1. Prevention Of Diabetes

2. Type 2 Diabetes: Hyperglycemia Insulin Resistance Relative Impairment of Insulin Secretion Pathogenesis: Poorly Understood Genetic Factors Affecting Insulin Release and Responsiveness + Environmental Factors Such As Obesity Are Important.

3. Why Prevention Type 2 diabetes  One of the most common chronic diseases in the US and one of the fastest growing diseases in the world.  In US, lifetime risk of developing Diabetes for individuals born in the year 2000 is 33% for males 39% for females.  Diabetes has enormous human and financial costs  A leading cause of heart disease, blindness, kidney failure, and amputations  Can be hard to treat once it develops  There are ways to improve glucose tolerance

4. Prediction  Ability to predict and prevent type 2 diabetes in the general population is limited. However, we can identify hi risk groups of people such as: 1) Close relatives with diabetes. 2) Obesity and body fat distribution. 3) Age and certain ethnic groups. 4) Physical inactivity. 5) Previous gestational diabetes. 6) Elevated fasting glucose. 7) Impaired glucose tolerance.

5. Family History and Risk of NIDDM  In the U.S. Positive family history imparts 2.7 fold risk of NIDDM after adjustment of other factors (Cowie, 1993).  Based on NHANES II, risk of NIDDM among Caucasians was 1.8 fold higher with one family member, 3.8 fold higher with two or more family members compared to persons with no known family history of NIDDM.

6. Obesity

7. Fat distribution

8. Birth Weight  There is an apparent inverse relationship between birth weight and risk of type 2 diabetes.  Subjects who had low birth weights have reduced beta cell function as adults, insulin resistance, and an increased incidence of type 2 diabetes.

9. Impaired Glucose Tolerance?  Risk factor for type 2 diabetes –Increases risk of type 2 diabetes 5 - 8 fold –1- 9% per year develop type 2 diabetes  Major risk factor for heart disease  IGT may be the best time to intervene – No symptoms – May be reversible – Diabetes complications have not developed

10. Gestational Diabetes  The risk of type 2 diabetes is higher in women who have gestational diabetes.  They have defects in both insulin secretion and insulin action.  2 studies have shown a five year incidence of 47- 50 percent for type 2 diabetes in women with gestational diabetes.  The greatest increase in the risk was in the first five years.

11. Diabetes Prevention Program Clinics.......................... 27 clinics 3,819 participants

12. DPP Timeline 6/94 6/95 6/96 6/97 6/98 6/99 6/00 6/01 6/02 Planning Phase Began Recruitment Began Troglitazone stopped Recruitment ended DMB Recommend s Early Termination Volunte ers unmask ed

13. DPP Goals Primary To prevent or delay type 2 diabetes in people with impaired glucose tolerance (IGT) Secondary  Reduce heart disease and stroke  Reduce risk factors for heart disease and stroke

14. Who was eligible for the DPP?  Individuals with IGT –Fasting glucose 95-125 mg/dl –American Indians  125 mg/dl And –2 hour glucose 140-199 mg/dl  Body mass index > 24 kg/m 2 (Asians > 22 kg/m 2 )  Age > 25 years  Men and women  All ethnic groups

15. Study Interventions ScreenRandomize Standard lifestyle teaching IntensiveLifestyle (n = 1079) Metformin (n = 1073) Placebo (n = 1082) Troglitazone n= 585 Until 6/98

16. Lifestyle Intervention Intensive lifestyle goals Reduction of fat and calorie intake Physical activity at least 150 minutes/week Physical activity at least 150 minutes/week Achieve and maintain at least 7% weight loss Achieve and maintain at least 7% weight loss

17. Metformin - 850 mg tablet once a day increasing after 4 weeks to two a day two a day Troglitazone - 400 mg per day Placebo- Placebo tablets Interventions Medications

18. Average Weight Change 0 6 12 18 24 30 36 42 Months in study Lifestyle Metformin + Placebo

19. 0 1 2 3 4 0 10 20 30 40 Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Plac) Lifestyle (n=1079, p<0.001 vs. Met, p<0.001 vs. Plac ) Percent of all participants developing diabetes Years in study Cumulative incidence (%) Lifestyle Metformin Placebo

20. Development of Diabetes Placebo Life-style Metformin Percent developing 11.0% 4.8% 7.8% diabetes each year Reduction of diabetes ---- 58% 31% compared with placebo Placebo, Lifestyle and Metformin

21. Percent of participants with normal glucose tolerance or diabetes at 3 years

22. Diabetes incidence rates by BMI

23. Conclusions Intensive Lifestyle and Metformin were accepted, well tolerated, and safe Intensive Lifestyle and Metformin were accepted, well tolerated, and safe Intensive lifestyle achieved weight loss and increased activity Intensive lifestyle achieved weight loss and increased activity

24. Conclusions Intensive lifestyle intervention reduced Intensive lifestyle intervention reduced the development of diabetes by 58% the development of diabetes by 58% Metformin reduced the development of Metformin reduced the development of diabetes by 31% diabetes by 31% Troglitazone reduced the development of diabetes by 23% (used for only 10 months)Troglitazone reduced the development of diabetes by 23% (used for only 10 months)

25. Conclusions Intensive Lifestyle was more effective than metformin Intensive Lifestyle was more effective than metformin Intensive Lifestyle and Metformin were effective in both women and men and all ethnic-racial groups Intensive Lifestyle and Metformin were effective in both women and men and all ethnic-racial groups

26. Conclusions Diabetes can be delayed or prevented for at least 3 years in people at high risk, such as those in the DPP