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Environ Int. 2019 Mar 4;126:445-453. doi: 10.1016/j.envint.2019.02.047. [Epub ahead of print]

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

Author information

1
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States. Electronic address: tanya.alderete@colorado.edu.
2
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: jinr@usc.edu.
3
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: douglas.walker@mssm.edu.
4
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States. Electronic address: dvalvi@hsph.harvard.edu.
5
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: zhanghuc@usc.edu.
6
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, United States. Electronic address: dpjones@emory.edu.
7
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: chengpen@usc.edu.
8
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: gillilan@usc.edu.
9
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: kiros@usc.edu.
10
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: dconti@med.usc.edu.
11
Department of Pediatrics, Children's Hospital of Los Angeles, The Saban Research Institute, United States. Electronic address: goran@usc.edu.
12
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: chatzi@usc.edu.

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.

KEYWORDS:

Children; Glucose metabolism; Metabolomics; Perfluoroalkyl substances; Type 2 diabetes

PMID:
30844580
DOI:
10.1016/j.envint.2019.02.047
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