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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Targeted metabolomics to understand the association between arsenic metabolism and diabetes-related outcomes: Preliminary evidence from the Strong Heart Family Study.

Authors: Spratlen, Miranda J; Grau-Perez, Maria; Umans, Jason G; Yracheta, Joseph; Best, Lyle G; Francesconi, Kevin; Goessler, Walter; Bottiglieri, Teodoro; Gamble, Mary V; Cole, Shelley A; Zhao, Jinying; Navas-Acien, Ana

Published In Environ Res, (2019 01)

Abstract: BACKGROUND: Inorganic arsenic exposure is ubiquitous and both 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. This profile, however, has also been associated with increased risk for diabetes-related outcomes. OBJECTIVES: The mechanism behind these conflicting associations is unclear; we hypothesized the one-carbon metabolism (OCM) pathway may play a role. METHODS: We evaluated the influence of OCM on the relationship between arsenic metabolism and diabetes-related outcomes (HOMA2-IR, waist circumference, fasting plasma glucose) using metabolomic data from an OCM-specific and P180 metabolite panel measured in plasma, arsenic metabolism measured in urine, and HOMA2-IR and FPG measured in fasting plasma. Samples were drawn from baseline visits (2001-2003) in 59 participants from the Strong Heart Family Study, a family-based cohort study of American Indians aged ≥14 years from Arizona, Oklahoma, and North/South Dakota. RESULTS: In unadjusted analyses, a 5% increase in DMA% was associated with higher HOMA2-IR (geometric mean ratio (GMR)= 1.13 (95% CI: 1.03, 1.25)) and waist circumference (mean difference=3.66 (0.95, 6.38). MMA% was significantly associated with lower HOMA2-IR and waist circumference. After adjustment for OCM-related metabolites (SAM, SAH, cysteine, glutamate, lysophosphatidylcholine 18.2, and three phosphatidlycholines), associations were attenuated and no longer significant. CONCLUSIONS: These preliminary results indicate that the association of lower MMA% and higher DMA% with diabetes-related outcomes may be influenced by OCM status, either through confounding, reverse causality, or mediation.

PubMed ID: 30316100 Exiting the NIEHS site

MeSH Terms: Adult; Arizona; Arsenic*/metabolism; Arsenic*/toxicity; Cohort Studies; Diabetes Mellitus*/epidemiology; Diabetes Mellitus*/metabolism; Environmental Exposure; Female; Humans; Indians, North American; Male; Metabolomics; Middle Aged; Oklahoma

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