Exposure to isomers of per- and polyfluoroalkyl substances increases the risk of diabetes and impairs glucose-homeostasis in Chinese adults: Isomers of C8 health project.

Per- and polyfluoroalkyl substances (PFAS) exposure has been linked to diabetes, but evidence on the association of isomers of PFAS with type 2 diabetes (T2D) remains scant. This population based cross-sectional study aimed to investigate associations between serum PFAS isomers, glucose-homeostasis markers and T2D, adjusted for multiple potential confounders. We used data from "Isomers of C8 Health Project in China" from July 2015 to October 2016. A total of 10 PFAS including isomers of PFOS and PFOA were measured in serum of 1045 Chinese adults. Fasting blood glucose, fasting insulin, homeostasis model of insulin (HOMA-IR) and beta cell function (HOMA-β) were considered as markers of glucose-homeostasis. We found significant positive associations between serum PFAS isomers and glucose-homeostasis markers, namely, fasting blood glucose, fasting insulin and HOMA-IR. Per log-unit increase in branched (br)-PFOS concentration was associated with increased fasting blood glucose (β = 0.25, 95% CI: 0.18, 0.33), fasting insulin (β = 2.19, 95% CI: 1.44, 2.93) and HOMA-IR (β = 0.69, 95% CI: 0.50, 0.89). As compared to br-PFOS, linear (n)-PFOS and -PFOA showed lesser significant associations with glucose-homeostasis makers. Further, exposure to all PFAS including isomeric PFOS, PFOA and PFHxS increased the risk of T2D with br-PFOS exhibiting the highest risk (OR = 5.41, 95% CI: 3.68-7.96). The associations were stronger among women than men. In conclusion, chronic exposure to PFAS isomers was associated with impaired glucose-homeostasis and may increase the prevalence of T2D in Chinese adults. Given the ubiquity of PFAS in the environment and the public health burden of T2D, future studies are warranted to corroborate the findings.

Zeeshan M ，Zhang YT ，Yu S ，Huang WZ ，Zhou Y ，Vinothkumar R ，Chu C ，Li QQ ，Wu QZ ，Ye WL ，Zhou P ，Dong P ，Zeng XW ，Hu LW ，Yang BY ，Shen X ，Zhou Y ，Dong GH ... -  《-》

Isomers of per- and polyfluoroalkyl substances and uric acid in adults: Isomers of C8 Health Project in China.

Greater levels of serum per- and polyfluoroalkyl substances (PFAS) are known to be associated with higher uric acid which itself leads to a number of chronic diseases. However, whether this association varies across PFAS isomers which recently have been found to be associated with human health remains unknown. To address this research gap, we explored isomer-specific associations between serum PFAS and uric acid in Chinese adults. We conducted a cross-sectional study of associations between serum PFAS isomer and serum uric acid in 1612 participants from the Isomer of C8 Health Project. We used multivariable linear and logistic regression models to analyze serum isomers of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and other PFASs as continuous and categorical predictors of uric acid, adjusted for confounders. The association was also stratified by kidney function stage based on estimated glomerular filtration rate (GF-1, GF-2, GF-3a, and GF-3b/4). We found positive associations between serum PFAS isomer concentrations and uric acid. Uric acid levels were greater for each log-unit increase in branched PFOA (β = 0.30, 95% CI: 0.21, 0.40), linear PFOA (β = 0.18, 95% CI: 0.09, 0.26), branched PFOS (β = 0.09, 95% CI: 0.02, 0.17) and linear PFOS (β = 0.06, 95% CI: -0.01, 0.14) concentration. The associations between PFAS and uric acid showed an inverted 'U' shaped pattern across kidney function stages. For example, uric acid level was greater with each log-unit increase in total-PFOA among GF-1 (β = 0.21, 95% CI: 0.06, 0.37), this relationship was greater in GF-3a (β = 0.49, 95% CI: 0.09, 0.89) and decreased in GF-3b/4 (β = -0.22, 95% CI: -0.83, 0.39). We also found the odds of hyperuricemia increased linearly with increasing branched PFOA in quartiles (odds ratio = 2.67, 95% CI: 1.86, 3.85 at the highest quartile). We report novel results in which PFAS associations with uric acid varied according to isomer and adult kidney function. Besides, our findings are consistent with previous epidemiologic studies in finding a positive association between serum PFAS concentrations and serum uric acid, especially for PFOA. Our results indicate that more research is needed to more clearly assess the impact of PFAS isomers on human health, which will help to refine regulation policies for PFAS.

