Dioxin and diabetes mellitus: An analysis of the combined NIOSH and Ranch Hand data

Objectives - To reanalyze in a similar manner the two principal studies of TCDD (tetrachlorodibenzo-p-dioxin) and diabetes in an attempt to reconcile disparate results. Methods - Data from 990 United States Air Force veterans (Ranch Hand) and 1275 referents were reanalyzed, and a NIOSH population of 267 chemical workers and 227 referents. The Ranch Hand veterans had lower concentrations of lipid adjusted serum TCDD (median 12 parts per trillion (ppt)) than the NIOSH workers (median 75 ppt) when examined in the late 1980s. An analysis was conducted of the combined data sets, adopting a uniform approach to outcome definition, data analysis, and covariate control. Results - The combined exposed groups did not differ markedly from the combined non-exposed groups for prevalence of diabetes (odds ratio (OR) 1.17, 95% confidence interval (95% CI) 0.92 to 1.48), with no evidence of heterogeneity of exposure effect between studies. Also virtually no difference was found between combined exposed and non-exposed groups in mean fasting serum glucose (difference in log serum glucose 0.002, 95% CI -0.006 to 0.010), and there was little evidence in either study of a dose-response trend for fasting serum glucose. An increasing trend was found (p=0.0001) in prevalence of diabetes with increased TCDD (at the time of examination or at time of last exposure) among the Ranch Hand population, with excess risk largely confined to the highest 8% of the exposed group (>78 ppt serum TCDD), which had an OR of 3.21 (95% CI 1.81 to 5.72) versus those with <10 ppt TCDD. However, no such positive dose-response was found in the NIOSH population. Conclusions - There was little overall evidence that the exposed workers were at higher risk than the non-exposed workers of diabetes or abnormal fasting glucose. However, the Ranch Hand subjects showed a positive dose-response for diabetes, whereas the more highly exposed NIOSH subjects did not. The reason for the difference in diabetes dose-response trends between the two studies is unknown.