1 / 54

Prevention of Type 2 Diabetes Mellitus

Prevention of Type 2 Diabetes Mellitus. Key Questions and A Call to Action. Prevention of Type 2 Diabetes Mellitus: Table of Contents. Section 1. Why is prevention of type 2 diabetes imperative?. Projecting the Future Diabetes Population: The Imperative for Change.

Download Presentation

Prevention of Type 2 Diabetes Mellitus

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Prevention of Type 2 Diabetes Mellitus Key Questions and A Call to Action

  2. Prevention of Type 2 Diabetes Mellitus: Table of Contents

  3. Section 1 Why is prevention of type 2 diabetes imperative?

  4. Projecting the Future Diabetes Population: The Imperative for Change U.S. Population withDiabetes (%) Boyle JP, et al. Popul Health Metr. 2010;8(29):1-12.

  5. Percentage of U.S. Adults Who Were Obese or Had Diagnosed Diabetes 2008 1994 2000 2008 1994 2000 No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Obesity (BMI ≥30 kg/m2) Diabetes No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% ≥9.0% Centers for Disease Control and Prevention: National Diabetes Surveillance System. Available online at: http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Accessed 10/3/2011.

  6. Section 2 whaT IS THE EVIDENCE THAT TYPE 2 DIABETESCAN BE PREVENTED OR DELAYED?

  7. Lifestyle InterventionsCan Prevent Type 2 Diabetes Onset • Several randomized trials have shown interventions (lifestyle, medications) can decrease rate of onset of diabetes • Lifestyle: Da Qing, Finnish Diabetes Prevention Study, Diabetes Prevention Program • Medications: Diabetes Prevention Program (metformin), The Stop-NIDDM (acarbose), DREAM (rosiglitazone), ACT-NOW (pioglitazone)

  8. Lifestyle InterventionsDa Qing Study Methods • 110,660 adults from 33 Da Qing, China, health care clinics screened in 1986 for IGT, type 2 diabetes mellitus • 577 adults with IGT (WHO criteria) randomized to control (n=138) or one of three lifestyle interventions (n=438) • Diet only • Exercise only • Diet + exercise • Follow-up at 2-year intervals over 6 years to identify those who developed diabetes Pan XR, et al. Diabetes Care. 1997;20:537-544.

  9. Lifestyle InterventionsDa Qing Study Results • Cumulative incidence of diabetes at6 years was significantly decreased in the active intervention groups (P<0.05) • When analyzed by clinic, each active intervention group differed significantly from the control (P<0.05) Pan XR, et al. Diabetes Care. 1997;20:537-544.

  10. Lifestyle InterventionsDa Qing Study Results • When stratified as lean or overweight(BMI < or ≥25 kg/m2), relative decrease in rate of development of diabetes in lifestyle intervention groups was similar • After adjusting for differences in baseline BMI and fasting glucose, all interventions were associated with diabetes risk reduction Pan XR, et al. Diabetes Care. 1997;20:537-544.

  11. Lifestyle InterventionsDa Qing Study Conclusions • Active intervention with diet and/or exercise led to a significant decrease in incidence of diabetes over a 6-year period (1986-1992) among those with IGT • Diabetes incidence (per 100 person years) per year • Control: 14.1 (95% CI 11.2-17.0) • Lifestyle intervention: 7.9 (95% CI, 6.8-9.1) Pan XR, et al. Diabetes Care. 1997;20:537-544.

  12. Lifestyle InterventionsFinnish Diabetes Prevention Study • 522 subjects, 40-65 years of age • BMI ≥25 kg/m2;IGT: 2-h PPG 140-200 mg/dL • Control group: general oral and written information diet and exercise • Intervention group: individualized • Reduce weight ≥5% • Decrease fat ≤30%, saturated fat ≤10% energy • Increase fiber to at least 15 g/1000 kcal • Moderate exercise ≥30 minutes/day • Primary end point: diagnosis of diabetes Tuomilehto J, et al for the Finnish Diabetes Prevention Study Group.N Engl J Med. 2001;344:1343-1350.

  13. Lifestyle InterventionsFinnish Diabetes Prevention Study • 172 men, 350 women; mean age 55 y • Mean BMI 31 kg/m2 • Mean duration of follow-up 3.2 years *P<0.001 Tuomilehto J, et al for the Finnish Diabetes Prevention Study Group.N Engl J Med. 2001;344:1343-1350.

