The association of arsenic exposure and metabolism with type 1 and type 2 diabetes in youth: The search case-control study

Maria Grau-Pérez, Chin Chi Kuo, Miranda Spratlen, Kristina A. Thayer, Michelle A. Mendez, Richard F. Hamman, Dana Dabelea, John L. Adgate, William C. Knowler, Ronny A. Bell, Frederick W. Miller, Angela D. Liese, Chongben Zhang, Christelle Douillet, Zuzana Drobná, Elizabeth J. Mayer-Davis, Miroslav Styblo, Ana Navas-Acien

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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 sumof iAs,MMA, andDMA (∑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 arsenicmetabolismin type 1 diabetes, including the interplay with one-carbon metabolism biomarkers.

Original languageEnglish (US)
Pages (from-to)46-53
Number of pages8
JournalDiabetes care
Issue number1
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing


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