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

MedStar author(s):
Citation: Environmental Health Perspectives. 125(12):127004, 2017 12 20PMID: 29373862Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Arsenic/ur [Urine] | *Cacodylic Acid/ur [Urine] | *Diabetes Mellitus, Type 2/ep [Epidemiology] | *Environmental Exposure | *Environmental Pollutants/ur [Urine] | *Insulin Resistance | Adult | Female | Humans | Incidence | Indians, North American | Male | Middle Aged | Prospective Studies | United States/ep [Epidemiology] | Young AdultYear: 2017Local holdings: Available online from MWHC library: 1972 - presentISSN:
  • 0091-6765
Name of journal: Environmental health perspectivesAbstract: 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.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. https://doi.org/10.1289/EHP2566.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 (SIGMAAs). 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.OBJECTIVE: We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance.RESULTS: Median SIGMAAs, iAs%, MMA%, and DMA% was 4.4 mug/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 SIGMAAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. SIGMAAs 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.All authors: Balakrishnan P, Best LG, Cole SA, Francesconi KA, Goessler W, Grau-Perez M, Gribble MO, Guallar E, Howard BV, Jones Spratlen M, Kuo CC, Lee ET, Navas-Acien A, Silbergeld EK, Umans JG, Vaidya DFiscal year: FY2018Digital Object Identifier: Date added to catalog: 2018-02-20
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 29373862 Available 29373862

Available online from MWHC library: 1972 - present

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.

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. https://doi.org/10.1289/EHP2566.

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 (SIGMAAs). 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.

OBJECTIVE: We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance.

RESULTS: Median SIGMAAs, iAs%, MMA%, and DMA% was 4.4 mug/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 SIGMAAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. SIGMAAs 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.

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