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Author Notes:

Email Address: Michael Goodman :mgoodm2@emory.edu Dr. Ellen T. Chang: echang@exponent.com

The content of this paper is the sole responsibility of the authors and does not necessarily represent the views or opinions of Dow Chemical Company or Monsanto Company or any of the employers of the authors.

As the study sponsors, Dow Chemical Company and Monsanto Company did not influence the methods or materials used by the authors in conducting their independent review and synthesis of the epidemiologic literature or the interpretation of the results, nor were they involved in the preparation or review of the manuscript.

The study sponsors did not review or provide feedback on this manuscript prior to its submission.

E.T.C. and J.S.M. are employed by Exponent, Inc., a for-profit corporation that provides engineering and scientific consulting services. H.-O.A, P.B., E.T.C., M.G., and J.S.M. have consulted with private or government organizations on the health effects of environmental and occupational exposures, including Agent Orange and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

D.F. worked on the Vietnam Experience Study at the Centers for Disease Control. K.M.V.N. does not have any direct conflict of interest.


Research Funding:

This work was financially supported by the Dow Chemical Company and Monsanto Company.


  • Agent Orange
  • Diabetes mellitus
  • Dioxin
  • Dose-Response
  • Heterogeneity
  • Meta-Analysis
  • TCDD

Dose-Response Relationship Between Serum 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Diabetes Mellitus: A Meta-Analysis


Journal Title:

American Journal of Epidemiology


Volume 181, Number 6


, Pages 374-384

Type of Work:

Article | Final Publisher PDF


We systematically evaluated studies published through May 2014 in which investigators assessed the dose-response relationship between serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the occurrence of diabetes mellitus (DM), and we investigated the extent and sources of interstudy heterogeneity. The dose-response relationship between serum TCDD and DM across studies was examined using 2 dependent variables: an exposure level–specific proportion of persons with DM and a corresponding natural log-transformed ratio measure of the association between TCDD and DM. Regression slopes for each dependent variable were obtained for each study and included in a random-effects meta-analysis. Sensitivity analyses were used to assess the influence of inclusion and exclusion decisions, and sources of heterogeneity were explored using meta-regression models and a series of subanalyses. None of the summary estimates in the main models or in the sensitivity analyses indicated a statistically significant association. We found a pronounced dichotomy: a positive dose-response in cross-sectional studies of populations with low-level TCDD exposures (serum concentrations <10 pg/g lipid) and heterogeneous, but on balance null, results for prospective studies of persons with high prediagnosis TCDD body burdens. Considering the discrepancy of results for low current versus high past TCDD levels, the available data do not indicate that increasing TCDD exposure is associated with an increased risk of DM.

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© The Author 2015.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution, public display, and publicly performance, making multiple copies, distribution of derivative works, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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