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

Diabetes Care. 2015 Apr;38(4):620-7. doi: 10.2337/dc14-1641. Epub 2015 Jan 12.


Objective: 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.

Research design and methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Arizona / epidemiology
  • Arsenic / metabolism*
  • Arsenic / toxicity*
  • Arsenic / urine
  • Biomarkers / metabolism
  • Biomarkers / urine
  • Cohort Studies
  • 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*
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Indians, North American / statistics & numerical data*
  • Male
  • Middle Aged
  • North Dakota / epidemiology
  • Oklahoma / epidemiology
  • Prospective Studies
  • South Dakota / epidemiology


  • Biomarkers
  • Hypoglycemic Agents
  • Arsenic