Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis. (May 2019)

• Record Type: Journal Article
• Authors: Alderete, Tanya L.; Jin, Ran; Walker, Douglas I.; Valvi, Damaskini; Chen, Zhanghua; Jones, Dean P.; Peng, Cheng; Gilliland, Frank D.; Berhane, Kiros; Conti, David V.; Goran, Michael I.; Chatzi, Lida
• Is Part Of: Environment international. Volume 126(2019)
• Page Start: 445
• Page End: 453
• Publication Date: 2019-05
• Subjects: PFASs perfluoroalkyl substances -- PFHxS perfluorohexane sulfonic acid -- PFOA perfluorooctanoic acid -- PFOS perfluorooctane sulfonate -- EDCs endocrine-disrupting chemicals -- PPARs peroxisome proliferator activated receptors -- OGTT oral glucose tolerance test -- HOMA-IR homeostatic model assessment for insulin resistance -- AUC area under the curve -- BMI body mass index -- DEXA dual-energy X-ray absorptiometry -- FDR false discovery rate -- HRM high-resolution metabolomics; Perfluoroalkyl substances -- Type 2 diabetes -- Glucose metabolism -- Metabolomics -- Children; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2019.02.047
• Languages: English
• ISSNs: 0160-4120

Abstract

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. Highlights: PFASs induce diabesogenic effects in animal models but human evidence is limited. Repeated 2-hour oral glucose tolerance tests were performed in Hispanic children. Plasma PFASs concentrations and metabolomics profiles were measured at baseline. Higher PFASs exposure was associated with alterations in glucose homeostasis. Several lipid and amino acid pathways were associated with PFASs exposure.