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

Diabetes Care. 2017 Jan;40(1):46-53. doi: 10.2337/dc16-0810. Epub 2016 Nov 3.


Objective: Little 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 methods: Six 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.

Results: Median ∑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.

Conclusions: Low 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.

MeSH terms

  • Adolescent
  • Arsenic / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Environmental Exposure / analysis
  • Female
  • Folic Acid / blood*
  • Humans
  • Male
  • Vitamin B 12 / blood*
  • Young Adult


  • Biomarkers
  • Folic Acid
  • Arsenic
  • Vitamin B 12