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The Obesity/Diabetes Epidemic: Perspectives, Consequences, Prevention, Treatment. Part 6. Stan Schwartz MD, FACP, FACE Private Practice, Ardmore Obesity Program Cardiometabolic Diabetes Center and Affiliate, Main Line Health System Emeritus, Clinical Associate Professor
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The Obesity/Diabetes Epidemic:Perspectives, Consequences,Prevention, Treatment Part 6 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
Cost of Prevention Total cost $174.3 million Diet and exercise prevented diabetes in 162 people Metformin prevented diabetes in 77 people (237 people did not develop diabetes over 3 yrs) NNT = 7 for life style intervention NNT= 14 for Metformin Costs per person over 3 yr excluding research cost Metformin $2542 Life style intervention $2780
ACT NOWStudy Results: Time to Occurrence of Diabetes (Kaplan-Meier analysis) 0.30 Placebo 6.8% per year HR = 0.19 (95%, CI) = 0.09, 0.39 P<0.00001 0.25 80% reduction in progression to DM 0.20 Cumulative Hazard 0.15 0.10 1.5% per year Pioglitazone 0.05 0 0 10 20 30 40 50 NNT = 3.5 patients with IGT for 1 year to prevent the development of 1 case of T2DM Months DeFronzo RA. ADA Scientific Sessions, Late-Breaking Clinical Studies, June 9, 2008.
Prevention Increased with Use of Incretin 9 m, 105 pts
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-CDC’s diabetes prevention program and other Evidence-Based Interventions- • Basics, • Next Lecture in Series
150 * 100 * Insulin (pmol/L) 50 * 0 Before 15 2.5–6.9 0–2.4 7.0–14.0 Weight Loss at 1 Year (%) 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.
Loss 2.25 kg Gain 2.25 kg 60 40 20 0 -20 -40 -60 Relationship Between Weight Change and CHD Risk Factor Sum: Framingham Offspring Study Weight Change During 16-y Follow-up * +37% * +20% Change in Risk Factor Sum (%) –40% –48% * * Women Men *P<0.002 vs baseline. Wilson et al. Arch Intern Med 1999;159:1104.
HDL-C (weight stable) HDL-C (actively losing) Total Cholesterol LDL-C TG 0.02 0.5 0.0 0.00 * * -0.5 * D mmol/L per kg of Weight Loss * -0.02 -1.0 D mg/dL per kg of Weight Loss -1.5 -0.04 -2.0 * -0.06 -2.5 Plasma Lipids Improve With Weight Loss Meta-analysis of 70 Clinical Trials *P0.05. LDL-C=low density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; TG=triglycerides. Dattilo et al. Am J Clin Nutr 1992;56:320.
6 4 2 0 -2 -4 -6 -8 Diastolic Systolic Change in Blood Pressure (mm Hg) 5 1 2 3 4 Quintile of Weight Change 10 5 0 Change in Weight (kg) -5 -10 Relationship Between Change in Weight and Blood Pressure: Trials of Hypertension Prevention II Stevens et al. Ann Intern Med 2001;134:1.
Effect of Weight Change on Apnea-Hypopnea Index (AHI) 6 4 2 Mean Change in AHI (Events/h) 0 -2 -4 +10 to +20 (n=79) -20 to <-10 (n=22) -10 to <-5 (n=39) -5 to <+5 (n=371) +5 to <+10 (n=179) Change in Body Weight (%) Peppard et al. JAMA 2000;284:3015.
Relation Between %Weight Loss and Endothelial Function 7% 20 10 Change in FMD of Brachial Artery (%) 0 -10 -10 -6 2 -14 -12 -8 -4 -2 0 R2 = 0.468 p = 0.001 Reduction in Body Weight (%) Hamdy et al Diabetes Care 2003;26:2119-25
Benefits of weight reduction on cytokines in type 2 DM and in pre-diabetes p<0.05 NS NS p<0.001p<0.01 NS % Change From Baseline IL-6 TNF-ahCRP PAI-1 Leptin Adiponectin Hamdy O et al. Diabetes Care. 2003;26:2119-2125 Monzillo LUObes Res. 2003;11(9):1048-54
18 16 14 Life Expectancy (y) 12 10 8 0 0 2 4 6 8 10 12 14 16 Weight Loss in First 12 Months (kg) Weight Loss Can Increase Life Expectancy in Obese Patients With Type 2 Diabetes Lean et al. Diabet Med 1990;7:228.
Impact of Intensive Therapy in Type 2 Diabetes Summary of Major Clinical Trials: BUT Subset Evaluations Show Reduced CV Outcomes if shorter duration of DM, without significant pre-existing complications Initial Trial Long Term Follow-up ↑- likely due to hypoglycemia and weight gain