Arsenic, one carbon metabolism and diabetes-related outcomes in the Strong Heart Family Study. (December 2018)

• Record Type: Journal Article
• Authors: Spratlen, Miranda J.; Grau-Perez, Maria; Umans, Jason G.; Yracheta, Joseph; Best, Lyle G.; Francesconi, Kevin; Goessler, Walter; Balakrishnan, Poojitha; Cole, Shelley A.; Gamble, Mary V.; Howard, Barbara V.; Navas-Acien, Ana
• Is Part Of: Environment international. Volume 121(2018)Part 1
• Page Start: 728
• Page End: 740
• Publication Date: 2018-12
• Subjects: ∑As Arsenic exposure measured as urine arsenic levels -- CBS Cystathionine β-synthase -- DMA Dimethylarsinic acid -- eGFR Estimated glomerular filtration rate -- FFQ Food frequency questionnaire -- HOMA2-IR Homeostasis model assessment for insulin resistance -- iAs Inorganic arsenic -- MTR Methionine synthase -- MTRR Methionine synthase reductase -- MTHFD1 Methylenetetrahydrofolate dehydrogenase -- MTHFR Methylenetetrahydrofolate reductase -- MMA Monomethylarsonic acid -- OCM One carbon metabolism -- PEMT Phosphatidylethanolamine N-methyltransferase -- SAM S-adenosylmethionine -- SAH S-adenosylhomocysteine -- SHMT1 Serine hydroxymethyltransferase 1 -- SNP Single nucleotide polymorphism -- SHS Strong Heart Study -- SHFS Strong Heart Family Study; Arsenic -- Arsenic metabolism -- Metabolic syndrome -- Diabetes -- One carbon metabolism -- American Indians; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2018.09.048
• Languages: English
• ISSNs: 0160-4120

Abstract

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. 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. Results: Of the 935 participants free of both diabetes and metabolic syndrome at baseline, 279 (29.8%) developed metabolic syndrome over a median of 5.3 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. 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. Highlights: One carbon metabolism was assessed as B vitamin intake and genetic polymorphisms. Higher vitamin B6 intake was associated with increased risk for diabetes outcomes. A methionine synthase polymorphism was associated with arsenic metabolism. The same polymorphism was also associated with insulin resistance. Arsenic metabolism, one carbon metabolism and diabetes appear to be interconnected.