Abstract

Background: Animal studies show that perfluoroalkyl substances contribute to type 2 diabetes pathogenesis, even at low levels of exposure. However, evidence from human studies is inconclusive and largely based on cross-sectional studies in adults. We examined the associations between exposure to perfluorooctanoic acid (PFOA) and measures of glucose metabolism among Hispanic children at risk for type 2 diabetes. Methods: Overweight and obese Hispanic children were recruited from urban Los Angeles (N=312, age 7-15 years). All children underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT). Insulin sensitivity was assessed by the Composite Insulin Sensitivity Index (ISIcomposite), and insulin resistance was assessed by the homeostatic model of insulin resistance (HOMA-IR). Plasma levels of PFOA were measured using high resolution mass spectrometry. Multiple linear regression models were used to assess the association between PFOA plasma concentrations and measures of insulin sensitivity and resistance after adjusting for covariates including age, sex, socioeconomic status, pubertal status, and body mass index. Results: Each two-fold increase in plasma PFOA was associated with 19.0% increase in HOMA-IR (95% CI: 9.2, 29.8%; p<0.001) and a 13.1% decrease in ISIcomposite (95% CI: -19.8, -5.7%). Plasma PFOA concentrations were also positively associated with fasting glucose and fasting insulin as well as two-hour post OGTT glucose and insulin measures. The effects of PFOA on HOMA-IR and ISIcomposite were similar among boys and girls (both p > 0.2). Conclusion: Our results indicated that childhood exposure to PFOA is associated with impaired glucose metabolism in overweight and obese Hispanic youth. Future work is required to elucidate underlying biological mechanisms between PFOA and glucose metabolism.

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