Plasma Concentrations of Per- and Polyfluoroalkyl Substances at Baseline and Associations with Glycemic Indicators and Diabetes Incidence among High-Risk Adults in the Diabetes Prevention Program Trial

Abstract

Background:Several per- and polyfluoroalkyl substances (PFAS) are ubiquitous anthropogenic pollutants almost universally detected in humans. Experimental evidence indicates that PFAS alter glucose metabolism and insulin secretion. However, epidemiological studies have yielded inconsistent results.Objective:We sought to examine associations between plasma PFAS concentrations, glycemic indicators, and diabetes incidence among high-risk adults.Methods:Within the Diabetes Prevention Program (DPP), a trial for the prevention of type 2 diabetes among high-risk individuals, we quantified baseline plasma concentrations of nine PFAS among 957 participants randomized to a lifestyle intervention or placebo. We evaluated adjusted associations for plasma PFAS concentrations with diabetes incidence and key glycemic indicators measured at baseline and annually over up to 4.6 y.Results:Plasma PFAS concentrations were similar to those reported in the U.S. population in 1999–2000. At baseline, in cross-sectional analysis, a doubling in plasma perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) concentrations was associated with higher homeostatic model assessment of insulin resistance (HOMA-IR) [normalβPFOS=0.39; 95% confidence interval (CI): 0.13, 0.66; normalβPFOA=0.64; 95% CI: 0.34, 0.94], β-cell function (HOMA-β) (normalβPFOS=9.62; 95% CI: 1.55, 17.70; normalβPFOA=15.93; 95% CI: 6.78, 25.08), fasting proinsulin (normalβPFOS=1.37 pM; 95% CI: 0.50, 2.25; normalβPFOA=1.71 pM; 95% CI: 0.72, 2.71), and glycated hemoglobin (HbA1c) (normalβPFOS=0.03%; 95% CI: 0.002, 0.07; normalβPFOA=0.04%; 95% CI: 0.001, 0.07). There was no strong evidence of associations between plasma PFAS concentrations and diabetes incidence or prospective changes in glycemic indicators during the follow-up period.Conclusions:At baseline, several PFAS were cross-sectionally associated with small differences in markers of insulin secretion and β-cell function. However, there was limited evidence suggesting that PFAS concentrations are associated with diabetes incidence or changes in glycemic indicators during the follow-up period. https://doi.org/10.1289/EHP1612

Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review

“…This relationship between PFNA and diabetes was confirmed in a later cross-sectional study [ 6 ]. However, in two prospective studies, PFNA and other PFASs were observed to have no effect or even a protective effect [ 7 , 8 ].…”

“…Other cross-sectional studies have linked levels of PCBs and, especially, organochlorine pesticides to insulin sensitivity [ 20 ]. Although some phthalates and PFASs have been linked to impaired insulin sensitivity in humans, some studies have failed to reproduce the link between PFASs and insulin resistance [ 6 , 7 , 21 , 30 ].…”

Mitochondria as target of endocrine-disrupting chemicals: implications for type 2 diabetes

“…Among them, those with the most conclusive evidence of a diabetogenic role are plasticizers like BPA and phthalates, some persistent organic pollutants (POPs), such as dioxins, polychlorinated biphenyls (PCBs), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), and dichlorodiphenyltrichloroethane (DDT), as well as some heavy metals, including arsenic and cadmium (Gore et al 2015, Cardenas et al 2017.…”

Serum Levels of Perfluoroalkyl Substances (PFAS) in Adolescents and Young Adults Exposed to Contaminated Drinking Water in the Veneto Region, Italy: A Cross-Sectional Study Based on a Health Surveillance Program

“…PFOA and PFOS have endocrine-disruption properties and have been associated with several health conditions (EFSA CONTAM Panel 2018), including increased levels of serum cholesterol (Frisbee et al 2010;Winquist and Steenland 2014a), impaired thyroid function (Lopez-Espinosa et al 2012;Winquist and Steenland 2014b;Ballesteros et al 2017), insulin resistance (Cardenas et al 2017), gestational diabetes (Zhang C et al 2015), and pregnancy-induced hypertension (Darrow et al 2013).…”