Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

• Published in: Diabetes care Vol. 38; no. 4; pp. 620 - 627
• Main Authors: Kuo, Chin-Chi, Howard, Barbara V, Umans, Jason G, Gribble, Matthew O, Best, Lyle G, Francesconi, Kevin A, Goessler, Walter, Lee, Elisa, Guallar, Eliseo, Navas-Acien, Ana
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.04.2015
• Subjects: Aged; Arizona - epidemiology; Arsenic; Arsenic - metabolism; Arsenic - toxicity; Arsenic - urine; Biomarkers - metabolism; Biomarkers - urine; Cohort Studies; Correlation analysis; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - urine; Environmental Exposure - adverse effects; Environmental Exposure - statistics & numerical data; Epidemiology/Health Services Research; Female; Human exposure; Humans; Hypoglycemic Agents - therapeutic use; Incidence; Indians, North American - statistics & numerical data; Male; Metabolism; Middle Aged; North Dakota - epidemiology; Oklahoma - epidemiology; Prospective Studies; South Dakota - epidemiology
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc14-1641

Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. A total of 1,694 diabetes-free participants aged 45-75 years were recruited in 1989-1991 and followed through 1998-1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥ 126 mg/dL, 2-h glucose ≥ 200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63-0.93) and 0.82 (0.73-0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism.