Delayed Response of Amylin Levels after an Oral Glucose Challenge in Children with Prader-Willi Syndrome

Abstract

PurposeAmylin secretion is increased parallel to insulin in obese subjects. Despite their marked obesity, a state of relative hypoinsulinemia occurs in children with Prader-Willi syndrome (PWS). Based on the hypothesis that amylin levels may be relatively low in PWS children, contributing to their excessive appetite, we studied amylin levels after oral glucose loading in children with PWS and overweight controls.Materials and MethodsPlasma levels of amylin, glucagon, insulin, and glucose were measured at 0, 30, 60, 90, and 120 min after a glucose challenge in children with PWS (n = 18) and overweight controls (n = 25); the relationships among the variables were investigated in these two groups.ResultsAmylin levels were significantly correlated with insulin during fasting and during the oral glucose tolerance test in both groups. Amylin levels between 0 and 60 min after glucose loading were statistically different between the two groups. They were lower in children with PWS than in the controls between 0 and 30 min after glucose loading.ConclusionThe relatively low levels of amylin, compared to those in overweight controls, during the early phase of glucose loading in patients with PWS, may contribute, in part, to the excessive appetite of PWS patients as compared to the overweight controls.

Amylin: Pharmacology, Physiology, and Clinical Potential

“…Amylin Secretion in the Obese State. Although regulation of amylin secretion has not been extensively evaluated in humans, there is some evidence for elevation of amylin in the obese state (Ludvik et al, 1991;Enoki et al, 1992;Hanabusa et al, 1992; Amylin Blackard et al, 1994;Kautzky-Willer et al, 1994;Roth et al, 2010;Lee et al, 2011;Jacobsen et al, 2012). Plasma levels appear to reach up to approximately twice those achieved in nonobese subjects, but whether this results overall in sustained levels of amylin in excess of those that would be achieved postprandially is not clear.…”

Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?

“…However, since the lack of BDNF postprandial peak was also shown in obese patients [ 22 ], BDNF postprandial peak in healthy subjects may have been masked by the lack of peak in obese (both in Cluster 1) and contributed to the absence of differences between clusters. There is only one study [ 20 ] evaluating amylin in children with PWS finding lower postprandial amylin concentrations which correlated with insulin concentrations. A relative hypoinsulinemia is described in PWS [ 16 , 17 , 44 ], and fasting insulin levels in PWS in the present study were in the same line, however, no differences between clusters were observed.…”

“…Most studies also agree finding low concentrations of pancreatic polypeptide (PP) [ 7 , 8 , 9 ]. The results are controversial with regard to other hormones such as peptide YY (PYY) [ 10 , 11 , 12 , 13 , 14 , 15 ] or Glucagon-like peptide-1 (GLP-1) [ 16 , 17 , 18 , 19 ], and there are few studies exploring others such as glucose-dependent insulinotropic polypeptide (GIP) [ 8 , 15 ], amylin [ 20 ] or brain-derived neurotrophic factor (BDNF) [ 21 , 22 ].…”

Amylin and Calcitonin: Potential Therapeutic Strategies to Reduce Body Weight and Liver Fat

“…In clinical trials, circulating amylin levels seem to tightly correlate with fat mass. Studies indicate that basal and glucose or meal-stimulated levels of amylin are elevated in individuals with obesity (65)(66)(67)(68)(69)(70)(71)(72)(73)(74). This may relate to the role of amylin as a regulator of body mass but could also be a manifestation of the increased beta cell secretory activity often found in obesity.…”