Marked suppression of ghrelin concentration by insulin in Prader-willi syndrome

Abstract

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.

Fig. 1

The mean insulin level during the insulin infusion (15 min to 120 min) in the control and PWS group was 92.09±6.36 mIU/mL and 81.48±3.21 mIU/mL, respectively, which was not statistically different.

Fig. 2

The plasma ghrelin level in the control and PWS groups over the 90 min period of insulin infusion was reduced from a basal value of 0.86±0.15 to 0.58±0.12 ng/mL and 2.38±0.76 to 1.12±0.29 ng/mL, respectively. The plasma ghrelin levels were relatively constant at these reduced levels until 15 min after the insulin infusion had been discontinued. The plasma ghrelin level was suppressed maximally at 90 min after insulin infusion. The plasma ghrelin levels in PWS patients were not suppressed to a level lower that of the control during the study period.

Fig. 3

The plasma ghrelin level was suppressed maximally at 90 min after insulin infusion by 26.81±4.66% in the controls and by 47.95±5.15% in the PWS group. The degree of ghrelin suppression was higher in the PWS group after the 90 min infusion of insulin infusion than in the control (p=0.011).

Fig. 4

The area under the curve (AUC) below the baseline was higher for the PWS group than in the control during the 90 min of insulin infusion (-92.82±44.4 vs. -10.41±2.87 ng/mL/ 90 min) (p=0.011) and during the entire insulin infusion period of 120 min (-130.17±59.51 vs. -16.54±4.04 ng/mL/120 min) (p=0.011).

Fig. 5

The mean glucose infusion rate at the steady state (90-120 min) in the PWS patients (5.93±0.93 mg/kg/min) was higher than in the controls (2.59±1.17 mg/kg/min), but this was not significant (p=0.088).