Association of Urinary Concentrations of Bisphenol A and Phthalate Metabolites with Risk of Type 2 Diabetes: A Prospective Investigation in the Nurses’ Health Study (NHS) and NHSII Cohorts

BACKGROUND: Prospective evidence regarding associations for exposures to bisphenol A (BPA) and phthalates with type 2 diabetes (T2D) is lacking. OBJECTIVE: We prospectively examined urinary concentrations of BPA and phthalate metabolites with T2D risk. METHODS: We measured BPA and eight major phthalate metabolites among 971 incident T2D case-control pairs from the Nurses' Health Study (NHS) (mean age, 65.6 years) and NHSII (mean age, 45.6 years). RESULTS: In the NHSII, BPA levels were not associated with incident T2D in multivariate-adjusted analysis until body mass index was adjusted: odds ratio (OR) comparing extreme BPA quartiles increased from 1.40 (95% CI: 0.91, 2.15) to 2.08 (95% CI: 1.17, 3.69; p(trend) = 0.02) with such an adjustment. In contrast, BPA concentrations were not associated with T2D in the NHS (OR = 0.81; 95% CI: 0.48, 1.38; p(trend) = 0.45). Likewise, urinary concentrations of total phthalate metabolites were associated with T2D in the NHSII (OR comparing extreme quartiles = 2.14; 95% CI: 1.19, 3.85; p(trend) = 0.02), but not in the NHS (OR = 0.87; 95% CI: 0.49, 1.53; p(trend) = 0.29). Summed metabolites of butyl phthalates or di-(2-ethylhexyl) phthalates were significantly associated with T2D only in the NHSII; ORs comparing extreme quartiles were 3.16 (95% CI: 1.68, 5.95; p(trend) = 0.0002) and 1.91 (95% CI: 1.04, 3.49; p(trend) = 0.20), respectively. CONCLUSIONS: These results suggest that BPA and phthalate exposures may be associated with the risk of T2D among middle-aged, but not older, women. The divergent findings between the two cohorts might be explained by menopausal status or simply by chance. Clearly, these results need to be interpreted with caution and should be replicated in future studies, ideally with multiple urine samples collected prospectively to improve the measurement of these exposures with short half-lives.