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

Abstract

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart StudyAbstract Number:2921AbstractBackground: Little is known about the association between arsenic metabolism and diabetes. We investigated the associations of low-moderate arsenic exposure and arsenic metabolism with diabetes in the Strong Heart Study (SHS).Methods: Prospective study in 1,694 diabetes-free American Indian participants aged 45 to 75 years living in Arizona, Oklahoma, and North and South Dakota. The sum of urine inorganic arsenic (arsenite and arsenate), monomethylated (MMA), and dimethylated (DMA) arsenic compounds at baseline was used as the biomarker of inorganic arsenic exposure from multiple sources. The proportions of urine inorganic arsenic (arsenite and arsenate, iAs), MMA and DMA over the sum of inorganic and methylated species, expressed as iAs%, MMA%, and DMA%, was used to evaluate arsenic metabolism. Diabetes was defined as a fasting plasma glucose ?126 mg/dL, venous plasma glucose 2–h after ingestion of 75 g oral glucose load ?200 mg/dL, self-reported diabetes history, and self-reported use of insulin or oral hypoglycemic medications. Findings: The adjusted hazard ratio for an interquartile range increase in MMA% was 0.76 (95% CI 0.65-0.89) when it was substituted for DMA% and 0.69 (0.52-0.90) when it was substituted for iAs%. The adjusted hazard ratio for an interquartile range increase in DMA% was 1.54 (1.19-1.98) when substituted for MMA% and 0.85 (0.65-1.11) when substituted for iAs%. The adjustedhazard ratio for an interquartile range increase in iAs% was 1.35 (1.09-1.67) when substituted for MMA% and 1.09 (0.95-1.24) when substituted for DMA%. In dose-response analyses, increasing MMA% was related to decreased incident diabetes when substituted for both% inorganic arsenic and DMA%. No interaction between arsenic exposure and arsenic metaboism was detected. Interpretation: Arsenic metabolism patterns, in particular lower MMA% and higher DMA%, was prospectively associated with incident diabetes.