The effect of growth hormone on the response of total and acylated ghrelin to a standardized oral glucose load and insulin resistance in children with Prader-Willi syndrome.
BACKGROUND
Fasting levels of plasma ghrelins are grossly elevated in children with Prader-Willi syndrome (PWS). The cause of this elevation and the regulation of ghrelins in PWS is largely unknown. The regulatory role of individual nutritional components and of GH is not well characterized.


OBJECTIVE
We investigated the influence of GH on acylated (aGhr) and total ghrelin (tGhr) concentrations before and after an oral glucose load, and on insulin resistance in PWS children.


METHODS
In a clinical follow-up study, plasma ghrelins were measured during an oral glucose tolerance test, and parameters of insulin resistance were determined in 28 PWS children before and/or 1.18 (0.42-9.6) yr (median, range) after start of GH therapy (0.035 mg/kg body weight per day).


METHODS
Fasting and postglucose concentrations of aGhr and tGhr and homeostasis model assessment 2 insulin resistance were the main outcome measures.


METHODS
The study was conducted in a single center (University Children's Hospital).


RESULTS
High fasting [1060 +/- 292 (sd) pg/ml; n = 12] and postglucose trough (801 +/- 303 pg/ml; n = 10) tGhr concentrations in GH-untreated PWS children were found to be decreased in the GH-treated group (fasting 761 +/- 247 pg/ml, n = 24, P = 0.006; postglucose 500 +/- 176 pg/ml, n = 20; P = 0.006). In contrast, aGhr concentrations and insulin resistance were not changed by GH treatment. Both aGhr and tGhr concentrations were decreased by oral carbohydrate administration, independent of the GH treatment status.


CONCLUSIONS
Our results indicate that, in PWS children, aGhr and tGhr are differentially regulated by GH.
Hauffa
Berthold P
BP
Department of Pediatric Hematology/Oncology and Endocrinology, University Children's Hospital, Hufelandstrasse 55, D-45122 Essen, Germany. berthold.hauffa@uni-essen.de
Haase
Katja
K
Range
Ina M
IM
Unger
Nicole
N
Mann
Klaus
K
Petersenn
Stephan
S
D000215:Acylation; D000293:Adolescent; D001786:Blood Glucose / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D054439:Ghrelin; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D036361:Peptide Hormones / Q000097:blood* / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000097:blood* / Q000188:drug therapy*
D001786:Blood Glucose; D054439:Ghrelin; D036361:Peptide Hormones; D013006:Growth Hormone