1. Global burden of Diabetes: Prevalence and projections Belllagio, March 16 th 2004 Peter H. Bennett, M.B., F.R.C.P. National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, U.S.A.

2. Outline Prevalence of Diabetes Estimates of future prevalence (projections) Mortality attributable to diabetes Effect of the epidemic on rates of complications Projections for ESRD

3. Newsweek, September 4, 2000 2000 Newsweek, September 4, 2000 2000 Time, September 4, 2000

6. Global Projections for the Diabetes Epidemic: 2000-2030 (in millions) NA 19.7 33.9 72% LAC 13.3 33.0 248% EU 17.8 25.1 41% A+NZ 1.2 2.0 65% SSA 7.1 18.6 261% World 2000 = 171 million 2030 = 366 million Increase 213% China 20.8 42.3 204% Wild, S et al.: Global prevalence of diabetes: Estimates for 2000 and projections for 2030 Diabetes Care 2004 In press India 31.7 79.4 251% MEC 20.1 52.8 263%

7. Estimated Number of People with Diabetes in 2000 and 2030 (and % change) Wild, S et al.: Global prevalence of diabetes: Estimates for 2000 and projections for 2030 Diabetes Care 2004. In press +176% +26% -13%

8. Estimated Number of People with Diabetes in 2000 and 2030 (and % change) Wild, S et al.: Global prevalence of diabetes: Estimates for 2000 and projections for 2030 Diabetes Care 2004 In press +308% +247% +189%

9. Estimated Number of People with Diabetes in 2000 and 2030 Wild, S et al.: Global prevalence of diabetes: Estimates for 2000 and projections for 2030 Diabetes Care 2004 In press +242% +212% +75%

10. Are these projections realistic? Based on: 1990s estimates of diabetes prevalence Demographic projections Assume constant (current) age-sex specific prevalence of diabetes

11. Changing Prevalence of Type 2 Diabetes

12. No of persons with Physician-diagnosed Diabetes in USA by year Data from the US National Health Interview Survey: http://www.cdc.gov/diabetes/statistics/prev/national/fig1.htm

13. Diabetes in the United States 1958-1993 Prevalence (%) > 65 years 55-65 years 45-54 years < 45 years Data from the US National Health Interview Survey

14. Diabetes in the United States 1980-2000 Prevalence (%) < 45 years 65-74years 45-64years 75+years Data from the US National Health Interview Survey: http://www.cdc.gov/diabetes/statistics/prev/national/fig3.htm

17. Why were former projections inaccurate? They were based on demographic changes (which are very predictable) The epidemic of diabetes is driven by other factors (some or perhaps most of which may be reflected in occurrence of IGT and IFG)

18. Importance of IGT and IFG

19. IFG IGT 'Impaired Glucose Tolerance’ (IGT) 2h post-load Plasma Glucose of 140-199mg/dl [7.8-11.0mmol/l] and FPG <126mg/dl [<7.0mmol/l] Impaired Glucose Homeostasis 'Impaired Fasting Glucose' (IFG) FPG of 100-125mg/dl [5.6 -<7.0mmol/l]

20. Incidence of Diabetes in people with Impaired Glucose Homeostasis

21. Prevalence and Incidence of Diabetes (%) in Impaired Glucose Homeostasis Prevalence of Impaired Glucose Homeostasis 5-year Cumulative Incidence of DM Hoorn 50-75y 19.4 29.7 Mauritius 25-74y 19.3 24.5 Pima Indians 15+y 15.1 24.8 Nhanes III 40-74y 19.3 ? 25% ?

22. Projections of Numbers with Diabetes* among persons aged 40-74years in USA (Millions) * Based on diabetes incidence (5% / year) in the 20% of persons with impaired glucose homeostasis; 300,000 diabetes deaths / year; Net increase = c.700,000 cases of diabetes / year

23. Proportion of new cases of Diabetes (%) in persons with NGT and Impaired Glucose Homeostasis Proportion from persons with NGT Proportion from those with IGT or IFG Hoorn 50-75y 38% 62% Mauritius 25-74y 40% 60% Pima Indians 15+y 44% 56% Nhanes III 40-74y ? 40% ? ? 60% ?

