Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty

Kaspar Sørensen; Lise Aksglaede; Thor Munch-Andersen; Niels Jacob Aachmann-Andersen; Henrik Leffers; Jørn Wulff Helge; Linda Hilsted; Anders Juul

doi:10.1210/jc.2009-0313

Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty

Kaspar Sørensen, Lise Aksglaede, Thor Munch-Andersen, Niels Jacob Aachmann-Andersen, Henrik Leffers, Jørn Wulff Helge, Linda Hilsted, Anders Juul

24 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	94
Issue number	8
Pages (from-to)	2966-9
Number of pages	4
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2009-0313
Publication status	Published - 2009

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10.1210/jc.2009-0313

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Sørensen, K., Aksglaede, L., Munch-Andersen, T., Aachmann-Andersen, N. J., Leffers, H., Helge, J. W., Hilsted, L., & Juul, A. (2009). Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty. Journal of Clinical Endocrinology and Metabolism, 94(8), 2966-9. https://doi.org/10.1210/jc.2009-0313

Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty. / Sørensen, Kaspar; Aksglaede, Lise; Munch-Andersen, Thor et al.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 8, 2009, p. 2966-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Sørensen, K, Aksglaede, L, Munch-Andersen, T, Aachmann-Andersen, NJ, Leffers, H, Helge, JW , Hilsted, L & Juul, A 2009, 'Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 8, pp. 2966-9. https://doi.org/10.1210/jc.2009-0313

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title = "Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty",

abstract = "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.",

author = "Kaspar S{\o}rensen and Lise Aksglaede and Thor Munch-Andersen and Aachmann-Andersen, {Niels Jacob} and Henrik Leffers and Helge, {J{\o}rn Wulff} and Linda Hilsted and Anders Juul",

note = "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",

year = "2009",

doi = "10.1210/jc.2009-0313",

language = "English",

volume = "94",

pages = "2966--9",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

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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 -

Impact of the growth hormone receptor exon 3 deletion gene polymorphism on glucose metabolism, lipids, and insulin-like growth factor-I levels during puberty

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