Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis

• Type of Material: Article
• Authors: Tanya L. Alderete, University of Colorado Boulder; Ran Jin, University of Southern California; Douglas Walker, Emory University; Damaskini Valvi, Harvard University; Zhanghua Chen, University of Southern California; Dean P Jones, Emory University; Cheng Peng, University of Southern California; Frank D. Gilliland, University of Southern California; Kiros Berhane, University of Southern California; David V. Conti, University of Southern California; Michael I. Goran, Children’s Hospital of Los Angeles; Lida Chatzi, University of Southern California
• Language: English
• Date: 2019-05-01
• Publisher: PERGAMON-ELSEVIER SCIENCE LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Authors. Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.envint.2019.02.047
• Title of Journal or Parent Work: Environment International
• Volume: 126
• Start Page: 445
• End Page: 453
• Grant/Funding Information: This work was supported by NIH P30ES007048 (Chatzi, Gilliland); NIEHS R21ES028903 (Chatzi); NIH R01DK59211 (Goran); NIEHS R00ES027853 (Alderete); NIEHS F32ES029828 (Jin); NIEHS K99ES027870 (Chen); R01-MH107205 (Jones and Walker); P30ES019776 (Jones and Walker); U2CES026560 (Jones and Walker); T32ES012870 (Walker); P01CA196569; R01CA140561; R01 ES016813 (Conti).
• Keywords: EARLY-LIFE EXPOSURE; BETA-CELL FUNCTION; FATTY-ACIDS; PUBERTAL CHANGES; Metabolomics; Children; Environmental Sciences & Ecology; CHEMICALS; Type 2 diabetes; LONGITUDINAL ASSOCIATIONS; Glucose metabolism; INSULIN-RESISTANCE; BRANCHED-CHAIN; MASS-SPECTROMETRY; Life Sciences & Biomedicine; AMINO-ACIDS; Environmental Sciences; Perfluoroalkyl substances; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Environmental Sciences

Abstract

Objective: To examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children. Methods: Forty overweight and obese Hispanic children (8–14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1–3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry. Multiple linear regression models were used to assess the association between baseline PFASs and changes in glucose homeostasis over follow-up. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with plasma PFASs concentrations. We performed a structural integrated analysis aiming to characterize the joint impact of all factors and to identify latent clusters of children with alterations in glucose homeostasis, based on their exposure and metabolomics profile. Results: Each ln (ng/ml) increase in PFOA and PFHxS concentrations was associated with a 30.6 mg/dL (95% CI: 8.8–52.4) and 10.2 mg/dL (95% CI: 2.7–17.7) increase in 2-hour glucose levels, respectively. A ln (ng/ml) increase in PFHxS concentrations was also associated with 17.8 mg/dL increase in the glucose area under the curve (95% CI: 1.5–34.1). Pathway enrichment analysis showed significant alterations of lipids (e.g., glycosphingolipids, linoleic acid, and de novo lipogenesis), and amino acids (e.g., aspartate and asparagine, tyrosine, arginine and proline) in association to PFASs exposure. The integrated analysis identified a cluster of children with increased 2-h glucose levels over follow up, characterized by increased PFAS levels and altered metabolite patterns. Conclusions: This proof-of-concept analysis shows that higher PFAS exposure was associated with dysregulation of several lipid and amino acid pathways and longitudinal alterations in glucose homeostasis in Hispanic youth. Larger studies are needed to confirm these findings and fully elucidate the underlying biological mechanisms.