Associations between per- and polyfluoroalkyl substances and type 2 diabetes: The modifying effects of lifestyle and genetic risk
By Xu Cheng, Fei Wang, Jin Zhang, Yu Wang, Lu Liu, Lin Liu, Hong Guo, Junya Gao, Yafei Tan, and Meian He
J Hazard Mater
August 23, 2025
DOI: 10.1016/j.jhazmat.2025.139644
The longitudinal association between per- and polyfluoroalkyl substances (PFASs) and type 2 diabetes (T2D) remains elusive. We conducted a nested case-control study, including 985 incident diabetes cases and 985 matched controls to explore the association of PFASs exposure with T2D. Serum concentrations of 30 PFASs were measured. Odds ratios (ORs) were estimated by conditional logistic regression. PFAS mixtures effects were assessed using BKMR, WQSR, and Qgcomp. We assessed the roles of lifestyle score and polygenic risk score in PFASs-T2D association by multiplicative/additive interaction. PFOA and PFNA were positively associated, but L-PFHxS and L-PFOS were negatively associated with T2D. Compared with the extreme tertiles, the OR (95 % CI) was 1.39 (1.09-1.78) for PFOA; 1.32 (1.02-1.71) for PFNA; 0.77 (0.60-0.99) for L-PFHxS; 0.71 (0.55-0.92) for L-PFOS. PFBA and PFHpA (detected/not-detected) were positively associated with T2D. Positive associations of PFBA, PFOA, and PFNA with T2D were only observed in females, whereas negative associations of L-PFHxS and L-PFOS were observed in males. PFASs mixtures were not associated with T2D, but independent associations were found between PFOA, PFNA, L-PFHxS, and L-PFOS with T2D. Additive interactions were observed between PFASs exposure and lifestyle/genetic susceptibility. Poor lifestyle and genetic risk may amplify the adverse effects of PFASs.
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