Projects / Metabolic disorders / DEHP metabolites

Relationships between urinary concentrations of DEHP metabolites, obesity and insulin sensitivity in obese children


In collaboration with:

Clinica Pediatrica e Dipartimento età evolutiva, University Hospital of Parma, Italy

Sergio Bernasconi, Maria Elisabeth  Street

Bracco Foundation, Milan, Italy

Enzo Grossi

Endocrine disorders are commonly related to improper functioning of the endocrine system. The hormone imbalance (or endocrine disease/condition) can affect human health inducing a lot of conditions such as diabetes mellitus, thyroid disease, and obesity. The detection in human fluid, such as urine, of metabolites of specific compounds, supposed to be endocrine disruptors, could be a valid method to explore the potential causes for endocrine disorders. Phthalates are used in a variety of consumer products; therefore they are considered ubiquitous contaminants. In particular di-(2-ethylhexyl) phthalate (DEHP) was the most used plasticizer. Therefore, we focused on the investigation of the presence of urinary concentrations of DEHP metabolites by HPLC-ESI-MS, in two populations of obese and autistic patients in comparison with healthy controls.

Metabolism of DEHP (Koch et al., Int J Androl, 2006, 29,155–165)

Data suggest that endocrine-disrupting chemicals, as phthalates, found in a variety of household products, may influence mechanisms related to obesity. Therefore, in this research project we focused on the evaluation of a possible association between urinary phthalate metabolites and age, gender, pubertal development, age at onset of obesity, indexes of insulin sensitivity, and metabolic syndrome in obese children. Urine concentrations of DEHP metabolites, are measured by HPLC-ESI-MS (HPLC electrospray ionization MS). The data were analyzed applying an innovative statistical methods based on Artificial Neural Networks (ANNs) and principal component analysis and connectivity Map. The results obtained supported the hypothesis that the higher metabolites in urine, the earlier the onset of obesity, and suggested that some DEHP metabolites are capable of influencing insulin sensitivity. However, the less phthalates were metabolized (higher MEHP urine concentrations) the later was the onset of obesity. It remains, thus, 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. This could explain also the positive relationship of MEHP with whole body insulin sensitivity index (WBISI).


 Correlations  Principal Component Analysis and Connectivity Map


Oral presentation

Relationships between urinary concentrations of PHTALOX, obesity and insulin sensitivity in obese children: a pilot study.  ME Street,  A.M Papini, C. Testa, F. Nuti, E. Grossi , S. Bernasconi .The Obese Species workshop, Erice Italy 21-26 October 2011




Di-(2-Ethylhexyl)Phthalate Metabolites in Urine Show Age-Related Changes and Associations with Adiposity and Parameters of Insulin Sensitivity in Childhood.

A. Smerieri, C. Testa, P. Lazzeroni, F. Nuti, E. Grossi, S. Cesari, L. Montanini, G. Latini, S. Bernasconi, A.M. Papini, and M.E. Street. PLoS ONE (2015) 10(2), 1-16: e0117831. Open Access Article.