Citation: Environment International. 121(Pt 1):728-740, 2018 Oct 12..Journal: Environment international.Published: ; 2018ISSN: 0160-4120.Full author list: Spratlen MJ; Grau-Perez M; Umans JG; Yracheta J; Best LG; Francesconi K; Goessler W; Balakrishnan P; Cole SA; Gamble MV; Howard BV; Navas-Acien A.UI/PMID: 30321848.Subject(s): Adolescent | Adult | Aged | Aged, 80 and over | *Arsenic/ae [Adverse Effects] | *Arsenicals/ae [Adverse Effects] | Biomarkers | *Carbon/me [Metabolism] | Diabetes Mellitus/ci [Chemically Induced] | *Diabetes Mellitus/ep [Epidemiology] | *Environmental Exposure | Female | Humans | Incidence | Indians, North American | Male | Middle Aged | Prospective Studies | United States/ep [Epidemiology] | Young AdultInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1016/j.envint.2018.09.048 (Click here)Abbreviated citation: Environ Int. 121(Pt 1):728-740, 2018 Oct 12.Abstract: BACKGROUND: Inorganic 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.Abstract: METHODS: We 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.Abstract: RESULTS: Of the 935 participants free of both diabetes and metabolic syndrome at baseline, 279 (29.8%) developed metabolic syndrome over a median of 5.3years 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 B<sub>6</sub> 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% (beta=2.57, 95% CI: 0.22, 4.92) and lower HOMA2-IR (GMR=0.79, 95% CI=0.66, 0.93 per 5years 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.Abstract: CONCLUSIONS: Our 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.Abstract: Copyright (c) 2018. Published by Elsevier Ltd.