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.

LanguageEnglish (US)
Pages146-157
Number of pages12
JournalEnvironmental research
Volume168
DOIs
StatePublished - Jan 1 2019

Fingerprint

Metabolomics
diabetes
Arsenic
Medical problems
Metabolism
arsenic
metabolism
Carbon
Waist Circumference
Dynamic mechanical analysis
carbon
fasting
Metabolites
Plasmas
plasma
Fasting
metabolite
family
Lysophosphatidylcholines
North American Indians

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Science(all)

Cite this

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

In: Environmental research, Vol. 168, 01.01.2019, p. 146-157.

Research output: Contribution to journalArticle

Spratlen, MJ, Grau-Perez, M, Umans, JG, Yracheta, J, Best, LG, Francesconi, K, Goessler, W, Bottiglieri, T, Gamble, MV, Cole, SA, 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, vol. 168, pp. 146-157. https://doi.org/10.1016/j.envres.2018.09.034
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. / Targeted metabolomics to understand the association between arsenic metabolism and diabetes-related outcomes : Preliminary evidence from the Strong Heart Family Study. In: Environmental research. 2019 ; Vol. 168. pp. 146-157.
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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.",
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AU - Spratlen, Miranda J.

AU - Grau-Perez, Maria

AU - Umans, Jason G.

AU - Yracheta, Joseph

AU - Best, Lyle G.

AU - Francesconi, Kevin

AU - Goessler, Walter

AU - Bottiglieri, Teodoro

AU - Gamble, Mary V.

AU - Cole, Shelley A.

AU - Zhao, Jinying

AU - Navas Acien, Ana

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N2 - 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.

AB - 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.

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