Associations between PFAS exposure and glycemic markers in nondiabetic women of reproductive age: NHANES 2003–2018

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Background . Per- and polyfluoroalkyl substances (PFAS) are suspected to affect metabolic health, but their relationship with glycemic markers remains unclear, especially in reproductive-aged women, which are influenced by hormonal regulation. This study examined the associations between PFAS exposure and the levels of glycemic markers in nondiabetic women. Methods . Data from the 2003–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed using general linear regression to assess the associations of individual PFAS compounds with fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and logistic regression for impaired glucose regulation (IGR) risk. Restricted cubic splines were used to explore dose–response relationships, whereas the qgcomp and weighted quantile sum regression (WQS) models were used to evaluate the cumulative effects of PFAS mixtures. Results . Among 2,003 women, including 1,013 women of reproductive age. In reproductive-age women, PFOA, PFOS, PFHxS, PFUnDA were significantly negatively associated with HbA1c. Additionally, significantly negative associations with FPG were observed for PFOA and PFNA. Logistic regression analysis revealed significant inverse associations with IGR risk for PFOA and PFNA. Among nonreproductive-aged women, Me-PFOSA-AcOH was inversely associated with FPG, whereas PFNA was positively associated with HbA1c, suggesting potential age-specific differences in PFAS effects. In the qgcomp and WQS models, PFOS, PFUnDA, and Me-PFOSA-AcOH were identified as significant contributors to the observed negative associations with glycemic markers. Conclusions . Mixed PFAS exposure is significantly and inversely associated with glycemic markers in reproductive-aged women, albeit with modest effect sizes. Given the reproductive health risks of PFAS, cohort studies and targeted exposure management strategies are essential to safeguard this sensitive population.