Hyperghrelinemia Precedes Obesity in Prader-Willi Syndrome

Abstract

BACKGROUND: 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. OBJECTIVE: The objective of the study was to investigate total plasma ghrelin levels in children with PWS and controls from 2 months to 17 years. SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.