24. Projections of Numbers with Diabetes* among persons aged 40-74years in USA (Millions) * Based on diabetes incidence (5% / year) in the 20% of persons with impaired glucose homeostasis; 40% of new cases from persons with NGT; 450,000 diabetes deaths / year Net increase = c.830,000 cases of diabetes / year

26. Mortality attributable to diabetes

27. Number of Deaths with Diabetes as Underlying Cause of Death, United States, 1980-1996. CDC, Diabetes surveillance, 1999

28. Excess Deaths attributable to Diabetes Excess mortality =No of deaths in DMs – Expected no. if not DM No of DM deaths = (RR of death in DM x No. with DM) Expected No. = Mortality rate in non DMs*No. with DM Mortality rate; RR of death in DM; No. with diabetes

31. Global Projections of Excess Deaths attributable to Diabetes (in 000’s) and percent of all deaths in year 2000 AMRA 251.1 9.75% AMRD 32.2 6.1% EUR 609.0 6.4% WPR 469.3 4.1% AFR 319.2 2.6% World In 2000 = 3.164 million (5.4% of all deaths) SEAR 1154.1 6.9% Roglic et al.: Burden of mortality attributable to diabetes: Estimates for the year 2000. In preparation EMR 125.3 7.2% AMRB 194.0 7.6%

32. Consequences of the Epidemic

33. Consequences of Epidemic Disproportionate increase in duration-related complications Increase in number with diabetes

34. Effect of Epidemic of Diabetes on Duration-related complications 16 new cases/yr. Death occurs after 30y DM; Complication incidence 50% after 15y DM After 30 years No. of new cases equals no. of deaths. 05101520253035404550 Time (years) 0 150 300 450 No. of Cases 0 10 20 30 40 50 Percent with complications Cumulative No. of DM cases % with DM>15y duration Prevalence of complications (%) among those with DM

35. Incidence of Type 2 Diabetes in Pima Indians in two time periods 1965-75 1975-85 Time Period 01020304050 Incidence per 1000 person-years Age-sex adjusted rates 60% increase

36. Age-standardized mortality from Ischemic Heart Disease in diabetic and non-diabetic Pima Indians aged 35+ years, (30 year follow-up) 1965-741975-84 Non-diabetic 1985-941965-741975-84 Diabetic 1985-94 0 1 2 3 4 5 6 Mortality /1000 person-years

37. Renal disease

38. 1965197019751980198519901994 Year 0 5 10 15 20 25 Cases Dialysis Deaths Frequency of Renal Failure among Pima Indians

39. 1965-741975-841985-94 Time Period 0 4 8 12 Cases per 1000/year Incidence of Renal Failure

40. Number of persons beginning treatment for ESRD attributable to diabetes in USA by year http://www.cdc.gov/diabetes/statistics/esrd/Fig1Detl.htm

41. DIABETES IN END-STAGE RENAL FAILURE: AUSTRALIA 1980 - 2000 Year of Entry Number of DiabeticsNumber of New Patients

42. Crude and Age-adjusted incidence of ESRD related to diabetes in the United States 1984-2001 Incidence/100,000 Diabetic persons Age-adjusted rate Data from the US Renal Data System: http://www.cdc.gov/diabetes/statistics/esrd/fig7.htm Crude rate

43. Projections for number of patients with diabetes initiating ESRD treatment in USA* 20002030 (using WHO estimate) 2030 Revised projections Number with Diabetes 18 million31 million39-48 million No with new ESDR 40,00068,00086-105,000 * Assuming current incidence rates for initiating ESRD treatment remain constant

44. Summary Based on demographic changes alone: The numbers of persons with diabetes in the world will more than double in the next 30 years In developed countries they will increase by 30- 70% (mostly in older persons) In developing countries they will increase by c. 250% (mostly in 45-64y age group) These projections do not take into account any increase that is attributable to future increases in obesity

45. Summary c.3.2 million (excess) deaths were attributable to diabetes in year 2000. In the USA this is 9% of all deaths –e.g. In USA c.200,000 excess deaths vs. 14,500 for AIDs The numbers of deaths attributable to diabetes in future years will increase especially in developing countries

46. Summary Because of the current epidemic of diabetes, reflected in increasing age specific prevalence, the proportion of the diabetic population with complications will increase. This will result in a greater relative increase in complications than in diabetes prevalence. Because serious complications e.g. ESRD, typically develop after 15-20 years duration, the incidence of ESRD due to diabetes will continue to increase for at least the next 20 years

48. Thank you

49. Age-adjusted incidence of ESRD related to diabetes in the United States 1984-2001 Incidence/100,000 Diabetic persons White female Black female Hispanic male Black male Data from the US Renal Data System: http://www.cdc.gov/diabetes/statistics/esrd/fig5.htm White male Hispanic female Amer. Indian male Amer. Indian female

50. Are there better ways to predict future trends? Incidence = No. of new cases/ period of time Mortality = No. of deaths/ period of time Prevalence=Cumul.incidence – Cumul. Mortality = Number of cases at a point in time Future no. of cases = No. of prevalent cases + no. of new cases- No. of deaths(among all cases)