Nonlinear associations between dietary exposures to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and type 2 diabetes risk in women: Findings from the E3N cohort study

The incidence of type 2 diabetes (T2D) is steadily rising worldwide since the past 30 years. There is increasing interest in understanding the contribution of exposure to endocrine disrupting chemicals (EDCs) to T2D trend. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are stable, persistent, and bioaccumulative synthetic compounds, suspected to act as EDCs and for which the diet is the main route of exposure. We investigated associations between estimated dietary exposure to PFOS and PFOA and the risk of T2D in the large E3N prospective cohort study.Among 71 270 women included in this study, 2680 cases of incident type 2 diabetes were validated during follow-up (1993–2012). Dietary exposure was estimated combining dietary consumption data collected in E3N and food contamination data provided by ANSES in the 2nd French Total Diet Study. The estimated mean dietary exposure to PFOS and PFOA was 0.50?ng/kg _{body weight}/day and 0.86?ng/kg _{body weight}/day respectively. An inverse U-shape association was found when considering PFOA and T2D: women in the 4th, 5th, and 6th decile groups had a HR [95%CI] of 1.21 [1.06–1.46], 1.35 [1.15–1.59], and 1.33 [1.05–1.41], respectively, when compared to women of the 1st decile group, while the other decile groups were not associated to the risk of T2D. The positive association had the strongest effect size for non-obese women (body mass index (BMI) ≤25?kg/m²). No association was found between dietary exposure to PFOS and T2D, except when considering only women with BMI≤25?kg/m2, in which a positive nonlinear association was observed (HR [95%CI]?=?1.46 [1.09–1.96], 1.52 [1.09–2.11], and 1.44 [1.01–2.06] for the 6th, 8th, and 9th decile groups respectively).This is the first study to evaluate the association between dietary exposure to PFOA and PFOS and the risk of developing T2D in a large observational study with over 15 years of follow-up. The present study highlights the importance of studying the effects of EDCs in large epidemiological studies including not occupationally exposed populations, as well as the importance of considering exposure to PFOS and PFOA as a relevant risk factor for T2D.