  14. Lifestyle InterventionsFinnish Diabetes Prevention Study • Reduction in incidence of type 2 diabetes was directly associated with changes in lifestyles of high-risk subjects (ie, those with IGT) • Modifiable risk factors such as obesity, physical inactivity, suggested as main nongenetic determinants of diabetes • These results demonstrate that 22 subjects with IGT must be treated with lifestyle intervention for 1 year (or 5 subjects for 5 years) to prevent 1 case of diabetes Tuomilehto J, et al for the Finnish Diabetes Prevention Study Group.N Engl J Med. 2001;344:1343-1350.

  15. Lifestyle InterventionsDiabetes Prevention Program • 3,234 nondiabetic persons in 27 clinical centers • BMI ≥24 kg/m2 (≥22 kg/m2 in Asians) • IGT: FPG 95-125 mg/dL or 2-h PPG 140-199 mg/dL • From 1996-1999, randomly assigned to • Standard lifestyle + placebo (n=1082) • Standard lifestyle + metformin, initiated at 850 mg orally once daily; at 1 month, increased to 850 mg twice daily (n=1073) • Intensive lifestyle intervention (n=1079) Knowler WC, et al. for the Diabetes Prevention Program Research Group.N Engl J Med. 2002;346:393-403.

  16. Lifestyle InterventionsDiabetes Prevention Program Goals of intensive lifestyle intervention • 7% loss of body weight • Dietary fat goal: 25% of calories from fat • Calorie intake goal: 1200-1800 kcal/day based on initial body weight • >150 minutes of physical activities weekly • Similar in intensity to brisk walking; at least 700 kcal/week • Group received 16-lesson curriculum Knowler WC, et al. for the Diabetes Prevention Program Research Group.N Engl J Med. 2002;346:393-403.

  17. Lifestyle InterventionsDiabetes Prevention Program • Mean age 50.6 years • 67.7% women; 45.3% members of minority groups • Mean BMI 34.0 kg/m2 • 69.4% had a family history of diabetes • Average follow-up: 2.8 years(range, 1.8-4.6) Knowler WC, et al. for the Diabetes Prevention Program Research Group.N Engl J Med. 2002;346:393-403.

  18. Lifestyle InterventionsDiabetes Prevention Program • Those assigned to lifestyle intervention had greater weight loss and increase in physical activity than participants receiving metformin or placebo • Lifestyle intervention more effective in restoring normal post-load glucose values Results: average weight loss (P<0.001) Knowler WC, et al. for the Diabetes Prevention Program Research Group.N Engl J Med. 2002;346:393-403.

  19. Lifestyle InterventionsDiabetes Prevention Program Results: intensive lifestyle intervention Knowler WC, et al. for the Diabetes Prevention Program Research Group.N Engl J Med. 2002;346:393-403.

  20. MedicationsDPP: Metformin Intervention • Metformin, intensive lifestyle modification delayed or prevented type 2 diabetes vs placebo (11%/year incidence) • Placebo: 11%/year incidence • Metformin: 7.8%/year incidence* • Lifestyle intervention: 4.8%/year incidence* • Risk reduction: • 31% by metformin • 58% by lifestyle • 39% lifestyle vs metformin *P<0.001 vs placebo Knowler WC, et al. for the Diabetes Prevention Program Research Group.N Engl J Med. 2002;346:393-403.

  21. MedicationsDPP: Metformin Intervention • Intensive lifestyle intervention more effective than either metformin or placebo • By subgroup, metformin more effective if: • FPG >110 mg/dL • Age <60 years • BMI >35 kg/m2 • Gender, ethnicity, 2-h PGG, NOT predictive of response • Use metformin in high-risk individuals Knowler WC, et al. for the Diabetes Prevention Program Research Group.N Engl J Med. 2002;346:393-403.

  22. MedicationsThe STOP-NIDDM: Acarbose • Acarbose reduced risk of new • Hypertension >140/90; 5.3% absolute risk reduction (P=0.006) • Myocardial infarction (P=0.02) • Any CVD event: CHD, CV death or stroke, CHF, PVD (P=0.03) Acarbose100 mg TIDn=682 Placebon=686 25% Relative Risk Reduction P=0.0022 Reprinted with permission from Chiasson JL, et al. Lancet. 2002;359(9323): 2072-2077;Chiasson JL, et al. JAMA. 2003;290(4):486-494.

