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 language | English (US) |
|---|---|
| Pages (from-to) | 39-45 |
| Number of pages | 7 |
| Journal | European Journal of Endocrinology |
| Volume | 151 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 2004 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome
T2 - Effects on β -cell function and post-load glucose tolerance
AU - Yuen, Kevin
AU - Wareham, Nicholas
AU - Frystyk, Jan
AU - Hennings, Susie
AU - Mitchell, Jo
AU - Fryklund, Linda
AU - Dunger, David B.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=4344712843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4344712843&partnerID=8YFLogxK
U2 - 10.1530/eje.0.1510039
DO - 10.1530/eje.0.1510039
M3 - Article
C2 - 15248820
AN - SCOPUS:4344712843
VL - 151
SP - 39
EP - 45
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 1
ER -