Unacylated, acylated ghrelin and obestatin levels are differently inhibited by oral glucose load in pediatric obesity: Association with insulin sensitivity and metabolic alterations.

Background & Aims: Ghrelin levels are associated with insulin resistance, obesity and clustered abnormalities of the metabolic syndrome. Nutrients, mainly carbohydrates, influence ghrelin secretion. Obestatin is derived from the same precursor as ghrelin. Contemporary regulation of the three peptides, with respect to insulin sensitivity and metabolic syndrome, remains undefined in childhood and adolescence. Methods: A cross-sectional study in a tertiary care center. Acylated, unacylated ghrelin, obestatin, glucose and insulin were measured at fasting and post oral glucose load in 60 pediatric obese and 22 normal weight subjects classified with respect to those alterations that cluster in metabolic syndrome. Results: Acylated ghrelin decreased at 60 min and subsequently returned to basal levels (p < 0.001). Unacylated ghrelin and obestatin decreased for the entire test with a maximum inhibition at 60 and 120 min (p < 0.0001), respectively. Unacylated ghrelin inhibition was influenced by insulin sensitivity. The insulinogenic index was associated with the acylated ghrelin rebound (p < 0.002) and obestatin nadir (p < 0.006). Fasting unacylated ghrelin was reduced in metabolic syndrome due to insulin resistance. Obestatin variation was blunted in individuals who had alterations of the metabolic syndrome cluster (p < 0.0001), being predicted by lower HDL cholesterol and higher blood pressure. Conclusions: Acylated, unacylated ghrelin and obestatin present different dynamics after glucose load in pediatric individuals. Compensatory insulin secretion to insulin resistance and insulin sensitivity are the major contributors associated with the regulation of ghrelin as well as metabolic alterations with obestatin.