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Prevention of Diabetes Mellitus

Prevention of Diabetes Mellitus. Prof. Adel El-Etriby Professor of Cardiology Ain Shams Faculty of Medicine. Rationale for Prevention. The incidence of type 2 of diabetes is increasing in epidemic proportions throughout the world. Once type 2 diabetes develops, it is difficult to treat.

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Prevention of Diabetes Mellitus

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  1. Prevention ofDiabetes Mellitus Prof. Adel El-EtribyProfessor of CardiologyAin Shams Faculty of Medicine

  2. Rationale for Prevention • The incidence of type 2 of diabetes is increasing in epidemic proportions throughout the world. • Once type 2 diabetes develops, it is difficult to treat. • Prevention of type 2 diabetes would result in a significant reduction in social and economic costs.

  3. 30 to 64 Years of Age 14 Men 12 Women 10 8 % of Population 6 4 2 0 European Pacific American Prevalence of IGT in Different Ethnic Populations African & Asian Data from World Health Organization. Available at http://www.who.int/ncd/dia/databases3.htm. Accessed April 26, 2003.

  4. 80 1995 2000 2025 70 60 50 Estimated Prevalence (millions) 40 30 20 10 0 Africa Americas Eastern Mediterranean Europe Southeast Asia Western Pacific Current and Projected Prevalence Rates for Diabetes World Health Organization. World Health Report 1997: Message from the Director-General. Available at www.who.int/whr/1997/message.pdf. Accessed November 8, 2002.

  5. Gestational diabetes, polycystic ovarian syndrome, and parity Genetic factors • Ethnicity • Family history Type 2 Diabetes Diet Increasing age Physical inactivity Central obesity Risk Factors for Type 2 Diabetes

  6. -23% -25% -38% -46% Risk of type 2 diabetes associated with level of physical activity Relative Risk U.S. Nurses Health Study Adjusted for age, smoking. hypertension, family history, menopause, high cholesterol 8 year follow-up Quartile of physical activity vs Q1 Hu et al., JAMA 282:1433, 1999

  7. Stages in the natural history of Type 2 diabetes Disability Death Normal IGT NIDDM Complications Genetic predisposition Preclinical state Clinical disease Disability Death Complications Primary Secondary Tertiary prevention prevention prevention

  8. Recent Prospective Diabetes Prevention Trials • Finnish Diabetes Prevention Study (DPS) • Chinese Prevention Trial • US Diabetes Prevention Program (DPP) • Study to Prevent Non–Insulin-Dependent Diabetes Mellitus (STOP-NIDDM trial), Europe • Troglitazone in Prevention of Diabetes Study (TRIPOD), United States • Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study, Sweden

  9. 1.0 0.9 Intervention 0.8 Cumulative Probability of No Diabetes 0.7 Control 58% reduction in relative risk 0.6 0.5 0 1 2 3 4 5 6 Years Finnish DPS: Intensive Lifestyle Intervention Reduces Diabetes Risk Adapted from Tuomilehto J et al. N Engl J Med. 2001;344:1343-1349.

  10. 43% reduction in relative risk (RR) with diet + exercise • 88% reduction in RR with acarbose • 77% reduction in RR with metformin P = .09 P = .0002 P = .0001 Chinese Prevention Trial: Lifestyle Intervention, Acarbose, and Metformin Reduce Risk of Diabetes Data from Yang W et al. Chin J Endocrinol Metab. 2001;17:131-136.

  11. Lifestyle advice: 58% decrease in diabetes incidence Metformin: 31% decrease in diabetes incidence 40 30 P <.001 Cumulative Incidence of Diabetes at 3 y (%) 20 P <.001 10 0 Placebo Metformin Lifestyle DPP: Metformin/Lifestyle Advice Reduces Diabetes Risk Data from DPP Research Group. N Engl J Med. 2002;346:393-403.

  12. 25% reduction in RR 1.00 0.90 Acarbose 0.80 Placebo Cumulative Probability of No Diabetes 0.70 0.60 P = .0022 0.50 0.40 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 Days After Randomization STOP-NIDDM: Acarbose Reduces Diabetes Risk Adapted from Chiasson J-L et al. Lancet. 2002;359:2072-2077.

  13. 25 20 15 • 55% reduction in RR • (30 mo on drug) Annual Incidence of Diabetes (%) 10 P <.01 5 0 Placebo Troglitazone TRIPOD: Troglitazone Reduces Diabetes Risk Data from Buchanan TA et al. Diabetes. 2002;51:2796-2803.

  14. 37% reduction in RR 10 8 P = .0032 6 Cumulative Incidence of Type 2 Diabetes (%) 4 2 0 Placebo Orlistat XENDOS: Orlistat Reduces Diabetes Risk Sjöström L et al. Poster presented at: Ninth International Congress on Obesity. São Paulo, Brazil. August 24-29, 2002.

  15. New-Onset Diabetes in Trials Using Inhibitors of the RAAS • HOPE: Heart Outcomes Prevention Evaluation Study • CAPPP: Captopril Prevention Project • SOLVD: Studies of Left Ventricular Dysfunction • LIFE: Losartan Intervention for Endpoint Reduction Study

  16. Placebo Ramipril 10 P <.001 5 P <.001 0 New Diagnosis of Diabetes HOPE Study: ACE Inhibitor Ramipril Reduces Risk of Cardiovascular Disease and Diabetes in High-Risk Patients 33% risk reduction Data from HOPE Study Investigators. N Engl J Med. 2000;342:145-153.

  17. Conventional Captopril 13% risk reduction 20 10 15 P <.04 Patients (%) 10 5 P = NS 5 0 0 Primary End Point: Composite of Incidence of Diabetes Fatal and Nonfatal MI, Stroke, Death from CV Causes CAPPP Study: Results Data from Hansson L et al. Lancet. 1999;353:611-616.

  18. N = 291 • 16.5% absolute risk reduction in development of diabetes No. of New Diabetes Cases P <.0001 SOLVD: Enalapril Reduces New-Onset Diabetes Risk in CHF Patients Vermes E et al. Circulation. 2003;107:1291-1296.

  19. Atenolol 30 Losartan P <.05 25 • 25% reduction in RR 20 Events/1000 Patient-Years P <.001 15 10 5 0 Primary Endpoint: CV Death, MI, New-Onset Diabetes and Stroke LIFE Study: Results Dahlöf B et al. Lancet. 2002;359:995-1003.

  20. P .001 P = .04 15 11.6% 9.8% 8.1% 10 % 5 0 Chlorthalidone Amlodipine Lisinopril ALLHAT: Incidence of New-Onset Diabetes at 4 Years* *43.2% lower onset of new diabetes with lisinopril compared to chlorthalidone (P .001 at 4 y). ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997.

  21. Summary • Type 2 diabetes and CVD are common chronic diseases that cause suffering to millions and are a major drain on healthcare resources • Disease prevention is possible and desirable • Patients with IGT at high risk of diabetes and CVD are ideal population for type 2 diabetes prevention trials • Intensive lifestyle interventions may not be broadly applicable or sustained; effective pharmacological therapies must also be identified • Several drug classes have been shown to reduce incidence of type 2 diabetes

  22. Summary • It seems that the combination of an insulin sensitizer and a RAAS is the best tool for prevention and future studies will clarify this fact.

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