1. The Obesity/Diabetes Epidemic: Adiposopathy & ‘Obesity’- The New Disease! Weight Management in Obesity and DM: Emphasis on New Medical Therapies 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 5

5. Brain Central signals Stimulate NPY AGRP galanin Orexin-A dynorphin Inhibit  -MSH CRH/UCN GLP-I CART NE 5-HT External factors Emotions Food characteristics Lifestyle behaviors Environmental cues Peripheral signalsPeripheral organs Food intake Glucose CCK, GLP-1, Apo A-IV Vagal afferents Insulin Leptin Cortisol – – + Gastrointestinal tract Adipose tissue Adrenal glands Ghrelin + Regulation of Food Intake: Potential Targets for ObesityTherapy

7. Weight Change and Health Outcomes at 3 Years After Bariatric Surgery Among Individuals With Severe Obesity JAMA. 2013;310(22):2416-2425. doi:10.1001/jama.2013.280928 Percent Weight Change TrajectoriesGrowth mixture models were used to estimate weight change trajectories for each participant and to classify participants with similar modeled trajectories into groups. Lines indicate modeled group trajectories; data markers, observed median values; bars, observed interquartile ranges.

8. . Ps: 1 year sleeve (endoscopic)= 47% DM remission Escalona, Ann Surgery 2012

9. Swedish study-DM remission- EASD 2013 2 yr -70% 10 yr- 36% 15 yr- 30% 20 yr- 18% Don’t promise cure!!- but even delay over time must translate to decrease DM complications

11. Roux-en-Y restores incretin effect Sleeve- decrease postulated duodenal ‘messenger’

12. Diabetes Mellitus

13. Obesity, Insulin Resistance, Metabolic Syndrome and the Natural History of Type 2 Diabetes IR phenotype Atherosclerosis obesity hypertension  HDL,  TG, HYPERINSULINEMIA Endothelial dysfunction PCO,ED Envir.+ Other Disease Obesity (visceral) Poor Diet Inactivity Insulin Resistance Risk of Dev. Complications ETOH BP Smoking Eye Nerve Kidney  Beta Cell Secretion Genes Blindness Amputation CRF Disability MI CVA Amp Age 0-1515-40+15-50+25-70+ Macrovascular Complications IGT – OMINOUS OCTET Type II DM 8 mechanisms of hyperglycemia Microvascular Complications DEATH pp>7.8

14. Considering the Epidemic of Metabolic Syndrome, Prediabetes,Prevention Data, Undiagnosed Diabetes- SCREENING IS CRITICAL! Risk factors and screening for diabetes: Family history: whether parents or siblings have had diabetesFamily history: whether parents or siblings have had diabetes Obesity: especially with an increase in abdominal girthObesity: especially with an increase in abdominal girth High-risk ethnic group: African Americans, Hispanics, Native Americans, Asians, and Pacific IslandersHigh-risk ethnic group: African Americans, Hispanics, Native Americans, Asians, and Pacific Islanders Age: we’re looking at all ages, if patient seems at riskAge: we’re looking at all ages, if patient seems at risk Impaired fasting glucose or impaired glucose toleranceImpaired fasting glucose or impaired glucose tolerance Hypertension: blood pressure ≥ 140/90 mm Hg in adultsHypertension: blood pressure ≥ 140/90 mm Hg in adults High density lipoproteins < 35 mg/dL or triglyceride levels ≥ 250 mg/dLHigh density lipoproteins < 35 mg/dL or triglyceride levels ≥ 250 mg/dL Gestational diabetes or given birth to an infant weighing > 9 poundsGestational diabetes or given birth to an infant weighing > 9 pounds

15. Incidence 4-10%/year