Temporal changes in per and polyfluoroalkyl substances and their associations with type 2 diabetes.

We assessed temporal changes of PFAS and associations with T2DM over a period of 30 years in a nested case-control study with repeated measurements. Logistic regression was used to assess associations between 11 PFAS and T2DM at five time-points in 116 cases and 139 controls (3 pre- and 2 post-diagnostic time-points in cases). Mixed linear models were applied to assess if changes in PFAS were related to T2DM status. In the pre-diagnostic time-point T3 (2001), future cases had higher concentrations of PFHpA, PFNA, PFHxS and PFHpS compared to controls. In the post-diagnostic time point T5 (2015/16), PFNA and PFOS were higher in prevalent cases. PFHxS and PFHpS were positively associated with future T2DM at the pre-diagnostic time-point T3, whereas PFTrDA were inversely associated with future T2DM at T1 (1986/87) and prevalent T2DM at T4 (2007/8). Temporal changes in PFAS across the study period showed that cases experienced a greater increase in pre-diagnostic concentrations of PFHpA, PFTrDA, PFHxS and PFOSA, as well as a larger post-diagnostic decrease in PFOSA, compared to controls. This study is the first to show that temporal changes in PFAS are associated with T2DM status for certain PFAS, and associations between PFAS and T2DM vary according to sample year.