The effects of short-term administration of two low doses versus the standard GH replacement dose on insulin sensitivity and fasting glucose levels in young healthy adults.
GH has both diabetogenic and insulin-like actions. Supraphysiological GH doses are known to reduce insulin sensitivity (S(I)), but lower doses are less well studied. We therefore compared the effects of two physiological GH doses (intermediate, 0.0033 mg/kg x d; low, 0.0017 mg/kg x d) with the standard adult GH deficiency replacement dose (standard, 0.008 mg/kg x d) on S(I), beta-cell function, IGF-I, and IGF binding proteins (IGFBPs)-1 and -3 in healthy adults. Eleven healthy nonobese volunteers (4 males and 7 females, aged 21-38 yr) received 7 daily injections of the standard and intermediate GH doses, and 10 (5 males and 5 females, aged 21-38 yr) received the low dose. Fasting blood samples were collected daily (days 1-8). S(I) and beta-cell function were calculated using the Homeostasis model assessment. All GH doses increased IGF-I and IGFBP-3 levels, with the standard dose inducing the greatest rise (P < 0.001). At day 2 vs. baseline, all three doses increased the IGF-I/IGFBP-3 ratio, but only the standard dose lowered IGFBP-1 levels (P = 0.03). The standard dose reduced S(I) (P = 0.01), whereas the intermediate dose increased S(I) (P < 0.005) and lowered fasting insulin levels (P < 0.01). The low dose did not modify S(I), but reduced fasting glucose levels (P < 0.0001) and increased beta-cell function (P = 0.001). Males demonstrated higher IGF-I and IGFBP-3 responsiveness to the standard dose than females. Males also showed greater increase in S(I) and decrease in fasting glucose levels on both intermediate and low doses. In conclusion, the metabolic effects of GH are dose- and gender-dependent. The standard adult GH deficiency replacement dose induced insulin resistance, whereas lower doses improved S(I), especially in males. The low GH dose lowered fasting glucose levels and could represent the optimal dose to stimulate beta-cell function without compromising S(I) in insulin-resistant GH-deficient adults.
Yuen
Kevin
K
University Department of Pediatrics, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom.
Ong
Ken
K
Husbands
Sandra
S
Chatelain
Pierre
P
Fryklund
Linda
L
Gluckman
Peter
P
Ranke
Michael
M
Cook
David
D
Rosenfeld
Ron
R
Wass
John
J
Dunger
David
D
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005215:Fasting / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy; D012016:Reference Values; D012727:Sex Characteristics
D001786:Blood Glucose; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose