Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: Effects on β -cell function and post-load glucose tolerance

Kevin Yuen, Nicholas Wareham, Jan Frystyk, Susie Hennings, Jo Mitchell, Linda Fryklund, David B. Dunger

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective: Modest elevations in circulating IGF-I levels have been suggested to protect against the development of glucose intolerance in insulin-resistant subjects. To further understand the interactions of GH and IGF-I on β-cell function and post-load glucose tolerance in glucose-intolerant subjects predisposed to diabetes, we performed a pilot study in 12 subjects with impaired glucose tolerance and the metabolic syndrome using a low GH dose (1.7 μg/kg per day) known to increase endogenous IGF-I production. Design: Fourteen daily GH or placebo injections in a double-blind cross-over study. Methods: Baseline and post-treatment oral glucose tolerance tests were performed. The homeostasis model assessment and the insulinogenic index was used to estimate fasting insulin sensitivity (SI) and β-cell function respectively, whereas changes in the incremental area under the curve were used to estimate post-load glucose tolerance (ΔAUCglu) and post-load insulin levels (ΔAUCins). Results: GH increased total IGF-I (P <0.02), free IGF-I (P <0.04) and fasting insulin (P <0.04) levels, but did not modify plasma IGF-binding proteins (IGFBPs)-1 and -3, fasting glucose, non-esterified fatty acid and C-peptide levels, and fasting SI. After oral glucose intake, glucose tolerance improved (P <0.03), but post-load insulin levels and β-cell function remained unchanged. Conclusion: Short-term low-dose GH administration induced fasting hyperinsulinaemia possibly by reducing insulin clearance but improved post-load glucose tolerance, suggesting that increased bioavailable IGF-I enhanced post-load SI without altering β-cell function. Longer-term studies are required to ascertain whether these positive effects on post-load glucose tolerance and the preservation of β-cell function can be sustained by this GH dose in these high-risk subjects.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalEuropean Journal of Endocrinology
Volume151
Issue number1
DOIs
StatePublished - Jul 2004
Externally publishedYes

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Glucose Intolerance
Growth Hormone
Insulin-Like Growth Factor I
Glucose
Fasting
Insulin
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
C-Peptide
Hyperinsulinism
Glucose Tolerance Test
Cross-Over Studies
Area Under Curve
Insulin Resistance
Blood Proteins
Homeostasis
Fatty Acids
Placebos
Injections

ASJC Scopus subject areas

  • Endocrinology

Cite this

Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome : Effects on β -cell function and post-load glucose tolerance. / Yuen, Kevin; Wareham, Nicholas; Frystyk, Jan; Hennings, Susie; Mitchell, Jo; Fryklund, Linda; Dunger, David B.

In: European Journal of Endocrinology, Vol. 151, No. 1, 07.2004, p. 39-45.

Research output: Contribution to journalArticle

Yuen, Kevin ; Wareham, Nicholas ; Frystyk, Jan ; Hennings, Susie ; Mitchell, Jo ; Fryklund, Linda ; Dunger, David B. / Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome : Effects on β -cell function and post-load glucose tolerance. In: European Journal of Endocrinology. 2004 ; Vol. 151, No. 1. pp. 39-45.
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AB - Objective: Modest elevations in circulating IGF-I levels have been suggested to protect against the development of glucose intolerance in insulin-resistant subjects. To further understand the interactions of GH and IGF-I on β-cell function and post-load glucose tolerance in glucose-intolerant subjects predisposed to diabetes, we performed a pilot study in 12 subjects with impaired glucose tolerance and the metabolic syndrome using a low GH dose (1.7 μg/kg per day) known to increase endogenous IGF-I production. Design: Fourteen daily GH or placebo injections in a double-blind cross-over study. Methods: Baseline and post-treatment oral glucose tolerance tests were performed. The homeostasis model assessment and the insulinogenic index was used to estimate fasting insulin sensitivity (SI) and β-cell function respectively, whereas changes in the incremental area under the curve were used to estimate post-load glucose tolerance (ΔAUCglu) and post-load insulin levels (ΔAUCins). Results: GH increased total IGF-I (P <0.02), free IGF-I (P <0.04) and fasting insulin (P <0.04) levels, but did not modify plasma IGF-binding proteins (IGFBPs)-1 and -3, fasting glucose, non-esterified fatty acid and C-peptide levels, and fasting SI. After oral glucose intake, glucose tolerance improved (P <0.03), but post-load insulin levels and β-cell function remained unchanged. Conclusion: Short-term low-dose GH administration induced fasting hyperinsulinaemia possibly by reducing insulin clearance but improved post-load glucose tolerance, suggesting that increased bioavailable IGF-I enhanced post-load SI without altering β-cell function. Longer-term studies are required to ascertain whether these positive effects on post-load glucose tolerance and the preservation of β-cell function can be sustained by this GH dose in these high-risk subjects.

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