Structure-based investigation on the association between perfluoroalkyl acids exposure and both gestational diabetes mellitus and glucose homeostasis in pregnant women

Background: Biomonitoring studies have shown the presence of structurally diverse perfluoroalkyl acids (PFAAs) in humans but only a few studies are available regarding the differential structural effects of PFAAs on human health. Objective: The specific association between different structural PFAAs and both gestational diabetes mellitus (GDM) and glucose homeostasis in pregnant women was investigated. Methods: A prospective nested case-control study including 439 women was conducted during 2013-2015 in Beijing, China. First trimester maternal serum was collected and analyzed for 25 diverse PFAAs with varying carbon chain lengths, linear/branched isomers and carboxylate or sulfonate functional groups. The analyzed PFAAs were grouped into different exposure variables depending on structure characteristics. GDM cases were diagnosed at 24-28 weeks of gestation and individually matched in a 1: 2 ratio to controls. Conditional logistic and linear regression was used to evaluate the association between structurally grouped PFAAs and both GDM risk and glucose homeostasis parameters. Results: Among the 25 PFAAs, 12 perfluoroalkyl carboxylates (PFCAs) and 8 perfluoroalkyl sulfonates (PFSAs) were detected in > 55.0% of samples and were respectively grouped into different structural groups. The structural-based effect was observed for PFCAs, where short-chain (C4-C7) PFCAs continuous level was significantly associated with GDM with an estimated odds ratio (OR) of 1.99 (95% CI: 1.29, 3.09), and the multivariable-adjusted ORs (95% CI) of GDM for increasing tertiles of short-chain PFCAs were 1.00 (ref.), 1.82 (0.80, 4.16) and 3.01 (1.31, 6.94), P trend = 0.011. Additionally, increased concentration of short-chain PFCAs was significantly associated with higher postprandial glucose levels (P < 0.05). Non-significant association was observed between structure grouped PFSAs and GDM as well as glucose homeostasis. Conclusion: This investigation suggests a structure-specific association between short-chain PFCAs exposure and both GDM risk and impaired glucose homeostasis in pregnant women. These findings warrant further investigation with larger samples and a wide range of short-chain PFCAs exposure.