Exposure to Perfluoroalkyl Substances and Glucose Homeostasis in Youth

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS), a prevalent class of persistent pollutants, may increase the risk of type 2 diabetes. OBJECTIVE: We examined associations between PFAS exposure and glucose metabolism in youth. METHODS: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; [Formula: see text]) participated in annual visits for an average of [Formula: see text]. Generalizability of findings were tested in young adults from the Southern California Children’s Health Study (CHS; [Formula: see text]) who participated in a clinical visit with a similar protocol. At each visit, oral glucose tolerance tests were performed to estimate glucose metabolism and [Formula: see text] function via the insulinogenic index. Four PFAS were measured at baseline using liquid chromatography–high-resolution mass spectrometry; high levels were defined as concentrations [Formula: see text] percentile. RESULTS: In females from the SOLAR, high perfluorohexane sulfonate (PFHxS) levels ([Formula: see text]) were associated with the development of dysregulated glucose metabolism beginning in late puberty. The magnitude of these associations increased postpuberty and persisted through 18 years of age. For example, postpuberty, females with high PFHxS levels had [Formula: see text] higher 60-min glucose (95% CI: [Formula: see text]; [Formula: see text]), [Formula: see text] higher 2-h glucose (95% CI: [Formula: see text]; [Formula: see text]), and 25% lower [Formula: see text] function ([Formula: see text]) compared with females with low levels. Results were largely consistent in the CHS, where females with elevated PFHxS levels had [Formula: see text] higher 60-min glucose (95% CI: [Formula: see text]; [Formula: see text]) and [Formula: see text] higher 2-h glucose, which did not meet statistical significance (95% CI: [Formula: see text]; [Formula: see text]). In males, no consistent associations between PFHxS and glucose metabolism were observed. No consistent associations were observed for other PFAS and glucose metabolism. DISCUSSION: Youth exposure to PFHxS was associated with dysregulated glucose metabolism in females, which may be due to changes in [Formula: see text] function. These associations appeared during puberty and were most pronounced postpuberty. https://doi.org/10.1289/EHP9200