  23. MedicationsDREAM: Rosiglitazone 60%Relative Risk Reduction HR 0.40 (0.35–0.46) P<0.0001 Reprinted with permission from DREAM Trial Investigators. Lancet. 2006;368(9541):1096-1105.

  24. MedicationsACT NOW: Pioglitazone • Pioglitazone reduced risk of type 2 diabetes mellitus by 72% vs placebo (HR 0.28; 95% CI 0.16–0.49 P<0.001) • Conversion to normal glucose tolerance: 48% of patients with pioglitazone vs 28% with placebo (P<0.001) • Pioglitazone reduced fasting glucose,2-hour glucose, HbA1c • Weight gain, edema observed in the pioglitazone arm DeFronzo RA, et al, for the ACT NOW Study. N Engl J Med. 2011;364:1104-1115.

  25. Section 3 DO PREVENTION INTERVENTIONS HAVE SUSTAINED EFFECTS?

  26. Lifestyle InterventionsDa Qing Study 20-Year Follow-Up • Combined lifestyle intervention vs control • 51% lower incidence of diabetes during active intervention • 43% lower incidence over 20 years • 3.6 years fewer with diabetes Li G, et al. Lancet. 2008;371:1783-1789.

  27. Lifestyle InterventionsDa Qing Study 20-Year Follow-Up • No significant difference in rate of • First CVD event (HR 0.98; 95% CI, 0-71-1.37) • CVD mortality (HR 0.83; 0.48-1.40) • All-cause mortality (HR 0.96; 0.65-1.41) • Study had limited statistical power to detect differences in these outcomes • Lifestyle interventions over 6 years can prevent, delay diabetes for up to 14 years after active intervention • Unclear whether lifestyle interventions also lead to reduced CVD, mortality Li G, et al. Lancet. 2008;371:1783-1789.

  28. Lifestyle InterventionsFinnish DPS 7-Year Follow-Up 43% Relative Risk Reduction Reprinted with permission from Lindström J, et al. Lancet. 2006;368(9548):1673-1679.

  29. DPP: Metformin Had Sustained EffectAfter Drug Washout • Brief (1-2 week) drug washout study at end of Diabetes Prevention Program trial • After washout, diabetes was more frequently diagnosed in metformin vs. placebo (1.49; 0.93, 2.38; P=0.098) • DPP primary analysis: metformin decreased diabetes risk by 31% • Washout: 26% accounted for by pharmacological effect of metformin • Postwashout: diabetes reduced by 25% Diabetes Prevention Program Research Group. Diabetes Care. 2003;26:977-980.

  30. Rosiglitazone Had No Sustained EffectAfter Drug Washout: DREAM • During rosiglitazone vs placebo washout • Primary outcome, new-onset diabetes or death: 10.5% vs 9.8% (P=0.59) • Secondary outcome, regression to normoglycemia: 21.5% vs 23.8% (P=0.33) • Median follow-up: 71 days (range, 63-86 days) • Rosiglitazone substantially reduced incidence of type 2 diabetes (DREAM); however, when withdrawn, this effect is not sustained The DREAM Trial Investigators. Diabetes Care. 2011;34:1265-1269.

  31. Lifestyle InterventionsSummary • Lifestyle intervention continues to have an effect; most drugs do not Lifestyle Pharmacologic Diabetes Care. 1997;20:537-544; N Engl J Med. 2002;344:1343-1350;N Engl J Med. 2002;346;393-403; Diabetes Care. 2011;34:1265-1269;Lancet. 2002;359(9323): 2072-2077 N Engl J Med. 2011;364:1104-1115.

  32. Section 4 Are we preventing type 2 diabetes or delaying it?

  33. Diabetes Prevention Program10-Year Follow-Up Study • During 10-year follow-up since randomization • Original lifestyle group lost, then partly regained weight • Modest weight loss with metformin maintained • Diabetes incidence per 100 person-years *vs placebo Diabetes Prevention Program. Lancet. 2009;374:1677-1686.

  34. Section 5 Is diabetes prevention cost-effective?

  35. Cost-Effectiveness of Lifestyle Modification or Metformin: DPP • Active interventions (vs placebo) would: QALY = Quality Adjusted Life Years Herman WH, et al for the Diabetes Prevention Program Research Group.Ann Intern Med. 2005:142:323-332.

