TY - JOUR
T1 - Association of low-moderate arsenic exposure and arsenic metabolism with incident diabetes and insulin resistance in the strong heart family study
AU - Grau-Perez, Maria
AU - Kuo, Chin Chi
AU - Gribble, Matthew O.
AU - Balakrishnan, Poojitha
AU - Spratlen, Miranda Jones
AU - Vaidya, Dhananjay
AU - Francesconi, Kevin A.
AU - Goessler, Walter
AU - Guallar, Eliseo
AU - Silbergeld, Ellen K.
AU - Umans, Jason G.
AU - Best, Lyle G.
AU - Lee, Elisa T.
AU - Howard, Barbara V.
AU - Cole, Shelley A.
AU - Navas-Acien, Ana
N1 - 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).
Publisher Copyright:
© 2017, Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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 (RAs). 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 RAs, iAs%, MMA%, and DMA% was 4:4 lg=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 RAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. RAs 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. https://doi.org/10.1289/EHP2566.
AB - 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 (RAs). 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 RAs, iAs%, MMA%, and DMA% was 4:4 lg=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 RAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. RAs 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. https://doi.org/10.1289/EHP2566.
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U2 - 10.1289/EHP2566
DO - 10.1289/EHP2566
M3 - Article
C2 - 29373862
AN - SCOPUS:85045481178
SN - 0091-6765
VL - 125
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 12
M1 - 127004
ER -