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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)146-157
Number of pages12
JournalEnvironmental research
Volume168
DOIs
StatePublished - Jan 2019

Keywords

  • American Indians
  • Metabolomics
  • arsenic metabolism
  • diabetes
  • one carbon metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Science(all)

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    Spratlen, M. J., Grau-Perez, M., Umans, J. G., Yracheta, J., Best, L. G., Francesconi, K., Goessler, W., Bottiglieri, T., Gamble, M. V., Cole, S. A., Zhao, J., & Navas-Acien, A. (2019). Targeted metabolomics to understand the association between arsenic metabolism and diabetes-related outcomes: Preliminary evidence from the Strong Heart Family Study. Environmental research, 168, 146-157. https://doi.org/10.1016/j.envres.2018.09.034