Association between per- and polyfluoroalkyl substances exposure and risk of diabetes: a systematic review and meta-analysis

Background Emerging evidence suggests that per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors and may contribute to the etiology of diabetes. Objectives This study aimed to systematically review the epidemiological evidence on the associations of PFAS with mortality and morbidity of diabetes and to quantitatively evaluate the summary effect estimates of the existing literature. Methods We searched three electronic databases for epidemiological studies concerning PFAS and diabetes published before April 1, 2022. Summary odds ratio (OR), hazard ratio (HR), or beta and their 95% confidence intervals (CIs) were respectively calculated to evaluate the association between PFAS and diabetes using random-effects model by the exposure type, and dose-response meta-analyses were also performed when possible. We also assessed the risk of bias of the studies included and the confidence in the body of evidence. Results An initial literature search identified 1969 studies, of which 22 studies were eventually included. The meta-analyses indicated that the observed statistically significant PFAS-T2DM associations were consistent in cohort studies, while the associations were almost non-significant in case-control and cross-sectional studies. Dose-response meta-analysis showed a "parabolic-shaped" association between perfluorooctanoate acid (PFOA) exposure and T2DM risk. Available evidence was rated with "low" risk of bias, and the level of evidence for PFAS and incident T2DM was considered "moderate". Conclusions Our findings suggest that PFAS exposure may increase the risk of incident T2DM, and that PFOA may exert non-monotonic dose-response effect on T2DM risk. Considering the widespread exposure, persistence, and potential for adverse health effects of PFAS, further cohort studies with improvements in expanding the sample size, adjusting the covariates, and considering different types of PFAS exposure at various doses, are needed to elucidate the putative causal associations and potential mode of action of different PFAS on diabetes. Impact Statement A growing body of evidence suggests that per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors and may contribute to the development of diabetes. However, epidemiological evidence on the associations of PFAS and diabetes is inconsistent. We performed this comprehensive systematic review and meta-analysis to quantitatively synthesize the evidence. The findings of this study suggest that exposure to PFAS may increase diabetes risk among the general population. Reduced exposure to these "forever and everywhere chemicals" may be an important preventative approach to reducing the risk of diabetes across the population.