Per- and Polyfluoroalkyl Substances (PFAS) and Incident Diabetes in Midlife Women: Study of Women’s Health Across the Nation (SWAN)

Abstract

Background: Diabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on population-based prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women’s Health Across the Nation (SWAN), a community-based population study of midlife women.Methods: We included 1,226 diabetes-free women aged 45-56 years at the baseline of the SWAN Multi-Pollutant Study in 1999-2000 who were followed up to 2016. Serum PFAS concentrations were quantified by online solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry. We used k-means clustering and identified three overall PFAS concentration patterns as mixtures (low, medium, high). Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs).Results: We identified 137 incident diabetes cases (median follow-up=16 years, incident rate=8.15 per 1000 person-years). After adjustment for age, race/ethnicity, site, education, income, body mass index, smoking status, alcohol, physical activity, menopausal status and hormone use, the HRs comparing the lowest with the highest tertiles were 1.56 (95% CI: 1.15-2.11) for n-perfluorooctanoate (n-PFOA) (p-for-trend=0.004); 1.56 (95% CI: 1.19-2.14) for perfluorohexane sulfonate (PFHxS) (p-for-trend=0.001); 1.43 (95% CI: 1.05-1.95) for branched-perfluorooctane sulfonate (branched-PFOS) (p-for-trend=0.02); and 1.61 (95% CI: 1.16-2.24) for 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA) (p-for-trend=0.003). The high overall PFAS concentration mixture pattern had a significantly higher HR of 1.44 (95% CI: 1.01-2.05) compared with the low mixture pattern.Conclusions: This prospective cohort study with up to 17 years of follow-up suggests that PFAS, especially PFOA, PFHxS, and PFOS and its precursor (MeFOSAA), individually or as mixtures, may increase diabetes risk in midlife women. Reduced exposure to PFAS may be an important preventative approach to lowering population-wide diabetes risk.