,Present Therapies of Type 2 Diabetes Mellitus,Edward S. Horton, MD Professor of Medicine Harvard Medical School Director of Clinical Research Joslin Diabetes Center,ACP Annual Session MTP 057&058 San Francisco, CA April 15-16, 2005,2005. American College of Physicians. All Rights Reserved.,MTP 057,Disclosure of Relationships with Commercial Companies Edward S. Horton, MD, FACP Research Grants/Contracts:Takeda, Lilly, MannKind, Sankyo Honoraria: Merck, Pfizer, Novartis, Takeda, Novo Nordisk Consultantship: Novartis,2005. American College of Physicians. All Rights Reserved.,Main Topics for Discussion,The Diabetes Epidemic The Role of Genes vs. Environment: Obesity, Metabolic Syndrome and Lifestyle Changes The Pathogenesis/Pathophysiology of DM2 and its Complications Strategies for Prevention Drugs for Treatment: Old and New The Global Approach to Treatment of DM2 and CVD Risk Factors The Need to “Treat to Target”,2005. American College of Physicians. All Rights Reserved.,23.0 M 36.2 M 57.0%,14.2 M 26.2 M 85%,48.4 M 58.6 M 21%,43.0 M 75.8 M 79%,7.1M 15.0 M 111%,39.3 M 81.6 M 108%,M = million, AFR = Africa, NA = North America, EUR = Europe, SACA = South and Central America, EMME = Eastern Mediterranean and Middle East, SEA = South-East Asia, WP = Western Pacific Diabetes Atlas Committee. Diabetes Atlas 2nd Edition: IDF 2003.,Global Projections for the Diabetes Epidemic: 2003-2025,World 2003 = 194 M 2025 = 333 M 72%,AFR,NA,SACA,EUR,SEA,WP,19.2 M 39.4 M 105%,EMME,2003 2025,2005. American College of Physicians. All Rights Reserved.,The Dual Epidemic: Obesity and Diabetes,65% of adult Americans are overweight (BMI 25) and 21% are obese (BMI 30). 24% have the Metabolic Syndrome. There are now an estimated 18 million people with DM in the USA and even more with IGT. The lifetime risk of developing DM for people born in 2000 is 33% for men and 39% for women. For Hispanic women it is 50%. In this population CVD is the major cause of mortality.,2005. American College of Physicians. All Rights Reserved.,The Prevalence of Overweight and Diabetes over 10 Years,Mokdad et al. Diabetes Care. 2000; 23(9):1278-83. Mokdad et al. JAMA. 2000;286(10):1195-200.,Overweight BMI 25 Kg/m2,Diabetes & Gestational Diabetes,49% increase,25% increase,2005. American College of Physicians. All Rights Reserved.,CHANGES IN OUR LIFESTYLE!,WHAT IS DRIVING THE DUAL EPIDEMIC?,2005. American College of Physicians. All Rights Reserved.,To diabetes,Metabolic Syndrome ?,Diabetes,R. Heine MD,2005. American College of Physicians. All Rights Reserved.,2005. American College of Physicians. All Rights Reserved.,2005. American College of Physicians. All Rights Reserved.,2005. American College of Physicians. All Rights Reserved.,The Role of Genes vs. the Environment,2005. American College of Physicians. All Rights Reserved.,Obesity (esp. Abdominal Obesity),Genetic Variation In CVD Risk Factor Regulation,Elevated Blood Pressure,Atherogenic Dyslipidemia,Insulin Resistance,Pro- thrombotic State,Pro- inflammatory State,Physical Inactivity,Aging,Hyperglycemia,The Insulin Resistance Syndrome,Modified from S. Grundy MD,2005. American College of Physicians. All Rights Reserved.,Obesity (esp. Abdominal Obesity),Genetic Variation In CVD Risk Factor Regulation,Elevated BP BP 130/85 mmHg,Atherogenic Dyslipidemia,Insulin Resistance,Pro- thrombotic State,Pro- inflammatory State,Waist Circumference Men: 102 cm (40 in) Women: 88 cm (35 in),TG 150 mg/dL HDL-C 40 mg/dL (M) 50 mg/dL (F),Fasting Glucose 110 mg/dL *,Metabolic Syndrome ATP III (3 of 5),2005. American College of Physicians. All Rights Reserved.,National Health and Nutrition Examination Survey III, 1988-1994,Prevalence of the Metabolic Syndrome Among US Adults Using the ATP III Criteria,Age-Adjusted Prevalence is 23.7% n= 8814,Ford et al. JAMA 2002;278:356-359,2005. American College of Physicians. All Rights Reserved.,The Metabolic Syndrome in People with IGT or Diabetes,33% of people 50 yrs. and older with IGT have MS compared to 35-40% in the general population (NHANES III) (Alexander CM et al Diabetes 2003; 52:1210-1214) Only limited data on prevalence of MS in DM2 (approximately 60-65% in Type 2 DM) The increased risk of CVD in IGT and DM2 is well established, but the role of hyperglycemia vs. other CVD risk factors is not well understood. How much does MS contribute? No prospective studies of the development of MS in people with IGT or DM2,2005. American College of Physicians. All Rights Reserved.,DIABETES AND CARDIOVASCULAR DISEASE,2005. American College of Physicians. All Rights Reserved.,CHD Mortality (incidence/1,000),Eschwege E et al. Horm Metab Res. 1995;17(suppl):41-46.,G 140 mg/dL,5,4,3,2,1,0,IGT,G 200 mg/dL (newly diagnosed diabetes),Known Diabetes,P 0.001,(6055),(690),(158),(135),IGT Progressively Increases Risk of CHD Mortality: Paris Prospective Study (10-year follow-up),2005. American College of Physicians. All Rights Reserved.,DECODE: