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 6

Cost of PreventionTotal cost $174.3 million Diet and exercise prevented diabetes in 162

peopleMetformin prevented diabetes in 77 people

(237 people did not develop diabetes over 3 yrs)

NNT = 7 for life style intervention

NNT= 14 for MetforminCosts 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)

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Pioglitazone 1.5%per year

6.8%per year

HR = 0.19(95%, CI) = 0.09, 0.39P<0.00001

DeFronzo RA. ADA Scientific Sessions, Late-Breaking Clinical Studies, June 9, 2008.

NNT = 3.5 patients with IGT for 1 year to prevent the development of 1 case of T2DM

80% reduction in progression to DM

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

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.

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(pm

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)

Weight Loss at 1 Year (%)

0

50

100

150

*

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Before 0–2.4 2.5–6.9 157.0–14.0

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

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60

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Loss 2.25 kg

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+37%

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Plasma Lipids Improve With Weight Loss Meta-analysis of 70 Clinical Trials

Dattilo et al. Am J Clin Nutr 1992;56:320.

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*P0.05.LDL-C=low density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; TG=triglycerides.

Relationship Between Change in Weight and Blood Pressure: Trials of Hypertension Prevention II

Stevens et al. Ann Intern Med 2001;134:1.Cha

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Quintile of Weight Change

DiastolicSystolic

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)

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Reduction in Body Weight (%)Reduction in Body Weight (%)

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R2 = 0.468p = 0.001

7%

Relation Between %Weight Loss and Endothelial Function

Hamdy et al Diabetes Care 2003;26:2119-25Hamdy et al Diabetes Care 2003;26:2119-25

p<0.05 NS NS p<0.001 p<0.01 NS

IL-6 TNF- hCRP PAI-1 Leptin

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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 Benefits of weight reduction on cytokines in type 2 DM and in pre-cytokines in type 2 DM and in pre-diabetesdiabetes

Weight Loss Can Increase Life Expectancy in Obese Patients With Type 2 Diabetes

Weight Loss in First 12 Months (kg)

Lif

e E

xpec

tanc

y (y

)

18

16

14

12

10

8

00 2 4 6 8 10 12 14 16

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

Study Microvascular Macrovascular Mortality

UGDP ↔ ↔ ↔UKPDS ↓ ↓ ↔ ↓ ↔ ↓

DCCT/EDIC* ↓ ↓ ↔ ↓ ↔ ↔ACCORD ↓ ↔ ↑(unadj.), ↔ (adj.)

ADVANCE ↓ ↔ ↔VADT ↔ ↔ ↔

Initial Trial Long Term Follow-up

Meinert CL. Diabetes. 1970;19(suppl):789-830.

Goldner MG. JAMA. 1971;218(9):1400-1410.UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865. Holman RR. N Engl J Med. 2008;359(15):1577-1589.DCCT Research Group. N Engl J Med. 1993;329;977-986.Nathan DM, et al. N Engl J Med. 2005;353:2643-2653.

Gerstein HC, et al. N Engl J Med. 2008;358:2545-2559.Patel A, et al. N Engl J Med. 2008;358:2560-2572.Duckworth W, et al. N Engl J Med. 2009;360.

*T1DM study.

↑↑- - likely due to likely due to hypoglycemia hypoglycemia and weight gainand weight gain