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

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

Why is it important?

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 U.S. Adults, 1993-1994 (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

What do we know about causes?

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

Environmental factors, exposures

Barker hypothesis-cell defect

Environmental 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 workersOR 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 zat5@cdc.gov.