The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study

Abstract

OBJECTIVELittle is known about arsenic and diabetes in youth. We examined the association of arsenic with type 1 and type 2 diabetes in the SEARCH for Diabetes in Youth Case-Control (SEARCH-CC) study. Because one-carbon metabolism can influence arsenic metabolism, we also evaluated the potential interaction of folate and vitamin B12 with arsenic metabolism on the odds of diabetes.RESEARCH DESIGN AND METHODSSix hundred eighty-eight participants <22 years of age (429 with type 1 diabetes, 85 with type 2 diabetes, and 174 control participants) were evaluated. Arsenic species (inorganic arsenic [iAs], monomethylated arsenic [MMA], dimethylated arsenic [DMA]), and one-carbon metabolism biomarkers (folate and vitamin B12) were measured in plasma. We used the sum of iAs, MMA, and DMA (∑As) and the individual species as biomarkers of arsenic concentrations and the relative proportions of the species over their sum (iAs%, MMA%, DMA%) as biomarkers of arsenic metabolism.RESULTSMedian ∑As, iAs%, MMA%, and DMA% were 83.1 ng/L, 63.4%, 10.3%, and 25.2%, respectively. ∑As was not associated with either type of diabetes. The fully adjusted odds ratios (95% CI), rescaled to compare a difference in levels corresponding to the interquartile range of iAs%, MMA%, and DMA%, were 0.68 (0.50–0.91), 1.33 (1.02–1.74), and 1.28 (1.01–1.63), respectively, for type 1 diabetes and 0.82 (0.48–1.39), 1.09 (0.65–1.82), and 1.17 (0.77–1.77), respectively, for type 2 diabetes. In interaction analysis, the odds ratio of type 1 diabetes by MMA% was 1.80 (1.25–2.58) and 0.98 (0.70–1.38) for participants with plasma folate levels above and below the median (P for interaction = 0.02), respectively.CONCLUSIONSLow iAs% versus high MMA% and DMA% was associated with a higher odds of type 1 diabetes, with a potential interaction by folate levels. These data support further research on the role of arsenic metabolism in type 1 diabetes, including the interplay with one-carbon metabolism biomarkers.

Type 2 Diabetes in Youth: New Lessons from the SEARCH Study

“…In a case-control sub-study, plasma levels of arsenic were evaluated in relation to both type 1 and type 2 diabetes. While associations were observed for type 1 diabetes, no association was observed for type 2 diabetes [15]. One challenge in estimating the effect of arsenic on disease development is estimating exposure, and chronic sources of exposure may be more relevant than recent, high levels of exposure.…”

Developmental Exposure to Endocrine Disrupting Chemicals and Type 1 Diabetes Mellitus

“…For example, prenatal exposure to arsenic is associated with populations of cord blood immune cells linked to the development of autoimmunity, and with epigenetic changes in newborns, some involved in pathways relevant for T1DM and T2DM ( 19 – 22 ). We do not yet know if these immunological changes found at birth are persistent or will have later-life health effects, but numerous epidemiological studies have linked chronic arsenic exposure to the development of T2DM, and arsenic metabolism is associated with T1DM ( 23 ).…”

Endocrine Disrupting Chemicals and Type 1 Diabetes

“…Lower levels of inorganic arsenic and higher levels of arsenic metabolites were associated with both higher odds and prevalence of T1D. Stronger associations were found in subjects who also had higher folate levels [92].…”