  36. Diabetes Prevention Program 10-Year Cost-Effectiveness • 10-year within-trial cost-effectiveness of the interventions • Intensive lifestyle • Metformin • Data on resource utilization, cost, and quality of life collected prospectively • Economic analyses performed from health system and societal perspectives Diabetes Prevention Program Research Group. Diabetes Care. 2012;35:723-730.

  37. Diabetes Prevention Program 10-Year Cost-Effectiveness • Lifestyle cost-effective, metformin marginally cost-saving vs placebo • Investment in lifestyle, metformin interventions for diabetes prevention in high-risk adults provides good value Incremental cost-effectiveness ratios from three different perspectives; ∆cost/∆QALY *Includes direct medical costs and direct nonmedical costs including participant time †Both costs and QALYs are discounted at 3% Diabetes Prevention Program Research Group. Diabetes Care. 2012;35:723-730.

  38. Section 6 Can evidence-based interventions be delivered effectively in lower-cost settings?

  39. DEPLOY Pilot Study: Diabetes Prevention in the Community • Adults BMI ≥24 kg/m2, ≥2 diabetes risk factors, blood glucose 110-199 mg/dL • Randomized to group-based DPP lifestyle intervention or brief counseling (control) Ackermann RT, et al. Am J Prevent Med. 2008;35:357-363.

  40. Practice-Based Opportunities for Weight Reduction (POWER) • Obese patients achieve, sustain significant weight loss with behavioral interventions *P<0.001 vs control arm Appel LJ, et al. N Engl J Med. 2011;365:1959-68.

  41. Diabetes TeleHealth Improves Diabetes Self-Management • 1-year remote DSME intervention, Diabetes TeleCare (dietitian, nurse/certified diabetes educator • Improved metabolic control, reduced CV risk *P=0.003 vs. baseline †P=0.004 vs. baseline Davis RM, et al. Diabetes Care. 2010;33:1712–1717.

  42. Section 7 Will diabetes prevention “bend the curve” of the epidemic?

  43. CDC Modeling Study to ReduceFuture Diabetes Prevalence • Five-state model • Potential effect of hypothetical preventive intervention delivered to all with IFG • If 50% participated and incidence reduced by 50%, would equal 25% reduction in annual incidence of diabetes in the population with IFG • Would lower the increase in prevalence by 2050 to 1 in 4 (vs 1 in 3) Boyle JP, et al. Popul Health Metr. 2010;8(29):1-12.

  44. Section 8 How can we most effectively prevent or delay type 2 diabetes?

  45. Most People with Diabetes Are Unaware of Their Condition • Data analyzed from 1,402 adults without diabetes • 2005–2006 NHANES participants • Valid fasting plasma glucose, oral glucose tolerance tests • Almost 30% of the US adult population had prediabetes in 2005–2006; only 7.3% were aware they had it • Adoption of risk reduction behaviors suboptimal Geiss LS, et al. Am J Prevent Med. 2010;38:403-409.

  46. We Need to Test People at Risk *For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range. ADA. I. Classification and Diagnosis. Diabetes Care 2012;35(suppl 1):S13. Table 3.

  47. Recommendations: Testing for Diabetes in Asymptomatic Patients • Consider testing overweight/obese adults with one or more additional risk factors • In those without risk factors, begin testing at age 45 years (B) • If tests are normal • Repeat testing at least at 3-year intervals (E) • Use A1C, FPG, or 2-h 75-g OGTT (B) • In those with increased risk for future diabetes • Identify and, if appropriate, treat other CVD risk factors (B) ADA. II. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S13.

  48. Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (1) 1. Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2*) and have additional risk factors: • HDL cholesterol level<35 mg/dl (0.90 mmol/l) and/or a triglyceride level >250 mg/dl (2.82 mmol/l) • Women with polycystic ovarian syndrome (PCOS) • A1C ≥5.7%, IGT, or IFG on previous testing • Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) • History of CVD *At-risk BMI may be lower in some ethnic groups. ADA. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S14. Table 4.

  49. Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (2) ADA. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S14. Table 4.

  50. DPP: Managing Prediabetes • For those found to have prediabetes, provide support or referral to encourage • Weight loss of at least 7% • Moderate exercise of at least 150 minutes per week • Consider metformin for certain patients • Obese (BMI ≥35 kg/m2) • <60 years (most effective, 25-44 years) • Lifestyle interventions feasible, morecost-effective than medications American Diabetes Association, 2012.

More Related