Zeng XW ，Lodge CJ ，Dharmage SC ，Bloom MS ，Yu Y ，Yang M ，Chu C ，Li QQ ，Hu LW ，Liu KK ，Yang BY ，Dong GH ... -  《-》

Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden.

Per- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis. In 2373 subjects aged 45-75 years from the EpiHealth study, three PFAS; perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were analyzed in plasma together with information on prevalent diabetes. Participants in the PIVUS study (n = 1016 at baseline, all aged 70 years) were followed over 10 years regarding changes in plasma levels of six PFAS; PFHxS, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and changes in plasma levels of fasting glucose. In the EpiHealth study, no overall associations could be observed between the levels of PFOA, PFOS or PFHxS and prevalent diabetes. However, there was a significant sex-interaction for PFOA (p = 0.02), and an inverse association could be seen between PFOA (on a SD-scale) and prevalent diabetes in women only (OR: 0.71, 95% CI: 0.52, 0.96, p-value: 0.02). This association showed a non-monotonic dose-response curve. In the PIVUS study, inverse relationships could be observed between the changes in levels (ln-transformed) of PFOA and PFUnDA vs the change in fasting glucose levels (ln-transformed) over 10 years (p = 0.04 and p = 0.02, respectively). As in EpiHealth, these inverse associations were significant only in women (PFOA: β: -0.03, p = 0.02, PFUnDA: β: -0.03, p = 0.03). Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to unfavorable human health, including metabolic disorders such as obesity, diabetes and non-alcoholic fatty liver disease. However, results from in vivo, in vitro and epidemiological studies are incoherent. The aim of the present study was therefore to investigate associations between PFAS and diabetes in a cross-sectional study and glucose levels in a longitudinal study. Results show inverse associations in women only. Results also display non-monotonic dose response curves (i.e., that only low levels of PFOA are related to higher probability of prevalent diabetes). This suggests that sex differences and complex molecular mechanisms may underlie the observed findings. A better understanding of the factors and molecular mechanisms contributing to such differences is recognized as an important direction for future research. PFOA was found to be inversely related to both prevalent diabetes and changes in plasma glucose levels among women only. Thus, our findings suggest there are sex differences in the inverse relationship of PFOA and type 2 diabetes and glucose levels.

Dunder L ，Salihovic S ，Elmståhl S ，Lind PM ，Lind L ... -  《-》

Associations between both legacy and alternative per- and polyfluoroalkyl substances and glucose-homeostasis: The Isomers of C8 health project in China.

Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

Zhang YT ，Zeeshan M ，Su F ，Qian ZM ，Dee Geiger S ，Edward McMillin S ，Wang ZB ，Dong PX ，Ou YQ ，Xiong SM ，Shen XB ，Zhou PE ，Yang BY ，Chu C ，Li QQ ，Zeng XW ，Feng WR ，Zhou YZ ，Dong GH ... -  《-》

Plasma Concentrations of Per- and Polyfluoroalkyl Substances at Baseline and Associations with Glycemic Indicators and Diabetes Incidence among High-Risk Adults in the Diabetes Prevention Program Trial.

Cardenas A ，Gold DR ，Hauser R ，Kleinman KP ，Hivert MF ，Calafat AM ，Ye X ，Webster TF ，Horton ES ，Oken E ... -  《-》