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

ABSTRACT: 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 (?As). 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 ?As, iAs%, MMA%, and DMA% was 4.4 ?g/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 ?As was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ?As 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.

SUBMITTER: Grau-Perez M

PROVIDER: S-EPMC5963590 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Grau-Perez Maria M Kuo Chin-Chi CC Gribble Matthew O MO Balakrishnan Poojitha P Jones Spratlen Miranda M Vaidya Dhananjay D Francesconi Kevin A KA Goessler Walter W Guallar Eliseo E Silbergeld Ellen K EK Umans Jason G JG Best Lyle G LG Lee Elisa T ET Howard Barbara V BV Cole Shelley A SA Navas-Acien Ana A

Environmental health perspectives 20171220 12

<h4>Background</h4>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.<h4>Objective</h4>We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance.<h4>Methods</h4>We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic expo ...[more]

PMID: 29373862

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Project description:BackgroundInorganic arsenic exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. A more efficient arsenic metabolism profile (lower MMA%, higher DMA%) has been associated with reduced risk for arsenic-related health outcomes; however, this profile has also been associated with increased risk for diabetes-related outcomes. The mechanism behind these contrasting associations is equivocal; we hypothesized one carbon metabolism (OCM) may play a role.MethodsWe evaluated the association between OCM-related variables (nutrient intake and genetic variants) and both arsenic metabolism biomarkers (iAs%, MMA% and DMA%) and diabetes-related outcomes (metabolic syndrome, diabetes, HOMA2-IR and waist circumference) in 935 participants free of prevalent diabetes and metabolic syndrome from the Strong Heart Family Study, a family-based prospective cohort comprised of American Indian tribal members aged 14+ years.ResultsOf the 935 participants free of both diabetes and metabolic syndrome at baseline, 279 (29.8%) developed metabolic syndrome over a median of 5.3 years of follow-up and of the 1458 participants free of diabetes at baseline, 167 (11.3%) developed diabetes over follow-up. OCM nutrients were not associated with arsenic metabolism, however, higher vitamin B6 was associated with diabetes-related outcomes (higher HOMA2-IR and increased risk for diabetes and metabolic syndrome). A polymorphism in an OCM-related gene, methionine synthase (MTR), was associated with both higher MMA% (β = 2.57, 95% CI: 0.22, 4.92) and lower HOMA2-IR (GMR = 0.79, 95% CI = 0.66, 0.93 per 5 years of follow-up). Adjustment for OCM variables did not affect previously reported associations between arsenic metabolism and diabetes-related outcomes; however, the association between the MTR variant and diabetes-related outcomes were attenuated after adjustment for arsenic metabolism.ConclusionsOur findings suggest MMA% may be a partial mediator in the association between OCM and diabetes-related outcomes. Additional mediation analyses with longer follow-up period are needed to confirm this finding. Further research is needed to determine whether excess B vitamin intake is associated with increased risk for diabetes-related outcomes.

Project description:BackgroundArsenic has been associated with hypertension, though it is unclear whether associations persist at the exposure concentrations (e.g. <100 μg/L) in drinking water occurring in parts of the Western United States.MethodsWe assessed associations between arsenic biomarkers and systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension in the Strong Heart Family Study, a family-based cohort of American Indians from the Northern plains, Southern plains, and Southwest. We included 1910 participants from three study centers with complete baseline visit data (2001-2003) in the cross-sectional analysis of all three outcomes, and 1453 participants in the prospective analysis of incident hypertension (follow-up 2006-2009). We used generalized estimating equations with exchangeable correlation structure conditional on family membership to estimate the association of arsenic exposure biomarker levels with SBP or DBP (linear regressions) or hypertension prevalence and incidence (Poisson regressions), adjusting for urine creatinine, urine arsenobetaine, and measured confounders.ResultsWe observed cross-sectional associations for a two-fold increase in inorganic and methylated urine arsenic species of 0.64 (95% CI: 0.07, 1.35) mm Hg for SBP, 0.49 (95% CI: 0.03, 1.02) mm Hg for DBP, and a prevalence ratio of 1.10 (95% CI: 1.01, 1.21) for hypertension in fully adjusted models. During follow-up, 14% of subjects developed hypertension. We observed non-monotonic relationships between quartiles of arsenic and incident hypertension. Effect estimates were null for incident hypertension with continuous exposure metrics. Stratification by study site revealed elevated associations in Arizona, the site with the highest arsenic levels, while results for Oklahoma and North and South Dakota were largely null. Blood pressure changes with increasing arsenic concentrations were larger for those with diabetes at baseline.ConclusionsOur results suggest a modest cross-sectional association of arsenic exposure biomarkers with blood pressure, and possible non-linear effects on incident hypertension.

Dataset Information

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

Publications

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

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