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Original Research
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
Diabetes Care 2016 Nov; dc160810. https://doi.org/10.2337/dc16-0810
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Abstract

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 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.

Footnotes

  • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc16-0810/-/DC1.

  • Received April 13, 2016.
  • Accepted October 13, 2016.
  • © 2016 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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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
Diabetes Care Nov 2016, dc160810; DOI: 10.2337/dc16-0810

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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
Diabetes Care Nov 2016, dc160810; DOI: 10.2337/dc16-0810
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