Peptide YY, Cholecystokinin, Insulin and Ghrelin Response to Meal did not Change, but Mean Serum Levels of Insulin is Reduced in Children with Prader-Willi Syndrome

Abstract

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome

“…PYY Fasting PYY levels in PWS did decline with age (more steeply than in controls) and eating code in our study. However, we found overall normal fasting PYY levels in PWS children under 5 years compared with the controls, in agreement with other studies in children over 4 or 11 years 41,44 and adults. 38,43,59 One study has reported elevated fasting PYY levels in PWS children over 7 years.…”

“…While fasting or post-prandial insulin levels have sometimes been reported as low in human PWS children, 44,58 this has not been found in the current study and others. 28,39,41,45,48 In addition low fasting and postprandial insulin levels in PWS children and adults may be related more to preserved insulin sensitivity than reduced insulin secretion, as supported by reduced hypertriglyceridaemia and altered levels of related adipocytokines, such as increased plasma adiponectin in PWS. 23,24,29,30,34,38,45,48 Similar discrepancies have been seen for glucagon with fasting levels reported as low in one study of PWS children (410 years) and adults, 25 but normal fasting and post-prandial glucagon levels in another adult study.…”

“…38,43,59 One study has reported elevated fasting PYY levels in PWS children over 7 years. 45 Post-prandial PYY levels have generally been found to be normal in PWS children and adults, 38,41,44 though one study found decreased post-prandial levels. 43 Similarly fasting plasma levels of the anorexigenic gut hormone GLP-1 that is cosecreted from intestinal L-cells with PYY appear normal in PWS children and adults, 10,34,38,48 and post-prandial GLP-1 levels are normal in PWS adults PWS.…”

“…43 Similarly fasting plasma levels of the anorexigenic gut hormone GLP-1 that is cosecreted from intestinal L-cells with PYY appear normal in PWS children and adults, 10,34,38,48 and post-prandial GLP-1 levels are normal in PWS adults PWS. 10,38 Fasting and post-prandial plasma levels of CCK 11,23,25,41 and GIP, 21,38,45 other gut hormones involved in appetite regulation and glucose homeostasis, also appear normal in PWS children (over 7 --11 years) or adults. It therefore seems unlikely that deficiency of anorexigenic hormone PYY (or these other gut hormones) has a pathogenic role in hyperphagia in PWS.…”

In adults with Prader–Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels

“…Some have found that adults and children with PWS have lower fasting and postprandial PYY levels than controls (Butler et al, 2004 andGimenez-Palop et al, 2007), while others reported no difference (Goldstone et al, 2005 andPaik et al, 2007a) or increased PYY levels (Bizzarri et al, 2010).…”