Exposure to Phenols and Incident Diabetes in Midlife Women: The Study of Women's Health Across the Nation (SWAN)

Abstract

Background: Although environmental phenols have been suggested to be diabetogenic chemicals, few epidemiologic studies have investigated associations between phenols (except bisphenol-A [BPA]) and diabetes. Furthermore, most previous studies have been cross-sectional, raising concerns related to reverse causality. Objective: We examined the associations between urinary concentrations of phenols, assessed at two time points, and incident diabetes in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-ethnic prospective cohort of midlife women. Methods: We analyzed data of 1315 white, black, Chinese, and Japanese women aged 45-56 years who were diabetes-free at the baseline of the SWAN Multi-Pollutant Study (MPS) (1999–2000) and were followed up over 17 years. Twelve phenols (BPA, bisphenol-S, bisphenol-F, triclosan, triclocarban, 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, ethylparaben, methylparaben, butylparaben, propylparaben) were measured in urine samples collected at baseline and three years after the baseline (2002–2003). We generated inverse probability weights (IPW) to account for potential selection bias into the MPS and selective attrition during follow-up. The association of phenol to incident diabetes was examined using time-varying Cox proportional hazards models with IPW adjusted for potential confounders. Results: During follow-up (median =16 years), 184 incident cases were identified (incidence rate=9.96 per 1000 person-years (95% CI: 8.60,11.49). Compared with the first quartile, hazard ratios (HRs)for the second, third, and fourth quartiles of BPA were 2.86 (95% CI: 1.66, 4.94), 1.82 (0.97, 3.42), and 2.48 (1.39, 4.42). Conversely, HRs comparing the third and fourth quartiles of benzophenone-3 with the first quartile were 0.43 (0.27, 0.70) and 0.43 (0.26, 0.72). There were no statistically significant associations between other chemicals and incident diabetes. Conclusions: This prospective cohort study of midlife women suggests that BPA exposure may be associated with a higher risk of diabetes, while benzophenone-3 exposure may be associated with a lower risk.