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

J Clin Endocrinol Metab. 2019 May 1;104(5):1491-1499. 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.

Trial registration: ClinicalTrials.gov NCT03622957.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / chemically induced
  • Albuminuria / pathology*
  • Biomarkers / analysis
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Environmental Exposure / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney / drug effects
  • Kidney / physiopathology*
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Phthalic Acids / adverse effects*
  • Prognosis

Substances

  • Biomarkers
  • Phthalic Acids
  • phthalic acid

Associated data

  • ClinicalTrials.gov/NCT03622957