The effects of per- and polyfluoroalkyl substances (PFASs) on type 2 diabetes (T2D) remain unclear. We aimed to explore the effects of PFASs exposure on glucose metabolism disorders in older adults. We enrolled 704 elderly individuals aged over 65 years from Wuhan, China. Plasma concentrations of 12 PFASs were measured using liquid chromatography-mass spectrometry. Generalized linear models and quantile-based g computation (qgcomp) were employed to evaluate the effects of individual and combined PFAS exposures on T2D risk. Additionally, a meta-analysis was conducted to consolidate findings reported in the literature for validation purposes. The detection rate of all 12 PFASs exceeded 80%, with median concentrations ranging from 0.01 to 15.22 ng/mL. Single exposure analysis revealed an inverse association between perfluorododecanoic acid (PFDoA) and impaired fasting glucose (IFG), as well as between PFDoA, perfluoroundecanoic acid (PFUdA), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA) and T2D risk (P < 0.05). Quantile-based g-computation analysis showed an inverse association between the PFAS mixture and IFG and T2D risk, although these associations lacked statistical significance. PFDA exhibited the greatest weight in the negative associations with IFG and T2D. Meta-analysis demonstrated an inverse association between PFDA and PFUdA and T2D risk, and PFOA demonstrated an inverted U-shaped nonlinear dose-response relationship with the risk of T2D (P = 0.026). The potential impact of PFAS exposure on glucose metabolism merits attention, underscoring the need for a thorough comprehension of the biological mechanisms underlying PFAS-mediated metabolic effects to facilitate precise risk assessment.
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