Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women

BACKGROUND: Emerging evidence suggests that perfluoroalkyl substances (PFASs) are endocrine disruptors and may contribute to the etiology of type 2 diabetes (T2D), but this hypothesis needs to be clarified in prospective human studies. OBJECTIVES: Our objective was to examine the associations between PFAS exposures and subsequent incidence of T2D in the Nurses’ Health Study II (NHSII). In addition, we aimed to evaluate potential demographic and lifestyle determinants of plasma PFAS concentrations. METHODS: A prospective nested case–control study of T2D was conducted among participants who were free of diabetes, cardiovascular disease, and cancer in 1995–2000 [([Formula: see text]): [Formula: see text]) of age]. We identified and ascertained 793 incident T2D cases through 2011 ([Formula: see text]) years of follow-up: [Formula: see text]). Each case was individually matched to a control (on age, month and fasting status at sample collection, and menopausal status and hormone replacement therapy). Plasma concentrations of five major PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonate, perfluorononanoic acid, and perfluorodecanoic acid were measured. Odds ratios (ORs) of T2D by PFAS tertiles were estimated by conditional logistic regression. RESULTS: Shorter breastfeeding duration and higher intake of certain foods, such as seafood and popcorn, were significantly associated with higher plasma concentrations of PFASs among controls. After multivariate adjustment for T2D risk factors, including body mass index, family history, physical activity, and other covariates, higher plasma concentrations of PFOS and PFOA were associated with an elevated risk of T2D. Comparing extreme tertiles of PFOS or PFOA, ORs were 1.62 (95% CI: 1.09, 2.41; [Formula: see text]) and 1.54 (95% CI: 1.04, 2.28; [Formula: see text]), respectively. Other PFASs were not clearly associated with T2D risk. CONCLUSIONS: Background exposures to PFASs in the late 1990s were associated with higher T2D risk during the following years in a prospective case–control study of women from the NHSII. These findings support a potential diabetogenic effect of PFAS exposures. https://doi.org/10.1289/EHP2619