Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose.
Administration of insulin-like growth factor-I to patients with diabetes enhances insulin action and reduces the degree of hyperglycemia but it is associated with a high rate of adverse events. Infusion of the combination of rhIGFBP-3 (the principal binding protein for IGF-I in plasma) with rhIGF-I to patients with type I diabetes improved insulin sensitivity and was associated with a low incidence in side effects. In this study, 52 patients with insulin-treated type 2 diabetes received recombinant human IGF-I plus rhIGFBP-3 in one of four dosage regimens for 14 days. The four groups were: (1) continuous subcutaneous infusion of 2 mg/kg/day; (2) the same 2 mg/kg dose infused subcutaneously over 6 h between 2000 and 0200 h; (3) 1 mg/kg twice a day by bolus subcutaneous injection; (4) a single bedtime subcutaneous injection of 1 mg/kg. Across these four groups rhIGF-I/rhIGFBP-3 decreased insulin requirements between 54% and 82%. Fasting glucose decreased by 32-37%. Mean daily blood glucose (4 determinations per day) declined in all 4 groups (range 9-23% decrease). Frequent sampling for total IGF-I, free IGF-I and IGFBP-3 was performed on days 0,1,7,14 and 15. The peak total IGF-I values were increased to 4.0-4.8-fold at 16-24 h. For free IGF-I the increase varied between 7.1 and 8.2-fold and peak values were attained at 16-20 h after administration. Both the time to maximum concentration (Tmax) and the maximum free IGF-I levels (Cmax) on day 1 for all groups were substantially less than previously published studies, wherein lower doses of rhIGF-I were given without IGFBP-3. The improvement in glucose values and the degree of reduction in insulin requirement were the greatest in groups 2 and 3 and the patients in those groups had the highest free IGF-I levels. The frequency of side effects such as edema, jaw pain and arthralgias was 4% which is less than that has been reported in previous studies wherein IGF-I was administered without IGFBP-3. We conclude that rhIGF-I/rhIGFBP-3 significantly lowers insulin requirements yet improves glucose values and these changes may reflect improvement in insulin sensitivity. Coadministration of IGFBP-3 with IGF-I produces lower free IGF-I (Tmax and Cmax) levels compared to administration of IGF-I alone and is associated with relatively low incidence of side effects during 2 weeks of administration.
Clemmons
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DR
Division of Endocrinology, Department of Medicine, University of North Carolina, 6111A Thurston-Bowles, CB 7170, Chapel Hill, NC 27599, USA. endo@med.unc.edu
Moses
A C
AC
Sommer
A
A
Jacobson
W
W
Rogol
A D
AD
Sleevi
M R
MR
Allan
G
G
D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D005215:Fasting; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors
D001786:Blood Glucose; D004338:Drug Combinations; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I