Exposure to novel and legacy per- and polyfluoroalkyl substances (PFASs) and associations with type 2 diabetes: A case-control study in East China.

Associations between per- and polyfluoroalkyl substances (PFASs) and the incidence of type 2 diabetes are controversial in epidemiological studies. In addition, limited data are available for assessing the health effects of novel PFAS alternatives. Our study evaluated the effects of PFAS exposure on type 2 diabetes by estimating the associations of PFASs in human serum with the risk of type 2 diabetes and levels of glycemic biomarkers and lipid fractions. The case-control study consisted of 304 participants from Shandong Province, East China, half of which were diagnosed with type 2 diabetes. Logistic regression showed that most PFASs were inversely associated with the risk of type 2 diabetes after adjusting for age, sex, and body mass index. However, concentrations of perfluorooctanoic acid (PFOA) in the control group were positively associated with fasting plasma glucose levels (β = 0.04, 95% confidence interval (CI): 0.0003, 0.08), which may promote the development of type 2 diabetes. Furthermore, each log-unit increase in the concentrations of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (Cl-PFESA) were associated with a total cholesterol increase (i.e., 17.49% (95% CI: 0.93%, 34.90%), 17.49% (95% CI: 4.71%, 31.83%), and 17.49% (95% CI: 4.71%, 31.83%), respectively). Positive associations were also observed between PFNA, PFUnDA, perfluorooctane sulfonate (PFOS), and 6:2 Cl-PFESA and low-density lipoprotein cholesterol. However, no associations between PFASs and hemoglobin A1c, triglycerides, or high-density lipoprotein cholesterol reached statistical significance, nor associations between PFAS mixtures and outcomes of interest. In conclusion, the significant correlations between serum PFASs and glycemic biomarkers and lipid fractions indicated that PFAS exposure may be a potential diabetogenic factor. To the best of our knowledge, this is the first study to assess the associations between novel Cl-PFESAs and type 2 diabetes, although the inverse associations observed require clarification in future studies.