Abstract
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.
Highlights
Researchers have extensively studied the US veterans of the Vietnam War who participated in Operation Ranch Hand, which involved aerial spraying of Agent Orange, a mixture of herbicides contaminated with TCDD [5,6,7,8,9,10]
In 1999, in response to a request from the Department of Veterans Affairs, the Institute of Medicine convened a committee to review the evidence regarding the possible association of TCDD and other chemical compounds found in the herbicides used in Vietnam with diabetes mellitus (DM)
War veterans with low-level exposures who had not participated in Operation Ranch Hand [38,39,40], 1 assessed women exposed to TCDD in a residential setting after an industrial accident in Seveso, Italy [24], and 1 was based on a sample of persons in the general Japanese population [25]
Summary
Researchers have extensively studied the US veterans of the Vietnam War who participated in Operation Ranch Hand, which involved aerial spraying of Agent Orange, a mixture of herbicides contaminated with TCDD [5,6,7,8,9,10] These veterans formed the core of the Air Force Health Study (AFHS), which began in 1982 and involved extensive periodic physical examinations of the Operation Ranch Hand cohort and the comparison subcohorts over a 20-year follow-up period [11]. In 1999, in response to a request from the Department of Veterans Affairs, the Institute of Medicine convened a committee to review the evidence regarding the possible association of TCDD and other chemical compounds found in the herbicides used in Vietnam with DM.
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