Dose-response studies with biosynthetic human growth hormone (GH) in GH-deficient patients.
Increasing doses of biosynthetic human GH (R-hGH) were given sc to seven GH-deficient patients for three consecutive 14-day periods (2, 4, and 6 IU/day at 2000 h), followed by 14 days of no GH therapy. At the end of each period each patient was hospitalized for frequent blood sampling from 2000 to 1100 h the following day. A dose-dependent increase in serum GH and serum insulin-like growth factor I (IGF-I) levels occurred. However, the time course of the serum IGF-I concentrations was different on the four occasions; there was a significant fall in the evening when no therapy was given (P less than 0.01), a significant increase after injections of 2 IU R-hGH, and constant levels during treatment with 4 and 6 IU R-hGH. Plasma glucose levels were within the normal range, with a significantly lower fasting level (at 0400 h) when no GH was given. Breakfast induced a plasma glucose rise when GH was administered, but no rise without GH, and a postprandial serum insulin response that was GH dose dependent. GH therapy increased serum FFA (P less than 0.05) and blood 3-hydroxybutyrate levels, but had no effect on blood alanine or lactate or serum triglyceride and cholesterol levels. We conclude that the serum IGF-I response to GH is dose dependent, and that a GH replacement dose of 2 IU/day (equalling 1.5 IU/m2.day) is insufficient to maintain normal diurnal serum IGF-I levels. Furthermore, a GH-independent diurnal variation in serum IGF-I in these patients is suggested. This GH preparation also has diabetogenic and lipolytic actions.
Jørgensen
J O
JO
Institute of Experimental Clinical Research, Second University Clinic of Internal Medicine, Kommunehospital, Aarhus, Denmark.
Flyvbjerg
A
A
Lauritzen
T
T
Alberti
K G
KG
Orskov
H
H
Christiansen
J S
JS
D020155:3-Hydroxybutyric Acid; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005247:Feeding Behavior / Q000502:physiology; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency*; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D011994:Recombinant Proteins; D014280:Triglycerides; D013006:Growth Hormone; D005934:Glucagon; D002784:Cholesterol; D000409:Alanine; D020155:3-Hydroxybutyric Acid