inflammatory adipokines Polygenic- Gene E P I G E N I T I C S Inflammatory; Abnormal Immune Modulation other Monogenic (HLA) Polygenic Monogenic - MODY β-Cell PHENOTYPE secretion/mass − Mitochondrial Resistance-(obesity)FFA Poor diet, inactivity endocrine disruptors, food AGE’s ,BIOME Environmental Triggers Non Inflammatory Why Bother to Treat Agressively? From: Trends in Prevalence and Control of Diabetes in the United States, 1988– 1994 and 1999–2010 Trends in Prevalence and Control of Diabetes in the United States Figure Legend: Prevalence of total confirmed diabetes and obesity. Data from U.S. adults aged ≥20 y in NHANES 1988–1994, 1999–2004, and 2005–2010. Total confirmed diabetes was defined as diagnosed diabetes or undiagnosed diabetes with diagnostic levels of both hemoglobin A1c (≥6.5%) and fasting glucose (7.0 mmol/L [≥126 mg/dL]). Obesity was defined as body mass index ≥30 kg/m2; 601 persons were missing body mass index data. Prevalence estimates for total confirmed diabetes and obesity were obtained using only the subsample of participants who attended the morning fasting session (7385 participants for 1988–1994, 5680 participants for 1999–2004, and 6719 participants for 2005–2010). The midpoint for obesity prevalence between 1988–1994 and 1999–2004 was calculated as the average of the prevalence of the 2 periods. NHANES = National Health and Nutrition Examination Survey. Ann Intern Med. 2014;160(8):517-525. doi:10.7326/M13-2411 Date of download: 4/17/2014 One third of adults with diabetes are undiagnosed ~10% of US adults have diabetes/~20 million persons in 2005 Nearly one third dont know they have diabetes 26% of US adults have impaired fasting glucose (IFG)* Total: 35% of US adults with diabetes or IFG ~73.3 million persons *100–125 mg/dL Cowie CC et al. Diabetes Care. 2006;29:1263-8. NIDDK. National Diabetes Statistics. www.diabetes.niddk.nih.gov. RISK OF UNRECOGNIZED HYPERGYCEMIA: Effect of Hyperglycemia on Mortality, LOS, ICU admission, D/C Disposition FBS>126 Ppg>200 New Hyperglycemia Known Diabetes Normo-Glycemia #495 (26%) #1168 #223 (12%) Mortality, total 16 3 Mortality, ICU 31 11 Mortality, non-ICU 10 1.7 0.8 9 5.5 4.5 LOS ICU Admission 1.7 10 29 14 9 Home 56 74 84 Transition Care 20 15 10 Nursing Home 8 9 4 D/c Dispo. Umpierrez, JCEM 2002;87:978 Considering the Epidemic of Metabolic Syndrome, Prediabetes, Prevention Data, Undiagnosed Diabetes- ER Office and Pre-Admission IDENTIFICATION IS CRITICAL! • Family history: whether parents or siblings have had diabetes • Obesity: especially with an increase in abdominal girth • High-risk ethnic group: African Americans, Hispanics, Native Americans, Asians, and Pacific Islanders • Age: we’re looking at all ages, if patient seems at risk • Impaired fasting glucose or impaired glucose tolerance • Hypertension: blood pressure ≥ 140/90 mm Hg in adults • High density lipoproteins < 35 mg/dL or triglyceride levels ≥ 250 mg/dL • Gestational diabetes or given birth to an infant weighing > 9 pounds • Pre-adm , pre-cath, pre-op , pre-CABG FBS >100, ppg >140, POC HgA1c >6.0 Hyperglycemia Leads to Complications: May Be Present Prior to Diagnosis Hyperglycemia Spike (+variability) PPG Argument for Early Discovery Pre-diabetes, Early Treatment, Determine on Hospital Admission Acute toxicity Continuous A1C Chronic toxicity Tissue lesion Diabetic complications Microvascular Retinopathy Nephropathy Macrovascular Neuropathy PVD MI Stroke American Diabetes Association. 10 At: http://www.diabetes.org/diabetes-statistics/complications.jsp. Brownlee M. Diabetes mellitus: theory and practice. Elsevier Science Publishing Co., Inc; 1990:279-291. Ceriello A. Diabetes. 2005;54:1-7.