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Diabetes Mellitus 101 for Medical Professionals

Learn about the aggressive pathophysiologic approach to cardiometabolic therapy for type 2 diabetes, including risk factors, complications, and the importance of early detection and treatment.

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Diabetes Mellitus 101 for Medical Professionals

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  1. Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Part 1 Stanley Schwartz, MD, FACE, FACP Emeritus, Clinical Associate Professor of Medicine, University of Pennsylvania Affiliate, Main Line Health System, Wynnewood, Pennsylvania stschwar@gmail.com 6105472000

  2. Natural History of Type 2 Diabetes Age 0-15 15-40+ 15-50+ 25-70+ Envir.+ Other Disease Genes Macrovascular Complications Obesity (visceral) Poor Diet Inactivity IR phenotypeAtherosclerosisobesityhypertensionHDL,TG, HYPERINSULINEMIA Endothelial dysfunctionPCO,ED Disability Insulin Resistance MICVAAmp pp>7.8 DEATH IGT Type II DM  Beta Cell Secretion BlindnessAmputationCRF EyeNerveKidney Risk of Dev. Complications ETOHBPSmoking Disability Microvascular Complications

  3. Natural History of Type 2 Diabetes Age 0-15 15-40+ 15-50+ 25-70+ Envir.+ Other Disease Genes Macrovascular Complications Obesity (visceral) Poor Diet Inactivity IR phenotypeAtherosclerosisobesityhypertensionHDL,TG, HYPERINSULINEMIA Endothelial dysfunctionPCO,ED Disability Insulin Resistance MICVAAmp pp>7.8 DEATH IGT Type II DM  Beta Cell Secretion BlindnessAmputationCRF EyeNerveKidney Risk of Dev. Complications ETOHBPSmoking Disability Microvascular Complications

  4. Why Bother to Treat Agressively?

  5. One third of adults with diabetes are undiagnosed ~10% of US adults have diabetes/~20 million persons in 2005 Nearly one third don’t 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 Cowie CC et al. Diabetes Care. 2006;29:1263-8. NIDDK. National Diabetes Statistics. www.diabetes.niddk.nih.gov. *100–125 mg/dL

  6. 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

  7. Hyperglycemia Leads to Complications:Risk Starts with Pre-Diabetes Hyperglycemia Spike Continuous PPG A1C Chronic toxicity Acute toxicity Tissue lesion Diabetic complications (Brownlee hypothesis) Microvascular Macrovascular MI Stroke Retinopathy Nephropathy Neuropathy PVD 21% 18% 12% % of pts. with complication at DX 60% ASVD American Diabetes Association. 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. 9

  8. RISK OF UNRECOGNIZED HYPERGYCEMIA: Effect of Hyperglycemia on Mortality, LOS, ICU admission, D/C Disposition Umpierrez, JCEM 2002;87:978

  9. Metabolic Sydrome, IGT, Diabetes, CV Disease 1. Beginning at 83 mg/dL, rising 2-hr pp glucose levels correlated linearly with CHD mortality 2. Even mild glucose elevations (fbs >110) increase mortality in patients undergoing PCI 3. Almost 70% of patients with first MI have IGT or undiagnosed diabetes 4. In multiple studies stress hyperglycemia in AMI is associated with 3-10 x mortality risk in patients without known diabetes 5. In a group of >31,000 patients without known diabetes but with CV disease (CVD), patients, an 18 mg/dL-higher FPG was associated with a 23% increase in the risk of hospitalization for HF 6. Inc mortality in hosp if admitted wth CVA

  10. Cardiovascular disease and diabetes No A1C threshold is apparent Finnish study by Kuusisto et al; UKPDS epidemiologic analysis; EPIC-Norfolk Study ~65% of deaths are due to CV disease Cardiovascular complications of T2DM Coronary heart disease deaths2- to 4-fold Stroke risk 2- to 4-fold Impaired glucose tolerance (IGT) and postprandial hyperglycemia are CV risk factors Funagata Diabetes Study; Honolulu Heart Program; DECODE Study; Rancho Bernardo Study Heart failure 2- to 5-fold Bell DSH. Diabetes Care. 2003;26:2433-41. Centers for Disease Control (CDC). www.cdc.gov. T2DM = type 2 diabetes mellitus

  11. A1C Predicts Coronary Heart Disease in Type 2 Diabetes 30 28.4 Men Women 25 21.9 20 CHD events (events/100 persons) 16.7 16.2 15.7 15 10.2 9.6 10 8.7 7.3 6.4 5 3.8 3 2.1 1.7 0 <5.0% 5.0%- 5.5%- 6.0%- 6.5%- ³7.0% Known 5.4% 5.9% 6.4% 6.9% diabetes A1C concentration* *P<0.001 for linear trend across A1Ccategories. Khaw KT et al. Ann Intern Med. 2004;141:413-420.

  12. High Risk of Cardiovascular Events in Type 2 Diabetes 50 45 40 35 30 25 20 15 10 5 0 No diabetes Type 2 diabetes 7-year incidence of cardiovascular events (%) - + - + - + - + - + - + Prior myocardial infarction Stroke Cardiovascular deaths Myocardial infarction Haffner, NEJM 1998, 229-234

  13. THE PREVALENCE OF CHRONIC ANGINA POSES A SIGNIFICANT BURDEN TO THE US HEALTH CARE SYSTEM New Cases of Stable Angina Per Year (Among Americans ≥45 Years of Age) • ~16 million Americans have CHD • ~9.1 million Americans have angina pectoris 500,000 new cases are reported annually • Mean angina frequency is ~2 episodes per week > 18 million episodes each week or ~30 episodes each second Incidence (# of New Cases) 500,000 320,000 180,000 Men Women Total American Heart Association. Heart Disease and Stroke Statistics, 2008 Update. Pepine CJ, et al. Am J Cardiol. 1994;74:226-231.

  14. SEVERITY OF ANGINA SYMPTOMS PREDICTS POOR SURVIVAL MORTALITY IN VA PATIENTS (N=8900) WITH CAD After adjustment for potential confounders, greater physical limitation due to angina was associated with increased risk of death compared with patients with little or no limitation Years 0 1 2 3 4 1 Little to no limitation 75-100 Mild limitation: 27% higher risk of death 50-74 25-49 Moderate limitation: 61% higher risk of death *p<0.001 for log-ranktest for equality ofsurvivor function 0.74 Greatest limitation: 2.5 fold higher risk of death 0-24 0 Survival According to Physical Limitation Due to Angina (Seattle Angina Questionnaire Score) Mozaffarian D, et al. Am Heart J. 2003;146:1015-1022.

  15. Pathophysiology of Diabetic Complications: Implications for Goals of Therapy Epidemiology Hyperglycemia is a continuous Risk Factor No A1C threshold is apparent Worse >A1C, longer duration DM II Individual Susceptibility Genetic/ethnic ?Acquired IV Early I Metabolic Disorder Glucose, insulin hormones, enzymes, metabolites, etc. (i.e., control) Point of metabolic“no return” Delayed Complications Retinal, renal neural, CV, cutaneous, etc. Eg: Macro- albuminuria; Proliferative retinopathy III Modulating Factors Hypertension, diet, smoking, etc. Mechanisms Unified Theory of Brownlee Oxidative stress AGE, PKC, Hexosamine,Aldose Reductase V Late

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