A1 Refereed original research article in a scientific journal
Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes - A nested case-control study
Authors: Schillemans Tessa, Shi Lin, Donat-Vargas Carolina, Hanhineva Kati, Tornevi Andreas, Johansson Ingegerd, Koponen Jani, Kiviranta Hannu, Rolandsson Olov, Bergdahl Ingvar A, Landberg Rikard, Åkesson Agneta, Brunius Carl
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Publication year: 2021
Journal: Environment International
Journal name in source: ENVIRONMENT INTERNATIONAL
Journal acronym: ENVIRON INT
Article number: ARTN 106180
Volume: 146
Number of pages: 10
ISSN: 0160-4120
eISSN: 1873-6750
DOI: https://doi.org/10.1016/j.envint.2020.106180
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/51150369
Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations.We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Vasterbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D.PFAS levels correlated with 171 metabolite features (0.16 <= vertical bar r vertical bar <= 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1-0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3-2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
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