TY - JOUR
T1 - Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty
AU - Sørensen, Kaspar
AU - Aksglaede, Lise
AU - Munch-Andersen, Thor
AU - Aachmann-Andersen, Niels Jacob
AU - Leffers, Henrik
AU - Helge, Jørn Wulff
AU - Hilsted, Linda
AU - Juul, Anders
N1 - Keywords: Adolescent; Alleles; Child; Cross-Sectional Studies; Exons; Female; Gene Deletion; Glucose; Humans; Insulin; Insulin-Like Growth Factor I; Male; Polymorphism, Genetic; Puberty; Receptors, Somatotropin; Triglycerides
PY - 2009
Y1 - 2009
N2 - CONTEXT: The GH/IGF-I axis has major impact on insulin sensitivity and insulin secretion. Recently a polymorphism in the GH receptor gene (GHR), a genomic deletion of exon 3 (GHRd3), has been linked to increased responsiveness to GH. OBJECTIVE: The objective of the present study was to evaluate the impact of the GHRd3 gene polymorphism on insulin sensitivity, insulin secretion, lipids, and IGF-I levels in healthy children and adolescents. DESIGN: This was cross-sectional and was part of the COPENHAGEN puberty study. SETTING: The study was conducted at a tertiary center for pediatric endocrinology. PARTICIPANTS: Participants included 142 healthy Caucasian subjects (65 boys) aged 8.5-16.1 yr. Interventions: Standard 2-h oral glucose tolerance tests were preformed. GHR genotypes were determined by multiplex PCR. Main outcome measures were insulin sensitivity, insulin secretion, serum lipids, and IGF-I levels. RESULTS: Insulin secretion was higher in children and adolescents with a least one GHRd3 allele, even after adjustment for age, sex, pubertal stage, and insulin sensitivity (P = 0.018). Disposition index was higher in GHRd3-positive subjects (P = 0.026). In addition, the GHRd3 allele was associated with higher triglyceride (P = 0.028), but not IGF-I levels. CONCLUSION: The presence of at least one GHRd3 allele was associated with higher insulin secretion for a given degree of insulin sensitivity in healthy children and adolescents during puberty. In addition, the presence of the GHRd3 allele was associated with a higher disposition index. Thus, this common polymorphism in the GHR gene might play a role for pancreatic beta-cell compensatory capacity.
AB - CONTEXT: The GH/IGF-I axis has major impact on insulin sensitivity and insulin secretion. Recently a polymorphism in the GH receptor gene (GHR), a genomic deletion of exon 3 (GHRd3), has been linked to increased responsiveness to GH. OBJECTIVE: The objective of the present study was to evaluate the impact of the GHRd3 gene polymorphism on insulin sensitivity, insulin secretion, lipids, and IGF-I levels in healthy children and adolescents. DESIGN: This was cross-sectional and was part of the COPENHAGEN puberty study. SETTING: The study was conducted at a tertiary center for pediatric endocrinology. PARTICIPANTS: Participants included 142 healthy Caucasian subjects (65 boys) aged 8.5-16.1 yr. Interventions: Standard 2-h oral glucose tolerance tests were preformed. GHR genotypes were determined by multiplex PCR. Main outcome measures were insulin sensitivity, insulin secretion, serum lipids, and IGF-I levels. RESULTS: Insulin secretion was higher in children and adolescents with a least one GHRd3 allele, even after adjustment for age, sex, pubertal stage, and insulin sensitivity (P = 0.018). Disposition index was higher in GHRd3-positive subjects (P = 0.026). In addition, the GHRd3 allele was associated with higher triglyceride (P = 0.028), but not IGF-I levels. CONCLUSION: The presence of at least one GHRd3 allele was associated with higher insulin secretion for a given degree of insulin sensitivity in healthy children and adolescents during puberty. In addition, the presence of the GHRd3 allele was associated with a higher disposition index. Thus, this common polymorphism in the GHR gene might play a role for pancreatic beta-cell compensatory capacity.
U2 - 10.1210/jc.2009-0313
DO - 10.1210/jc.2009-0313
M3 - Journal article
C2 - 19417039
SN - 0021-972X
VL - 94
SP - 2966
EP - 2969
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 8
ER -