Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance.
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 beta-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 microg/kg per day) known to increase endogenous IGF-I production.


METHODS
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 (S(I)) and beta-cell function respectively, whereas changes in the incremental area under the curve were used to estimate post-load glucose tolerance (DeltaAUC(glu)) and post-load insulin levels (DeltaAUC(ins)).


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 S(I). After oral glucose intake, glucose tolerance improved (P<0.03), but post-load insulin levels and beta-cell function remained unchanged.


CONCLUSIONS
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 S(I) without altering beta-cell function. Longer-term studies are required to ascertain whether these positive effects on post-load glucose tolerance and the preservation of beta-cell function can be sustained by this GH dose in these high-risk subjects.
Yuen
Kevin
K
University Department of Paediatrics, Addenbrooke's Hospital, Cambridge, UK.
Wareham
Nicholas
N
Frystyk
Jan
J
Hennings
Susie
S
Mitchell
Jo
J
Fryklund
Linda
L
Dunger
David
D
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D011446:Prospective Studies
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I