ESPE Abstracts

Background: due to its recently documented role in intercellular tight junction disassembly, zonulin has emerged as a valuable biological marker to assess the integrity of the intestinal mucosal barrier. Experimental studies have shown an association between intestinal permeability and obesity.

Objectives: aim of this study was to investigate the relationship between serum zonulin levels, both at baseline and postprandial, with body mass index (BMI) and biochemical markers of insulin resistance (IR), insulin sensitivity, β-cell function and cardio-metabolic risk in obese non-diabetic children and adolescents.

Methods: children and adolescents aged 5-16 years with BMI ≥ 2.0 SDS were recruited. Criteria of exclusion from the study were pre-term or post-term birth, genetic or endocrine causes of obesity, chronic diseases, or chronic pharmacological therapies. All the patients underwent complete clinical and biochemical assessment, including oral glucose tolerance test (OGTT) and liver ultrasonography (US). Zonulin serum levels were measured at fasting state, at 60-minute and 120-minute OGTT timepoint. Homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), Matsuda-index, Insulinogenic-index, areas under the curves for glucose and insulin were calculated. IR was defined as HOMA-IR >2.5 in prepubertal children and >4 in pubertal youths.

Results: 104 obese patients were enrolled (mean age 11.43 ± 2.66). Impaired fasting glucose was documented in 27.9% and impaired glucose tolerance in 12% of patients. 69.2% patients had insulin resistance. Liver steatosis was diagnosed in 39.4%. Zonulin serum levels significantly increased from baseline to 60-minute and 120-minute OGTT timepoint (P<0.001) in the entire study population. Variation in zonulin levels did not differ significantly from those of glucose and insulin curve. We found a positive correlation between BMI SDS and serum zonulin levels at 120-minute OGTT timepoint (P<0.05). Multiple linear regression model highlighted a positive association of Zonulin fasting levels with IR and glutamic-oxalacetic transaminase levels (P<0.05). No significant differences in zonulin levels were demonstrated for age, sex, pubertal status, glucose, lipid profile and the other obesity-related parameters.

Conclusions: Our results show, for the first time in a pediatric cohort, the meal-related pattern of secretion of serum zonulin, which tends to significantly increase during and at 2-hours postprandial assessment. Even if the underlying mechanisms associating intestinal permeability and obesity have not been fully elucidated yet, our data confirm a close relationship between zonulin concentration and obesity in pediatric population. IR seems to significantly influence zonulin serum levels, thus a central role of IR in this pathway is conceivable.