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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
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
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
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
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
Prevalence of Diabetes Among Adults,1990 (BRFSS) <4% 4–6% >6%
Prevalence of Diabetes Among US Adults, 1999 (BRFSS) <4% 4–6% >6%
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
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
Environmental Determinants • Diet, physical activity (obesity) • Globalization, modernization, westernization • Exposures such as arsenic and dioxin • Other environmental exposures
Gene-Environment Interactions Biologically vulnerable Diabetes Barker hypothesis B-cell defect Environmental factors, exposures
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.
Arsenic Inhalation – Occupational • Swedish mortality studies • Glass workers OR nonsignificant • Copper Smelter workers OR 2 to 7, dose response pattern
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
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
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
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
Dioxins Conclusions • “Limited but suggestive” evidence of association for dioxin (finding could be due to chance, bias, or confounding) per the IOM
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.”
Recommendations • Better studies regarding environmental exposures • standard case definition for diabetes • good exposure measurements • prospective study design • adequate control for confounding variables
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
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
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 firstname.lastname@example.org.