Dose-response relationship between serum 2,3,7,8-tetrachlorodibenzo-p-dioxin and diabetes mellitus: a meta-analysis.
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.
Michael
M
Goodman
K M Venkat
KM
Narayan
Dana
D
Flanders
Ellen T
ET
Chang
Hans-Olov
HO
Adami
Paolo
P
Boffetta
Jack S
JS
Mandel
D003920:Diabetes Mellitus / Q000097:blood* / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood*; D006801:Humans; D015994:Incidence; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood*; D015995:Prevalence
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins
Agent Orange; TCDD; diabetes mellitus; dioxin; dose-response; heterogeneity; meta-analysis