1. The Obesity/Diabetes Epidemic: Perspectives, Consequences, Prevention, Treatment Stan Schwartz MD, FACP, FACE Private Practice, Ardmore Obesity Program Cardiometabolic Diabetes Center and Affiliate, Main Line Health System Emeritus, Clinical Associate Professor University of Pennsylvania Part 4

2. Obesity-Associated Illnesses That Occur in Childhood Idiopathic intracranial hypertension Pulmonary disorders –Obstructive sleep apnea –Hypoventilation syndrome Hypertension Hypercholesterolemia Proteinuria Nonalcoholic fatty liver disease Gallbladder disease Type 2 diabetes mellitus Polycystic ovarian syndrome Orthopedic –Blount ’ s disease –Slipped capital femoral epiphysis Skin –Acanthosis nigricans –Striae

3. Overweight Overweight and Obesity Increase the Risk of CV Disease Mortality Data are from 1 million men and women (average age, 57 years) followed for 16 years who never smoked and had no history of disease at enrollment. Calle EE, et al. N Engl J Med. 1999;341:1097-1105. Normal weightObese Relative Risk of Cardiovascular Disease Mortality 0.6 3.0 2.6 2.2 1.8 1.4 1.0 >18 25 30 >40 BMI, kg/m 2 Women Men

4. Obesity and Metabolic Syndrome: A Cluster of Coronary Heart Disease Risk Factors Adapted from Grundy SM. J Clin Endocrinol Metab. 2005;89:2595-2600. Raised Blood Pressure Autonomic Dysfunction Proinflammatory State Obesity Insulin Resistance Genetic Susceptibility Diet Physical Inactivity Stress Prothrombotic State  Small Low-Density Lipoprotein Particles  High-Density Lipoprotein Cholesterol  Triglycerides Atherogenic Dyslipidemia Slide Source: Obesityonline.org

6. Additional Risk Factors Each additional risk factor increases chronic disease risk hypertension (>140/90) impaired glucose tolerance (110 – 125 mg/dl) hypertriglyceridemia (>150mg/dl) hypercholesterolemia (>240mg/dl, >160mg/dl LDL) low HDL-C (<35mg/dl) family history (parent/sibling) of early CHD, hpt, DM –M>55, F>65 Age M>45 or F>55

7. Risk Factor Sum* and 16-Year Coronary Heart Disease Risk: Framingham Offspring Study *Low HDL-C, high cholesterol, high BMI, high systolic BP, high triglyceride, high glucose. Wilson et al. Arch Intern Med 1999;159:1104. MenWomen Relative Risk of CHD Risk factors (n) 0 1 2 33 0 1 2 3 4 5 6

8. Obesity, IRS, Type 2 Diabetes and Atherosclerotic Disease Obesity carries with it increase CV Risk Factors Risk factors for macrovascular disease accrue before the diagnosis of diabetes as > 50% of patients with newly diagnosed Type 2 diabetes have pre- existing cardiovascular disease. 2-4 fold > risk of ASVD in diabetic vs. normal patients Cardiovascular disease causes 80% of all diabetic mortality- 75% coronary, 25% cerebral vascular l Type 2 diabetes is associated with an increased risk of morbidity and mortality from cerebrovascular disease versus the general population, and > HgA1c, >risk

9. Folsom et al. Arch Intern Med 2000;160:2117. Body Mass Index Tertile 32 3 1 1 2 Relative Risk Waist-Hip Ratio Tertile Abdominal Fat Distribution Increases the Risk of Coronary Heart Disease The Iowa Women ’ s Health Study

10. Elevated Visceral Fat Metabolically more active Greater effect on visceral organs –Greater Insulin Resistance hyperinsulinemia impaired glucose tolerance Type 2 diabetes –Hyperlipidemia Hypertriglyceridemia Hypercholesterolemia –Hypertension

11. Visceral Fat Distribution: Normal vs Type 2 Diabetes Normal Type 2 Diabetes 2-11