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 2

2. Health Benefits of Modest Weight Loss (5-10%)  Decreased cardiovascular risk  Decreased blood glucose and insulin levels  Decreased blood pressure  Decreased LDL and triglycerides, increased HDL  Decrease in severity of sleep apnea  Reduced symptoms of degenerative joint disease  Improvement in gynecologic conditions  Multiple cardiovascular risk factors and other complications can be improved. Source: The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults..

3. Insulin Sensitivity Improves With Weight Loss in Patients With Type 2 Diabetes *P<0.01 vs before. Wing et al. Arch Intern Med 1987;147:1749. Insulin (pmol/L) Weight Loss at 1 Year (%) 0 50 100 150 * * * Before 0–2.4 2.5–6.9  15 7.0–14.0

4. Plasma Lipids Improve With Weight Loss Meta-analysis of 70 Clinical Trials Dattilo et al. Am J Clin Nutr 1992;56:320. -0.06 -0.04 -0.02 0.00 0.02 Total Cholesterol LDL-CTG HDL-C (weight stable) HDL-C (actively losing)  mmol/L per kg of Weight Loss -2.5 -2.0 -1.5 -0.5 0.0 0.5  mg/dL per kg of Weight Loss * * * * * *P  0.05. LDL-C=low density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; TG=triglycerides.

5. Relationship Between Change in Weight and Blood Pressure: Trials of Hypertension Prevention II Stevens et al. Ann Intern Med 2001;134:1. Change in Weight (kg) Change in Blood Pressure (mm Hg) 1234 5 -10 -5 0 5 10 6 4 2 0 -2 -4 -6 -8 Quintile of Weight Change Diastolic Systolic

6. Effect of Weight Change on Apnea-Hypopnea Index (AHI) Peppard et al. JAMA 2000;284:3015. Change in Body Weight (%) -20 to <-10 (n=22) -10 to <-5 (n=39) -5 to <+5 (n=371) +5 to <+10 (n=179) +10 to +20 (n=79) 6 4 2 0 -2 -4 Mean Change in AHI (Events/h)

7. 2 0 -2-4 -6 -8 -10 -12-14 20 10 0 -10 Reduction in Body Weight (%) Reduction in Body Weight (%) Change in FMD of Brachial Artery (%) R 2 = 0.468 p = 0.001 7% Relation Between %Weight Loss and Endothelial Function Hamdy et al Diabetes Care 2003;26:2119-25

8. p<0.05 NS NS p<0.001 p<0.01 NS IL-6 TNF-  hCRP PAI-1 Leptin % Change From Baseline Monzillo LU Obes Res. 2003;11(9):1048-54 Hamdy O et al. Diabetes Care. 2003;26:2119-2125 Adiponectin Benefits of weight reduction on cytokines in type 2 DM and in pre-diabetes

10. Relationship Between Weight Change and CHD Risk Factor Sum: Framingham Offspring Study *P<0.002 vs baseline. Wilson et al. Arch Intern Med 1999;159:1104. Weight Change During 16-y Follow-up Men Women 0 20 40 60 -20 -40 -60 Change in Risk Factor Sum (%) * * * * Loss  2.25 kg Gain  2.25 kg +37% –40% –48% +20%

11. Weight Loss Can Increase Life Expectancy in Obese Patients With Type 2 Diabetes Weight Loss in First 12 Months (kg) Life Expectancy (y) 18 16 14 12 10 8 0 02468 121416 Lean et al. Diabet Med 1990;7:228.

12. Outline Epidemiology and Economics of obesity/diabetes Perspectives on Obesity Consequences of Obesity, Prediabetes, Obesity Obesity/ Diabetes Risk Factors, Obesity/ Diabetes Onset can be Prevented or Delayed – Early Risk Identification and Intervention. Medical Benefits to Weight Loss Treatment- –Basics, Generalities –Obesity Lifestyle- Diet, Activity, Behavior Medications –Weight Control, WEIGHT REDUCTION in DIABETES

13. Weight Loss Goals in Lifestyle Modification “ The initial goal of weight loss therapy for overweight patients is a reduction in body weight of about 10 percent….Moderate weight loss of this magnitude can significantly decrease the severity of obesity-associated risk factors. ” Most patients desire much greater weight losses. Higher goals may be related to more weight loss. NIH/NHLBI, NAASO. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, MD: NIH, 2000.