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

By Sun, Qi; Cornelis, Marilyn C. et al. | Environmental Health Perspectives, June 2014 | Go to article overview

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


Sun, Qi, Cornelis, Marilyn C., Townsend, Mary K., Tobias, Deirdre K., Eliassen, A. Heather, Franke, Adrian A., Hauser, Russ, Hu, Frank B., Environmental Health Perspectives


Introduction

Extensive research has established the role of lifestyle, diet, and genetic variations in the etiology of type 2 diabetes (T2D) (Qi et al. 2008). Meanwhile, emerging evidence has led to a novel hypothesis that some of these chemicals, such as bisphenol A (BPA) and phthalates, may also be related to the rising epidemics of obesity and T2D (Casals-Casas and Desvergne 2011). Both classes of chemicals are produced in large quantities worldwide and have wide industrial applications (Casals-Casas and Desvergne 2011; Hauser and Calafat 2005) and can be detected ubiquitously in human urines (Calafat et al. 2008; Silva et al. 2004).

Animal experiments suggest that, in addition to its well-known estrogenic effects, BPA may also interfere with multiple pathways related to T2D, including impaired beta-cell function (Alonso-Magdalena et al. 2006), liver dysfunction (Bindhumol et al. 2003; Nakagawa and Tayama 2000), dysregulation of glucose metabolism and adiponectin release in adipocytes (Ben-Jonathan et al. 2009; Hugo et al. 2008), and disruption of thyroid hormone functions (Moriyama et al. 2002). Experimental evidence suggests that phthalates may also affect the liver and interfere with adipocyte biology and glucose metabolism through effects on peroxisome proliferator-activated receptors (PPARs) (Desvergne et al. 2009). Despite the accumulation of evidence from animal studies, evidence among humans for associations of BPA and phthalates with T2D has been limited to cross-sectional studies, with mixed findings (James-Todd et al. 2012; LaKind et al. 2012; Lang et al. 2008; Lind et al. 2012b; Ning et al. 2011; Shankar and Teppala 2011; Silver et al. 2011; Svensson et al. 2011).

Therefore, we analyzed data from two prospective cohort studies among U.S. women, the Nurses' Health Study (NHS) and the NHSII, to evaluate associations between urinary concentrations of BPA and phthalate metabolites and incident T2D. The non-overlapping age distributions between the two cohorts allowed us to examine these associations among different age groups and by menopausal status. Based on experimental data suggesting that BPA interferes with beta-cell functions by activating estrogen receptors (Alonso-Magdalena et al. 2006; Nadal et al. 2009; Soriano et al. 2012), we hypothesized that associations with BPA would be stronger in premenopausal women than in postmenopausal women.

Methods

Study population. The NHS was established in 1976 when 121,700 female registered nurses 30-55 years of age were enrolled, whereas in 1989 the younger counterpart NHSII cohort was initiated among a total of 116,430 female registered nurses 25-42 years of age. A total of 18,743 NHS participants 53-79 years of age provided blood and urine samples in 2000-2002. In 1996-2001, blood and urine samples were collected from 29,611 NHSII participants 32-52 years of age. Urine samples were collected without preservative in a polypropylene container and returned to a central biorepository via overnight courier with an icepack, where they were processed immediately upon arrival and aliquoted into polypropylene cryovials, which were stored in the vapor phase of liquid nitrogen freezers at [less than or equal to] -130[degrees]C. In both cohorts, a high follow-up rate of > 90% was maintained among participants who provided urine samples.

Assessment of covariates. NHS participants responded to a questionnaire inquiring about body weight, height, demographic and lifestyle information, and medical history at study baseline. Similar follow-up questionnaires have been administered biennially since baseline to update these variables. In 1984, 1986, and every 4 years thereafter, a validated food frequency questionnaire (FFQ) has been used to assess participants' usual diet. In the NHSII, questionnaires similar to those used in the NHS are sent biennially to update lifestyle and health-related characteristics. The FFQ was first administered in 1991 and is updated every 4 years in the NHSII. …

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