Edward Gregg, PhD Epidemiology and Statistics Branch Division of Diabetes Translation

1. Modifiable Risk Factors for Type 2 Diabetes2009 Middle Eastern RegionEpidemiology SupercourseAlexandria, Egypt Edward Gregg, PhD Epidemiology and Statistics Branch Division of Diabetes Translation Centers for Disease Control and Prevention Atlanta, GA

2. Key Steps in the Public Health Research Leading to Public Health Decision Making • Surveillance and Descriptive Epidemiology • Monitor health of the population • Identify public health problems and their magnitude • Evaluate levels of care • Identify high risk populations amenable to intervention • Analytic and Clinical Epidemiology: • Identify modifiable risk factors • Examine effectiveness of interventions in the clinical setting aimed at the individual • Health Services Research, Cost-Effectiveness, Translation Research • Examine the effectiveness of different health service, program, or policy-level interventions. • Examine the cost effectiveness of successful interventions

3. Range of Potential Priorities in the Public Health Response to Diabetes Normal IGT Type 2 DM Disability Death Complications Primary Secondary Tertiary prevention prevention prevention • Control of complications and management of disability. • Prevention of diabetes complications • Assure access to care • Prevention of diabetes among persons of high risk. • Prevention and management of risk factors in the whole population.

4. Common Study Designs Used in Epidemiologic Research • Observational Studies • Cross-sectional • Retrospective (case control) • Prospective (cohort studies) • Ecologic Studies • Intervention Studies • Quasi-experimental studies • Controlled intervention studies • Clinical • Health Service • Community • Cost-effectiveness studies cross-sectional Retrospective cohort Intervention Yes No

5. Risk factors: Characteristic of an individual or his/her environment that increases the chance of a health-related condition. • Major Types: • Causal vs non-causal • Modifiable vs non modifiable • Behavioral • Physiologic • Environmental • Contextual

6. How do we use risk factors? • To contribute to understanding of etiology of disease. • To guide the development of effective interventions.

7. Bradford Hill Criteria for Evaluation of the Evidence of Causality • Strength of Association • Dose-response effect • Temporality • Consistency of evidence • Biological plausibility • Specificity of association • Experimentation

8. How do we use risk factors? • To contribute to understanding of etiology of disease. • To guide the development of effective interventions. • To assist in efficient identification of people who will benefit from intervention.

9. Step 1: Clinical Observations/Impressions “There are entirely too many diabetic patients in the country. Statistics for the last thirty years show so great an increase in the number that, unless this were in part explained by a better recognition of the disease, the outlook for the future would be startling.” ”The physician should take pride in the prevention of diabetes in his practice. Obese patients should be frankly told that they are candidates for diabetes”. ”But it is to the diabetic patient and his relatives that one can look most confidently for help in preventing diabetes. They should be encouraged to disseminate information about its prevention”. Joslin EP. The Prevention of Diabetes Mellitus JAMA 1921; 76 (2):79-84.

10. Kahn et al., Nature, 2006

11. Evidence from observational epidemiology:Ecologic Studies

12. Migration Studies: Association Between Westernization and Diabetes Prevalence in Susceptible Populations New Guinea Nauru Chinese Indian Australian Aborigines King, Diabetes Care, 1993; 1998; Diamond J, Nature, 2003

13. Schulz et al., Diabetes Care, 2006

14. Natural Experiments Franco et al., Am J Epidemiol, 2007

15. Clues from Descriptive Epidemiology

17. Diabetes Prevalence among U.S. Adults Aged 20 - 74 8.83% 5.03% Age and sex adjusted Gregg et al., Prev Med, 2007

18. Trends in the proportion of total intake devoted to macronuetriends (left x-axis) and mean total Energy Intake (right x-axis) among U.S. adults age 20-74, 1971 to 2000 Total Intake (kcals) MMWR, 2004

19. Percentage of total carbohydrates obtained from whole grains (smaller circles) and corn syrup (larger circles) in the United States Gross et al., Am J Clin Nutr, 2004

20. Trends in % of Meals Eaten at Home and Trends in Total Kcal Intake in Meals and Snacks in the U.S., 1977-1996. Nielsen and Popkin, JAMA, 2003

22. Portion Sizes for Selected Key Foot Items for Americans Aged 2 and Older, 1977-1996. Nielsen and Popkin, JAMA, 2003

23. Healthy Trends Lower % of saturated fat Lower % of total fat in diet Higher % of carbohydrates More fruits and vegetables Unhealthy Trends Increased portion sizes Decreased quality of carbs Increased total intake More meals out of the home Increased soda intake Reduced breakfast frquency Summary of Secular Trends in U.S. Dietary Behavior

