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Emerging Links Between Diabetes and Environmental
Exposures to Arsenic and DioxinJ. Jina Shah, MD, MPH
Lynn Goldman, MD, MPH
Johns Hopkins School of Public Health
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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
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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
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Why is it important?
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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
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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
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Prevalence of Diabetes Among Adults,1990 (BRFSS)
<4% 4–6% >6%
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Prevalence of Diabetes Among U.S. Adults, 1993-1994 (BRFSS)
<4% 4–6% >6%
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Prevalence of Diabetes Among US Adults, 1999 (BRFSS)
<4% 4–6% >6%
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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
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What do we know about causes?
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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
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Environmental Determinants
• Diet, physical activity (obesity)
• Globalization, modernization, westernization
• Exposures such as arsenic and dioxin
• Other environmental exposures
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Gene-Environment Interactions
Biologically vulnerable
Diabetes
Environmental factors, exposures
Barker hypothesis-cell defect
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Environmental Exposures
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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.
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Arsenic Inhalation – Occupational
• Swedish mortality studies– Glass workers
OR nonsignificant
– Copper Smelter workersOR 2 to 7, dose response pattern
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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
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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
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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
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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
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Dioxins Conclusions
• “Limited but suggestive” evidence of association for dioxin (finding could be due to chance, bias, or confounding) per the IOM
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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.”
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Recommendations
• Better studies regarding environmental exposures– standard case definition for diabetes– good exposure measurements– prospective study design– adequate control for confounding variables
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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
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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
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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 [email protected].