Phthalates and Incident Diabetes in Midlife Women: The Study of Women’s Health Across the Nation (SWAN)

Abstract

Context: Phthalates are hypothesized to contribute to diabetes, but longitudinal evidence in humans is limited. Objective: We examined whether phthalate exposure was associated with a higher incidence of diabetes in a racially/ethnically diverse cohort of midlife women. Methods: In the Study of Women’s Health Across the Nation Multipollutant Study, we followed 1308 women without diabetes in 1999-2000 for 6 years. Eleven phthalate metabolites were measured in spot urine samples in 1999-2000 and 2002-2003. Incident diabetes was ascertained between 1999-2000 and 2005-2006. Cox proportional hazards models with time-varying exposure were used to estimate the hazard ratio (HR) of diabetes associated with each phthalate metabolite, adjusting for demographic, lifestyle, and health-related factors. Effect modification by race/ethnicity was examined with interaction terms. Results: Sixty-one women developed diabetes over 6 years (cumulative incidence = 4.7%). Among all women, several high-molecular-weight phthalate metabolites were associated with a higher incidence of diabetes, but none were statistically significant. There was effect modification by race/ethnicity. Among White women, each doubling of the concentrations of mono-isobutyl phthalate (MiBP), monobenzyl phthalate, mono-carboxyoctyl phthalate, mono-carboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate was associated with a 30% to 63% higher incidence of diabetes (HR = 1.30, 95% CI, 1.03-1.65 for MCNP; HR = 1.63, 95% CI, 1.18-2.25 for MiBP). In contrast, phthalates were not associated with diabetes incidence in Black or Asian women. Conclusions: Some phthalate metabolites were associated with a higher incidence of diabetes over 6 years, but the associations were inconsistent across racial/ethnic groups. Whether phthalates cause diabetes requires further investigation.