Per- and polyfluoroalkyl substances and type 2 diabetes risk: Evidence from metabolomics and triglyceride-glucose index-related pathways.

Sex-Specific Associations Between Per- and Polyfluoroalkyl Substances and the Risk of Type 2 Diabetes: The Role of Genetic Susceptibility and Lipid Metabolism

The observed effect modification by CYP19A1 rs2414098 suggests that hormonal pathways may contribute to the sex-specific associations, although this hypothesis requires confirmation in studies with direct hormone measurements and experimental validation.

Integrating Lipid Metabolomics and Epidemiology: A Mediation Analysis of Blood Lipids between Per- and Polyfluoroalkyl Substances (PFAS) and Renal Impairment.

It is suggested that mixed PFAS exposure, particularly to PFOA and PFHpA, may induce impaired renal function, with increased blood lipids playing an important mediating role.

Associations of per- and polyfluoroalkyl substances (PFAS) exposure with arterial stiffness: Evidence from NHANES 2011-2018.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants linked to various diseases, yet their association with arterial stiffness remains unclear. Using data from 5209 U.S. adults in the National Health and Nutrition Examination Survey (2011-2018), the association between PFAS exposure and estimated pulse wave velocity (ePWV) was investigated via multiple statistical approaches. In single-exposure models, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS), but not perfluorononanoic acid (PFNA), were significantly associated with elevated ePWV. PFOS exhibited a nonlinear dose-response relationship. However, mixture analyses (Weighted Quantile Sum regression and Quantile G-computation models) detected no significant overall mixture effect. Exploratory component rankings and an Extreme Gradient Boosting model interpreted with SHapley Additive exPlanations consistently identified PFOS as the predominant driver. Exploratory mediation analyses suggested that oxidative stress (serum uric acid and gamma-glutamyl transferase [GGT]) and mineral homeostasis (serum calcium) may serve as potential mediating pathways, although the nonspecific signals for uric acid, and inconsistent GGT findings across PFAS congeners warrant cautious interpretation. Subgroup analyses indicated greater susceptibility in females and partnered individuals. Overall, these findings provide hypothesis-generating evidence for potential pathways and offer exploratory insights for prevention, while also highlighting the need for future studies employing more direct measures.

Healthy lifestyle modifies the association between per- and polyfluoroalkyl substances and hyperlipidemia: A propensity score-matched case-control study.

It is demonstrated that adherence to a healthy lifestyle was associated with substantially weaker associations between 6:2 Cl-PFESA and PFDA exposures and hyperlipidemia, highlighting lifestyle modification may serve as a potential public health strategy to reduce environmental metabolic hazards.

Revealing the Link Between Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Stroke: A Comprehensive Epidemiological and Network Toxicology Perspective

Association between plasma levels of per- and polyfluoroalkyl substances and schizophrenia: A case-control study.

Per- and polyfluoroalkyl substances (PFAS) are a class of neurotoxic persistent organic pollutants that may increase the risk of cognitive impairment and dementia, yet their association with schizophrenia (SCZ) remains unclear. This study aimed to investigate the relationship between plasma PFAS levels and the risk of schizophrenia. The concentrations of PFAS in plasma were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). To evaluate the single and combined effects of PFAS exposure on the risk of schizophrenia, we employed multivariable logistic regression, restricted cubic splines (RCS), Bayesian kernel machine regression (BKMR), and generalized weighted quantile sum (gWQS) models. Logistic regression analysis revealed that, compared with the lowest quartile (Q1), the odds ratios (ORs) for PFOS and PFHxS in the highest quartile (Q4) were 0.17 (95% CI:0.09∼0.36) and 0.39 (95% CI:0.21∼0.71), respectively. RCS analysis suggested nonlinear relationships between PFUnDA, PFOS, PFOA, and PFHxS and schizophrenia. In the assessment of mixture exposure effects, the BKMR model indicated an overall negative association between PFAS mixtures and schizophrenia risk, and gWQS analysis further identified PFHxS as the component with the highest weight contribution. Additionally, correlations were observed between the levels of PFUnDA, PFOS, and PFHxS and inflammatory indices in patients with schizophrenia. Future large-scale prospective studies combined with toxicological mechanism research are needed to further validate these findings.