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) [β_PFOS=0.39; 95% confidence interval (CI): 0.13, 0.66; β_PFOA=0.64; 95% CI: 0.34, 0.94], β-cell function (HOMA-β) (β_PFOS=9.62; 95% CI: 1.55, 17.70; β_PFOA=15.93; 95% CI: 6.78, 25.08), fasting proinsulin (β_PFOS=1.37 pM; 95% CI: 0.50, 2.25; β_PFOA=1.71 pM; 95% CI: 0.72, 2.71), and glycated hemoglobin (HbA_1c) (β_PFOS=0.03%; 95% CI: 0.002, 0.07; β_PFOA=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.

Figure 1.

Spearman correlation coefficients for plasma per- and polyfluoroalkyl substances (PFAS) concentrations measured at baseline in the Diabetes Prevention Program. Note: Et-PFOSA-AcOH, N-ethyl-perfluorooctane sulfonamido acetic acid; Me-PFOSA-AcOH, N-methyl-perfluorooctane sulfonamido acetic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctanesulfonic acid.

Figure 2.

Adjusted estimated change in glycemic outcomes per year for each doubling in per- and polyfluoroalkyl substances (PFAS) plasma concentrations measured at baseline in the Diabetes Prevention Program. Note: Longitudinal models adjusted for participant sex, race/ethnicity, baseline body mass index (BMI) (continuous), age (categorical), marital status (categorical), education (categorical), smoking history (categorical), time to follow-up in years, and treatment assignment (placebo/lifestyle). Et-PFOSA-AcOH, N-ethyl-perfluorooctane sulfonamido acetic acid; Me-PFOSA-AcOH, N-methyl-perfluorooctane sulfonamido acetic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctanesulfonic acid.

Figure 3.

Kaplan-Meier plot of diabetes-free incidence in the study sample by plasma concentrations of Sb-PFOA categorized as undetectable ($<\text{LOD}$) and detectable plasma Sb. PFOA concentrations ($\ge \text{LOD}$). Note: $\text{Limit}\text{of}\text{detection}\left(\text{LOD}\right)=0.1\text{ng}/\mathrm{mL}$. Sb-PFOA, sum of perfluoromethylheptanoic and perfluorodimethylhexanoic acids.