Suppression of Acylated Ghrelin during Oral Glucose Tolerance Test Is Correlated with Whole-Body Insulin Sensitivity in Children with Prader-Willi Syndrome

Abstract

Decreased fasting ghrelin levels and decreased ghrelin suppression in overweight children have been reported to be associated with insulin resistance. However, Prader-Willi syndrome (PWS) is associated with increased total ghrelin levels and relative hypoinsulinemia. The objective of the study was to analyze changes in acylated ghrelin (AG) and des-acylated ghrelin (DAG) levels after glucose loading and characterize correlations between insulin sensitivity and ghrelin suppression. Plasma glucose, insulin, AG, and DAG levels were measured in PWS children (n = 11) and normal obese controls (n = 10) during oral glucose tolerance testing. All subjects were admitted to the Samsung Medical Center. Oral glucose tolerance testing was performed in all subjects after an overnight fast. Plasma levels of the hormones AG, DAG, and insulin, and those of glucose at 0, 30, 60, 90, and 120 min after glucose challenge were measured, and whole-body insulin sensitivity index (WBISI) values were calculated. AG levels fell markedly more from fasting levels in PWS children than normal healthy obese controls at 30, 60, and 90 min after glucose challenge, but no significant differences in DAG levels were observed at any time between PWS patients and controls. Fasting AG and DAG levels were found to correlate with WBISI in PWS, and absolute suppressions (Delta from baseline) in AG at 30 min after glucose challenge (nadir) were also correlated with WBISI in PWS (r = 0.64, P = 0.035). Our results suggest that AG is sensitively suppressed by insulin and that this suppression correlated with insulin sensitivity in PWS children.