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

Author:

Grau-Pérez Maria12,Kuo Chin-Chi134,Spratlen Miranda1,Thayer Kristina A.5,Mendez Michelle A.6,Hamman Richard F.7,Dabelea Dana7,Adgate John L.8,Knowler William C.9,Bell Ronny A.10,Miller Frederick W.11,Liese Angela D.12,Zhang Chongben6,Douillet Christelle6,Drobná Zuzana613,Mayer-Davis Elizabeth J.614,Styblo Miroslav6,Navas-Acien Ana115

Affiliation:

1. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

2. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY

3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

4. Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan

5. Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC

6. Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC

7. Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO

8. Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Denver, Aurora, CO

9. Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ

10. Wake Forest School of Medicine, Winston-Salem, NC

11. National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD

12. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC

13. Department of Biological Sciences, North Carolina State University, Raleigh, NC

14. Deparment of Medicine, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC

15. Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD

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 (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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Environmental Health Sciences

Publisher

American Diabetes Association

Subject

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

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