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



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.



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.



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.
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD mgraupe1@jhu.edu anavasa1@jhu.edu.|Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY.
Maria
M
Grau-Pérez
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.|Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan.
Chin-Chi
CC
Kuo
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Miranda
M
Spratlen
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.
Kristina A
KA
Thayer
Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC.
Michelle A
MA
Mendez
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.
Richard F
RF
Hamman
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.
Dana
D
Dabelea
Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Denver, Aurora, CO.
John L
JL
Adgate
Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
William C
WC
Knowler
Wake Forest School of Medicine, Winston-Salem, NC.
Ronny A
RA
Bell
National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD.
Frederick W
FW
Miller
Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC.
Angela D
AD
Liese
Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC.
Chongben
C
Zhang
Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC.
Christelle
C
Douillet
Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC.|Department of Biological Sciences, North Carolina State University, Raleigh, NC.
Zuzana
Z
Drobná
Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC.|Deparment of Medicine, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC.
Elizabeth J
EJ
Mayer-Davis
Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC.
Miroslav
M
Styblo
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD mgraupe1@jhu.edu anavasa1@jhu.edu.|Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD.
Ana
A
Navas-Acien
D000293:Adolescent; D001151:Arsenic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D008297:Male; D014805:Vitamin B 12 / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D005492:Folic Acid; D001151:Arsenic; D014805:Vitamin B 12