1. Emerging Links Between Diabetes and Environmental Exposures to Arsenic and Dioxin J. Jina Shah, MD, MPH Lynn Goldman, MD, MPH Johns Hopkins School of Public Health

2. Diabetes: Definitions “a group of heterogeneous disorders with the common elements of hyperglycemia and glucose intolerance, due to insulin deficiency, impaired effectiveness of insulin action, or both” other elements “in its fully developed form” (Fajans, 1971, cited in Welborn, 1984) –microvascular complications – accelerated atherogenesis

3. Classification Criteria in Evolution but Most Still Type II More recent classifications separate etiology from severity Increasing genetic, immunological expertise allows for more specific diagnoses However, majority are classified by clinical and blood glucose criteria 90% of diabetes in the world is classified Type II

4. Why is it important?

5. High worldwide burden of disease, high projected increase 1997: 120-147 million people, 2.1% of population –66 million in Asia –22 million in Europe –13 million in North and Latin America –8 million in Africa –1 million in Oceana 2010: 213 to 215 million people (3%) –Asia and Africa to have greatest (2 to 3X) potential to increase –Asia likely to have 61% of total

6. US Prevalence 1998 NHIS data 10.5 million diabetics 5.4 million undiagnosed 13.4 million with impaired fasting glucose Even more with impaired glucose tolerance

7. Prevalence of Diabetes Among Adults,1990 (BRFSS) 6%

8. Prevalence of Diabetes Among U.S. Adults, 1993-1994 (BRFSS) 6%

9. Prevalence of Diabetes Among US Adults, 1999 (BRFSS) 6%

10. High Cost to Individual and Society Costs estimated for US $92 billion in 1997 $11,000 per capita Direct medical and productivity costs Some costs, such as suffering of patients and families, not quantifiable though people try to incorporate quality of life into calculations

11. What do we know about causes?

12. Biological Determinants Age Genetics Obesity Family history Ethnicity –People of color: greater prevalence and severity –There is more data on African Americans and Hispanics than on Asian and Native Americans

13. Environmental Determinants Diet, physical activity (obesity) Globalization, modernization, westernization Exposures such as arsenic and dioxin Other environmental exposures

14. Gene-Environment Interactions Biologically vulnerable Diabetes Environmental factors, exposures Barker hypothesis  -cell defect

15. Environmental Exposures

16. Arsenic Ingestion - DrinkingWater Bangladesh Elevated PRs for glucosuria from PR=3 to 9 in one study. PR= 1 to 3 in another study Both with dose-response patterns Taiwan Prospective cohort study: RR 2.1, RR= 1.03 for every mg-L/year in arsenic exposure. Mortality study: non significantly elevated SMRs. Retrospective cohort study: OR 8.6 to 10 in dose response fashion.

17. Arsenic Inhalation – Occupational Swedish mortality studies –Glass workers OR nonsignificant –Copper Smelter workers OR 2 to 7, dose response pattern

18. Arsenic Conclusions Evidence of an association between arsenic and diabetes in 5 separate studies Further study is warranted, along with consideration of precautionary steps to avoid exposure

19. Dioxin Exposures-Environmental Releases Residential exposures –Seveso, Italy mortality increased, not statistically significant –Jacksonville, AK Superfund site for “high” insulin concentration, ORs=9 to 56

20. Dioxin Exposures-Veterans Veterans –Ranch Hands increased mean insulin, diabetes prevalence, glucose and insulin abnormalities Those with background levels of exposure did not have significantly increased risk –Army chemical corps sprayers, increased risk

21. Dioxin Exposures – Other Industrial Workers IARC cohort exposed to phenoxy herbicides and chlorophenols –RR 2.25 for diabetes as underlying cause of death in exposed vs. non exposed Other occupational cohorts with mixed findings, no clear dose-response pattern

22. Dioxins Conclusions “Limited but suggestive” evidence of association for dioxin (finding could be due to chance, bias, or confounding) per the IOM

23. How much of a contribution are the exposures? Unknown, but probably small relative to other known risk factors IOM, VAO, Update 2000: “These studies indicate that the increased risk, if any, from herbicide or dioxin exposure appears to be small. The known predictors of diabetes risk- family history, physical inactivity and obesity continue to greatly outweigh any suggested increase from exposure to herbicides.”

24. Recommendations Better studies regarding environmental exposures – standard case definition for diabetes –good exposure measurements – prospective study design –adequate control for confounding variables

25. How do we get better exposure and outcome measures? Better tracking of exposures Better tracking of chronic diseases for specific populations and in specific localities

26. Risk reduction of known factors Encourage policy initiatives to increase physical activity and promote a more sound diet for individuals and society Address globalization, modernization, westernization, which lead to more sedentary lifestyles and higher fat diets Take steps to reduce exposure to arsenic and dioxins

27. Acknowledgements and Contact Info On this project, I was supervised by Lynn Goldman, at Johns Hopkins Bloomberg School of Public Health and supported by Physicians for Social Responsibility. This project was not done under the Centers for Disease Control, but I am currently working at CDC. I can be contacted at zat5@cdc.gov.