24. Luckovich, Atlanta Journal Constitution

25. Trends in Leisure-Time Physical Inactivity by Age, Sex, and Race/Ethnicity - United States, 1994-2004 Centers for Disease Control and Prevention, MMWR, 2005

26. Evidence from Cohort Studies and Analytic Epidemiology

27. Body Mass Index and 1-year Risk of Diabetes (Ford ES et al. AJE 1997;146:214-22) %- Point Absolute Increase 0 0.031 0.204 0.315 0.329 0.675 0.850 1.256 1.668 2.237 Increase per 100,000 0 31 204 315 329 675 850 1,256 1,668 2,237 Cumulative Increase BMI <22 22-<23 23-<24 24-<25 25-<27 27-<29 29-<31 31-<33 33-<35 35+ 1-y Risk (%) 0. 224 0. 255 0. 428 0. 539 0. 553 0. 899 1.074 1.480 1.892 2.461 RR 1 1.18 2.44 2.97 3.04 5.07 5.70 8.21 10.89 14.64 0 550 1,554 7,565

28. Relative risk of incident diabetes per standard deviation of BMI and Waist circumference from a meta-analysis of 32 studies Vasquez, Epidemiol Rev, 2007

29. Hu et al., Arch Intern Med, 2001

30. Potential Impact of Physical Activity on Diseases and Conditions: Across the Life Span Adolescent - Young Adult - Adult - Mid-aged - Older Adult - 10 20 30 40 50 60 70 80 90 Lifestyle forming, habituation, and maintenance Obesity Diabetes CVD Physical Function Falls Fracture Stroke Cancers Quality of life / Mental health

31. Dietary factors as independent diabetes risk factors • Characteristics of fat intake • Whole grain / cereal fibers • Dairy • Glycemic load • “Western diet” • Fast food intake • Soda intake • Alcohol intake • Coffee consumption

32. Diabetes OR per 1kg Birth weight=0.78

33. Gestational Diabetes and the Incidence of Type 2 Diabetes: A systematic review (Kim et al., Diabetes Care, 2002)

34. Systematic Review of the Incidence of Diabetes Associated with Various Categories of Glycemia *extremely variable; 1-7% in European pops; 23-34% in Asian pops. Gerstein et al., Diab Res Clin Pract, 2007

35. Non-Traditional Risk Factors

38. Lee et al., Diab Care, 2007

39. Upstream / Contextual Factors as Risk Factors for Obesity and Diabetes • Poverty • Education • Food insecurity • Food environment • Neighborhood factors

40. County-level Estimates of Diagnosed Diabetes for Adults aged ≥ 20 years: United States 2005

42. Age ↑ Family History ↑ Gestational Diabetes ↑ Obesity / fat distribution ↑ Physical Activity / fitness ↓ Smoking ↑ Very low birth weight ↑ Depression ↑ Antipsychotic medications ↑ Anti-Retrovial therapy ↑ Dietary Factors Carbohydratess ↓ Fats ↑↓ Glycemic load ↑ Cereal fiber / whole grain ↓ Dairy products ↓ High fructose corn syrup ↑ Sugar-sweetened bevarages ↑ Alcohol ↓ Coffee ↓ Summary: Risk Factors for Type 2 Diabetes

43. Major Type 2 Diabetes Risk Factors Under New (or Renewed) Investigation • Genetic markers • Insulin resistance biomarkers (inflammation markers, adipocytokines, hepatocytokines) • Sleep; sleep apnea • Depression; vital exhaustion • Vitamin D deficiency • Anti-retroviral treatment • New antipsychotic treatment • Fatty liver disease • Hepatitis

44. Proportion of Participants Developing Diabetes During the Finnish and U.S. Diabetes Prevention Studies Finland United States Control Control Metformin Lifestyle Lifestyle Tuomilehto, N Engl J Med, 2001; DPP Research Group, N Engl J Med, 2002

45. Characteristics of Controlled Trials of Lifestyle-based Interventions on Diabetes Incidence Pan et al., 1997; Tuomilehto et al., 2001, Knowler et al., 2002

46. Application of Risk Scores to Public Health Intervention Application of Risk Scores to Public Health Intervention

47. Applications of Risk Scores to Diabetes Prevention in Finland And Germany Schwarz, Horm Metab Res, 2008

48. Discussion Questions • Are the modifiable risk factors in your country and region likely to be different from these? • For the average individual? • As predictors of trends over time? • If yes, what would those risk factors be? • What major types of research are needed in your country to examine new and emerging risk factors? • What are the major candidate interventions for publication in your country and region?