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.