Hyperghrelinemia Precedes Obesity in Prader-Willi Syndrome

Abstract

High plasma ghrelin levels have been reported in Prader-Willi syndrome (PWS). However, little is known about plasma ghrelin in these children during the first years of life characterized by a failure to thrive. The objective of the study was to investigate total plasma ghrelin levels in children with PWS and controls from 2 months to 17 years. Forty children with PWS [24 boys, 16 girls, median age 3.6 yr, median body mass index (BMI) Z-score 0.3] were compared with 84 controls (57 boys, 27 girls, median age 4.2 yr median BMI Z-score 0.1). Children were then divided into two groups according to age and GH treatment. Median plasma ghrelin levels were significantly higher in children with PWS, compared with controls at any age (568 vs. 173, P < 0.0001) and decreased with age in both groups (P < 0.0001). In the whole group of PWS, we found an inverse relationship between ghrelin and BMI Z-score, insulin, homeostasis model assessment insulin resistance index, leptin, and lean mass. Plasma ghrelin levels were higher in children with PWS than controls, both in the youngest children below 3 yr who were not receiving GH (771 vs. 233, P < 0.0001) and in the children older than 3 yr, all of whom were treated with GH (428 vs. 159, P < 0.0001). Plasma ghrelin levels in children with PWS are elevated at any age, including during the first years of life, thus preceding the development of obesity.