Targeted metabolomics to understand the association between arsenic metabolism and diabetes-related outcomes: Preliminary evidence from the Strong Heart Family Study.
American Indians
Metabolomics
arsenic metabolism
diabetes
one carbon metabolism
Journal
Environmental research
ISSN: 1096-0953
Titre abrégé: Environ Res
Pays: Netherlands
ID NLM: 0147621
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
06
06
2018
revised:
02
09
2018
accepted:
25
09
2018
pubmed:
14
10
2018
medline:
1
10
2019
entrez:
14
10
2018
Statut:
ppublish
Résumé
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. The mechanism behind these conflicting associations is unclear; we hypothesized the one-carbon metabolism (OCM) pathway may play a role. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 30316100
pii: S0013-9351(18)30520-6
doi: 10.1016/j.envres.2018.09.034
pmc: PMC6298442
mid: NIHMS1509386
pii:
doi:
Substances chimiques
Arsenic
N712M78A8G
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
146-157Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL041642
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL041654
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK091369
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES025216
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL090863
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL041652
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES010349
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109319
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109284
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL065521
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007141
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109282
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES009089
Pays : United States
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ID : F31 ES027796
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109315
Pays : United States
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ID : R01 DK107532
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109301
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL065520
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES021367
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.