Polyfluoroalkyl substances and altered glucose homeostasis in adolescents following bariatric surgery

Abstract Objectives Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to polyfluoroalkyl substance (PFAS) before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes. Design This is an observational cohort study. Methods Adolescents (n = 186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery study were included. Eight-PFAS congeners were measured in plasma before surgery. Linear and logistic regressions were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Linear mixed models were used to examine the longitudinal associations between PFAS and outcomes measured at baseline and 6-, 12-, 36-, and 60-months post-surgery. Polyfluoroalkyl substance mixture associations at each visit were assessed using quantile g-computation. All models were adjusted for demographics, study site, and use of diabetes medication. Results Perfluorohexanesulfonic acid (PFHxS) was associated with greater increases in fasting glucose and HbA1c in the 1- to 5-year post-operative period: for instance, a PFHxS level of 1.95 log2-ng/mL was associated with a 3.30 mg/dL (95% CI: 1.23, 5.37) increase over 4 years, while a PFHxS level of −0.16 log2-ng/mL was associated with a 1.19 mg/dL (95% CI: −0.91, 3.29) increase. PFHxS, perfluoroheptanesulfonic acid, and perfluoroheptanoic acid were positively associated with insulin and HOMA-IR at baseline, but not in the 1- to 5-year post-operative period. Each simultaneous quartile increase in the PFAS mixture was associated with higher insulin and HOMA-IR at baseline, but this association did not persist at follow-up visits. Conclusions Perfluorohexanesulfonic acid exposure may attenuate improvement in fasting glucose and HbA1c after bariatric surgery. Improvements in insulin resistance after surgery were not associated with PFAS exposure.