Urinary Phthalate Metabolite Concentrations and Diabetes Among Women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008

Tamarra James-Todd; Richard Stahlhut; John D. Meeker; Sheena-Gail Powell; Russ Hauser; Tianyi Huang; Janet Rich-Edwards

Disclosures

Environ Health Perspect. 2012;120(9):1307-1313. 

In This Article

Abstract and Introduction

Abstract

Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women.
Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study.
Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79years of age who participated in the NHANES (2001–2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment–estimated insulin resistance, and glycosylated hemoglobin A1c.
Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR= 1.96 (95% CI: 1.11, 3.47) and OR= 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance.
Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

Introduction

Among women, the prevalence of diagnosed diabetes doubled from 1980 to 2010, with the age-adjusted prevalence increasing from 2.9% to 5.9% [Centers for Disease Control and Prevention (CDC) 2011a]. Although increased body mass index (BMI) is a major risk factor of diabetes (Colditz et al. 1995; Flegal et al. 2010; Mokdad et al. 2000), other factors are thought to be involved in the type 2 diabetes (T2DM) epidemic (Stahlhut et al. 2007; Svensson et al. 2011; Thayer et al 2012). In particular, certain types of environmental endocrine-disrupting chemicals (EDCs) have been implicated as having the ability to alter both adiposity and insulin resistance (Hatch et al. 2008; Latini et al. 2009; Newbold 2010; Stahlhut et al. 2007). Phthalates may be among those EDCs with the joint ability to impact adipogenesis and dysregulate glucose metabolism (Casals-Casas et al. 2008; Desvergne et al. 2009; Grun and Blumberg 2007).

Phthalates are a class of chemicals used in the manufacturing of a variety of products (Crinnion 2010; Hauser and Calafat 2005; Romero-Franco et al. 2011). These chemicals are often used as plasticizers or solvents in food packaging, cosmetics, perfumes, nail polishes, flooring, and other industrial products. For the past 50 years, phthalate production has increased (Baillie-Hamilton 2002). Phthalate exposure is nearly ubiquitous, with > 75% of the U.S. population having detectable urine concentrations of many phthalate metabolites (Hauser and Calafat 2005).

Recent studies have suggested that phthalates may disrupt metabolism and adipogenesis (Casals-Casas et al. 2008; Desvergne et al. 2009; Grun and Blumberg 2007). Specifically, phthalates can bind to peroxisome proliferator-activated receptors (PPAR) alpha and gamma, which regulate glucose metabolism and adipogenesis, respectively (Casals-Casas et al. 2008; Desvergne et al. 2009; Grun and Blumberg 2007). Dysregulation of glucose metabolism, possibly through increased insulin resistance, is a hallmark of T2DM.

In a cross-sectional study of a representative sample of U.S. men participating in NHANES, Stahlhut et al. (2007) showed that exposure to higher levels of phthalates was associated with increased waist circumference and insulin resistance—both risk factors for T2DM. In a cross-sectional study of Mexican women, Svensson et al. (2011) found that higher exposure of certain phthalates was associated with T2DM. Although the prevalence of diabetes is similar among men and women in the United States, differences in fat storage and hormonal profiles related to insulin resistance exist (Tsatsoulis et al. 2009). If certain environmental chemicals have the ability to alter adiposity and insulin resistance, then exposure to these chemicals could vary by sex. Women may be particularly vulnerable to metabolic disruption of phthalates, given their higher concentrations of certain urinary phthalate metabolites (Silva et al. 2004).

In this study, we analyzed data from women 20–79 years of age who participated in the National Health and Nutrition Examination Survey 2001–2008 (NHANES). We estimated the association of diabetes with concentrations of monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and the sum of three di(2-ethylhexyl) phthalate (DEHP) metabolites [mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)]. To estimate the association between these phthalates and diabetes, we adjusted for sociodemographic characteristics and behavioral factors. Because diet is one of the main sources of exposure for certain phthalates, we adjusted for dietary factors, including total caloric and fat intake (Grun and Blumberg 2007; Hauser and Calafat 2005). We also adjusted for BMI and waist circumference, which could not be ruled out as potential intermediates or confounders given the cross-sectional study design. To determine whether phthalate exposure was associated with factors that likely precede the onset of diabetes, we conducted a secondary analysis to estimate associations between phthalate metabolites and fasting blood glucose (FBG), homeostasis model assessment–estimated insulin resistance (HOMA-IR), and glycosylated hemoglobin A1c (A1c) among women who did not have a diagnosis of diabetes. We hypothesized that higher urinary phthalate levels would be associated with an increased odds of prevalent diabetes.

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