PFAS and Altered Glucose Homeostasis in Adolescents following Bariatric Surgery

Objective Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to PFAS before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes. Design Observational cohort study. Methods Adolescents (n=186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (LABS) study were included. Eight PFAS congeners were measured in plasma before surgery. Linear and logistic regression were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, HbA1c, and HOMA-IR. Linear mixed models were used to examine the longitudinal associations between PFAS and outcomes measured at baseline and 6-, 12-, 36-, 60- months post-surgery. PFAS mixtures associations at each visit were assessed using quantile g-computation. All models were adjusted for demographics, study site, and use of diabetes medication. Results PFHxS was associated with greater increases in fasting glucose and HbA1c in the one-to-five year post-operative period: for instance, a PFHxS level of 1.95 log2-ng/mL was associated with a 3.30mg/dL (95%CI:1.23,5.37) increase over four 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, PFHpS, and PFHpA were positively associated with insulin and HOMA-IR at baseline, but not in the one-to-five-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 PFHxS exposure may attenuate improvement in fasting glucose and HbA1c after bariatric surgery. Improvements in insulin resistance after surgery were not associated with PFAS exposure.