Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial

Susanna D. Mitro, Jinxi Liu, Lindsay M. Jaacks, Abby F. Fleisch, Paige L. Williams, William C. Knowler, Blandine Laferrère, Wei Perng, George A. Bray, Amisha Wallia, Marie France Hivert, Emily Oken, Tamarra M. James-Todd, Marinella Temprosa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. Methods: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. Results: Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (β = 0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (−0.08 [95%CI: 0.03, −0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with −0.13 [95%CI: 0.04, −0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. Conclusions: PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.

Original languageEnglish (US)
Article number113680
JournalInternational Journal of Hygiene and Environmental Health
StatePublished - Mar 2021


  • Metabolomics
  • PFAS
  • Type 2 diabetes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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