Urine Levels of Phthalate Metabolites and Bisphenol A in Relation to Main Metabolic Syndrome Components: Dyslipidemia, Hypertension and Type 2 Diabetes. A pilot study

Abstract

SUMMARYAim: Human exposure to organic pollutants (some of them also called endocrine disruptors) can be associated with adverse metabolic health outcomes including type 2 diabetes. The aim of this study was to compare the urine levels of bisphenol A and phthalate metabolites in subgroups of patients with metabolic syndrome composed of patients with and without three important components of metabolic syndrome (hypertension, dyslipidemia and diabetes).Methods: We have investigated 24 hours urine samples of 168 patients with metabolic syndrome from the Metabolic Outpatient Department of General University Hospital in Prague. Using standard metabolic syndrome criteria, we classified patients as dyslipidemic (n = 87), hypertensive (n = 96), and type 2 diabetic (n = 58). Bisphenol A and 15 metabolites of phthalates were evaluated in relation to creatinine excretion. Samples were analysed with enzymatic cleavage of glucuronide using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in one laboratory with external quality control.Results: Four metabolites, mono-n-butyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-carboxypentyl) phthalate showed significantly higher levels in diabetic compared to non-diabetic patients (p < 0.001, p = 0.002, p = 0.002, and p = 0.005, respectively). The differences remained significant after adjustment to hypertension, dyslipidemia, age, and BMI. No difference was found between either the hypertensive and non-hypertensive or dyslipidemic and non-dyslipidemic patients. There was no significant relation of bisphenol A level to diabetes, hypertension, dyslipidemia, age, and BMI.Conclusions: Urine levels of four phthalate metabolites were significantly higher in type 2 diabetics independently on specified predictors. Phthalate levels can be in relation to beta cell dysfunction in type 2 diabetic patients but this study was not able to show if the relation is causal.

Association between Heavy Metals, Bisphenol A, Volatile Organic Compounds and Phthalates and Metabolic Syndrome

“…One review article [50] found that BPA increases insulin resistance with the consequent risk of diabetes. However, another study [19] directly examined the relationship between type 2 diabetes and BPA and showed similar results (not significant). Hence, the relationship between BPA and MetS must be investigated further.…”

“…Consequently, phthalate metabolites are detected in urine samples ubiquitously. Some studies [19,28,29] analyzed the association between phthalates metabolites and MetS. In a previous study conducted among a small number of adolescents (data from 918 people), a significant association was found between MnBP and MetS [28].…”

“…Other studies suggested the association between blood mercury concentration and MetS [17,18]. In the case of bisphenol A (BPA), a few studies [19,20] have reported that there is no association between urine BPA levels and diabetes, while other studies [21,22,23] showed different results. Many studies have reported the relationship between BPA and MetS (or MetS components; diabetes), but the results were inconsistent.…”

Plasticizers and Cardiovascular Health: Role of Adipose Tissue Dysfunction

“…Gaston and Tulve performed a cross-sectional study with NHANES data from 2003 to 2013 in U.S. adolescents (n 918) and discovered a strong association between MnBP and MetS (Gaston and Tulve, 2019). A smaller study examining MetS patients in a hospital in Prague (n 168) revealed significantly higher urine levels of four phthalate metabolites (MnBP, MEHHP, MEOHP, MECPP) in T2D patients compared to non-diabetic patients, but no relationship with hypertension or dyslipidemia (Piecha et al, 2016). Similarly, another study noted significantly elevated concentrations of DEHP and MECPP in T2D Mexican women; however, correlations between DEHP and IR were only noted for non-diabetic patients (Svensson et al, 2011).…”

Racial and Sex Differences between Urinary Phthalates and Metabolic Syndrome among U.S. Adults: NHANES 2005–2014

“…Phthalates are classified as xenoestrogens and have been negatively associated with several health conditions [ 11 ], including metabolic disorders such as obesity and insulin resistance [ 12 , 13 , 14 , 15 ]. The association between phthalate exposure and dyslipidemia is inconsistent, with two studies reporting either positive [ 16 ] or null associations [ 17 ]. These disorders contribute to metabolic syndrome (MetS), defined as having at least three of the five following criteria: elevated abdominal obesity, elevated triglycerides, high blood pressure, elevated fasting glucose levels, and reduced high-density lipoprotein (HDL) levels [ 18 ].…”