Di-(2-ethylhexyl) phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood

PLoS One. 2015 Feb 23;10(2):e0117831. doi: 10.1371/journal.pone.0117831. eCollection 2015.

Abstract

Objectives: Phthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl) phthalate (DEHP) in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity.

Design and methods: DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP), were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables.

Results: The data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity.

Conclusion: It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / physiology*
  • Age Factors
  • Analysis of Variance
  • Body Mass Index
  • Body Size / physiology*
  • Child
  • Chromatography, Liquid / methods
  • Diethylhexyl Phthalate / analogs & derivatives
  • Diethylhexyl Phthalate / chemistry
  • Diethylhexyl Phthalate / metabolism
  • Diethylhexyl Phthalate / urine*
  • Female
  • Geography
  • Humans
  • Insulin Resistance / physiology*
  • Italy
  • Male
  • Mass Spectrometry / methods
  • Molecular Structure
  • Obesity / physiopathology
  • Obesity / urine
  • Puberty / physiology

Substances

  • Diethylhexyl Phthalate
  • mono-(2-ethylhexyl)phthalate

Grants and funding

This study was supported by funds of the Dept. of Paediatrics, University of Parma, Italy, by Bracco Foundation, Milan, Italy, by Fondazione Ente Cassa di Risparmio di Firenze (Italy), the Regione Toscana (Italy): POR CReO FESR 2007-2013 ASSE 1- Linea di intervento 1.1.C Bando Regionale 2009, the ANR(France) for the Chaire d’Excellence to AMP Project PepKit ANR-09-CEXC-013-01 and the Ecole Doctorale Sciences et Ingénierie de l’Université de Cergy-Pontoise for the PhD fellowship at CT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.