Associations of per- and polyfluoroalkyl substances exposure with gestational diabetes mellitus and effect modification by vitamin D status

Per- and polyfluoroalkyl substances (PFAS) could disrupt glucose homeostasis by inducing oxidative stress, inflammatory responses, and endocrine disruption. However, the association between PFAS and gestational diabetes mellitus (GDM) and its subtypes remains controversial. Additionally, the effect modification by vitamin D on these associations is yet to be elucidated. Data from 746 pregnant women in a prospective birth cohort in Henan Province, China, were used. Eight PFAS with detection rates > 80% were included. GDM was diagnosed by oral glucose tolerance test and classified into isolated fasting hyperglycemia (IFH), isolated postprandial hyperglycemia (IPH), and combined hyperglycemia (CH). Logistic regression and weighted quantile sum (WQS) models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for the associations of individual PFAS and their mixture with GDM and its subtypes, as well as the modifying effect of vitamin D status. Of 746 women, 183 (24.53%) developed GDM. Higher concentrations of PFHpS (OR = 1.19, 95% CI: 1.07–1.32), PFPeS (OR = 1.23, 95% CI: 1.09–1.38), and PFHxA (OR = 1.13, 95% CI: 1.02–1.25) were positively associated with GDM risk. When stratified by GDM subtypes, positive associations of PFHpS and PFPeS with GDM were restricted to women with IPH. WQS regression showed a positive association between PFAS mixture and GDM risk (OR = 1.50, 95% CI: 1.04–2.16), with PFHpS as the top contributor. Regarding vitamin D modification, PFOS (OR = 1.12, 95% CI: 1.01–1.25), PFHpS (OR = 1.22, 95% CI: 1.09–1.37) and PFPeS (OR = 1.26, 95% CI: 1.12–1.42) were positively associated with GDM in vitamin D-deficient group, but not in non-deficient group. PFAS exposure during pregnancy increased GDM risk, particularly for the IPH subtype. Maternal vitamin D concentrations may modify the association between PFAS exposure and GDM, although this potential effect modification should be interpreted cautiously given the small non-deficient subgroup.