Phthalates Exposure as Determinant of Albuminuria in Subjects With Type 2 Diabetes: A Cross-Sectional Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 5; pp. 1491 - 1499
• Main Authors: Mengozzi, Alessandro, Carli, Fabrizia, Biancalana, Edoardo, Della Latta, Veronica, Seghieri, Marta, Gastaldelli, Amalia, Solini, Anna
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.05.2019; Copyright Oxford University Press; Oxford University Press
• Subjects: Aged; Albuminuria - chemically induced; Albuminuria - pathology; Biomarkers - analysis; Blood pressure; Body mass index; Creatinine; Cross-Sectional Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetics; Environmental Exposure - adverse effects; Epidemiology; Epidermal growth factor receptors; Esters; Female; Follow-Up Studies; Glomerular filtration rate; Humans; Insulin; Insulin resistance; Kidney - drug effects; Kidney - physiopathology; Kidney Function Tests; Male; Metabolites; Microvasculature; Middle Aged; Phenotypes; Phthalate esters; Phthalic Acids - adverse effects; Pollutants; Prognosis; Renal function; Type 2 diabetes
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-01797

Abstract Context Recent epidemiological observations have reported an association among phthalates exposure and insulin resistance, obesity, and diabetes but have not related exposure to these environmental pollutants with microvascular complications of diabetes. Objective To explore the relationship between phthalates and renal function in subjects with diabetes. Design Cross-sectional, case-only study. Concentrations of three urinary metabolites of di-2-ethylhexylphthalate were quantified in a spot morning urine sample, normalized for creatinine urinary excretion, and related to clinical parameters and phenotype, adjusting for confounders. Patients Two hundred and nine patients with diabetes consecutively referred to our clinic. Main Outcome Measures Relationship between phthalates and renal function [evaluated with estimated glomerular filtration rate (eGFR) and albuminuria]. Results Creatinine-adjusted urinary concentrations of mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-2-ethyl-5-hydroxyhexyl phthalate were 7.53 µg/g (range, 4.84 to 12.60), 3.04 µg/g (range, 1.03 to 5.14), and 10.70 µg/g (7.02 to 17.40), respectively. Age, sex, body mass index, diabetes duration, smoking, blood pressure, glycated Hb, and eGFR did not influence their levels. Exposure to MEHP and MEOHP was greater in individuals with microalbuminuria/macroalbuminuria (MEHP, P = 0.0173; MEOHP, P = 0.0306). The fourth vs first quartile showed a greater risk of albuminuria (MEHP: OR, 4.83; 95% CI, 1.45 to 16.06; P = 0.0297; MEOHP: OR, 3.29; 95% CI, 1.08 to 10.04); P = 0.0352). MEOHP was greater (P = 0.034) in subjects with cardiovascular events; MEHP showed a positive trend (P = 0.061). Conclusion Our findings have revealed an association between exposure to di-2-ethylhexylphthalate metabolites and the degree of albuminuria in subjects with diabetes; the lack of a relationship with eGFR suggests their urinary levels are independent of renal function. In this cross-sectional study of subjects with type 2 diabetes and various degrees of renal function, an association between phthalates (endocrine disruptors) and the risk of albuminuria emerged.