Exposure to Perfluoroalkyl Substances and Longitudinal Alterations in Glucose Metabolism among Overweight and Obese Hispanic Children: A Metabolomics Approach

摘要

Background: Animal studies have shown that early life exposure to perfluoroalkyl substances (PFASs) may disturb glucose metabolism. Human evidence is inconsistent and no previous study has examined the prospective associations between exposure to PFASs and repeated measures of glucose metabolism among Hispanic children. Methods: Overweight and obese Hispanic children (8-14 years) from urban Los Angeles (n=40) underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and follow-up visits (range: 1-3 years). PFASs [perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS)] and untargeted metabolic profiling (～4000 metabolites) of baseline serum samples were measured by high resolution mass spectometry. Linear regression models were used to assess associations between baseline PFASs and changes in metabolic outcomes over follow-up after adjusting for confounders including age, sex, adiposity and puberty status. Network correlation and cluster analyses identified metabolic responses to PFASs that were characterized by pathway enrichment analysis using Mummichog. Results: Each In-unit increase in PFOA and PFHxS concentrations was associated with a 26.3 mg/dL (95% CI: 4.9-47.7) and 9.6 mg/dL (95% CI: 1.7-17.6) increase in 2-hour glucose levels, respectively. A In-unit increase in PFHxS concentrations was also associated with a 18.2 mg/dL increase in the glucose area under the curve (95% CI: 2.6-33.8). Metabolome-wide associations identified 615, 974 and 132 metabolic features associated with PFOA, PFOS and PFHxS, respectively after correcting for multiple comparisons. Pathway analysis showed significant alterations of methionine and cysteine metabolism, hexose phosphorylation, and glycerophospholipid and glycosphingolipid metabolism that were associated with PFASs exposure. Conclusions: This first pilot analysis provides evidence that PFASs exposure may exert diabetogenic effects in Hispanic youth.