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Environ Int. 2018 Dec;121(Pt 1):728-740. doi: 10.1016/j.envint.2018.09.048. Epub 2018 Oct 12.

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

Author information

1
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America; Department of Environmental Health & Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America. Electronic address: mjs2376@cumc.columbia.edu.
2
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America; Fundación Investigación Clínico de Valencia-INCLIVA, Area of Cardiometabolic and Renal Risk, Valencia, Spain; Department of Statistics and Operational Research, University of Valencia, Valencia, Spain.
3
MedStar Health Research Institute, Hyattsville, MD, United States of America; Department of Medicine, Georgetown University School of Medicine, Washington, DC, United States of America.
4
Missouri Breaks Industries Research, Inc., Eagle Butte, SD, United States of America.
5
Institute of Chemistry - Analytical Chemistry, University of Graz, Austria.
6
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America.
7
Texas Biomedical Research Institute, San Antonio, TX, United States of America.
8
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America; Department of Environmental Health & Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.

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.

KEYWORDS:

American Indians; Arsenic; Arsenic metabolism; Diabetes; Metabolic syndrome; One carbon metabolism

PMID:
30321848
PMCID:
PMC6221918
[Available on 2019-12-01]
DOI:
10.1016/j.envint.2018.09.048
[Indexed for MEDLINE]
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