Association of Low-Moderate Arsenic Exposure and Arsenic Metabolism with Incident Diabetes and Insulin Resistance in the Strong Heart Family Study.

• Type of Material: Article
• Authors: Maria Grau-Perez, Johns Hopkins Bloomberg School of Public Health; Chin-Chi Kuo, Johns Hopkins Bloomberg School of Public Health; Matthew Gribble, Emory University; Poojitha Balakrishnan, Johns Hopkins Bloomberg School of Public Health; Miranda Jones Spratlen, Johns Hopkins Bloomberg School of Public Health; Dhananjay Vaidya, Johns Hopkins School of Medicine; Kevin A. Francesconi, University of Graz; Walter Goessler, University of Graz; Eliseo Guallar, Johns Hopkins Bloomberg School of Public Health; Ellen K. Silbergeld, Johns Hopkins Bloomberg School of Public Health; Jason G. Umans, Georgetown-Howard Universities Center for Clinical and Translational Science; Lyle G. Best, Missouri Breaks Industries Research, Inc.; Elisa T. Lee, University of Oklahoma Health Sciences Center; Barbara V. Howard, Georgetown-Howard Universities Center for Clinical and Translational Science; Shelley A. Cole, Texas Biomedical Research Institute; Ana Navas-Acien, Johns Hopkins Bloomberg School of Public Health
• Language: English
• Date: 2017-12-20
• Publisher: National Institute of Environmental Health Sciences (NIEHS)
• Publication Version: Final Published Version
• Copyright Statement: EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
• Final Published Version (URL): http://dx.doi.org/10.1289/EHP2566
• Title of Journal or Parent Work: Environmental Health Perspectives
• ISSN: 0091-6765
• Volume: 125
• Issue: 12
• Start Page: 127004
• End Page: 127004
• Grant/Funding Information: This study was supported by the National Institutes of Health/National Institute of Health Sciences (grants R01ES021367, R01ES025216, P42ES010349, and P30ES009089) and the National Heart, Lung, and Blood Institute (cooperative agreements grants U01-HL41642, U01-HL41652, U01-HL41654, U01-HL65520, and U01-HL65521 and research grants R01-HL109315, R01-HL109301, R01-HL109284, R01-HL109282, R01-HL109319, and R01-HL090863).
• Research Categories: Environmental Sciences; Health Sciences, Epidemiology; Engineering, Environmental

Abstract

BACKGROUND: High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity. OBJECTIVE: We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance. METHODS: We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up. RESULTS: Median ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants. CONCLUSIONS: Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk.