Short-term effects of recombinant human insulin-like growth factor I on metabolic control of patients with type II diabetes mellitus.
Recombinant human insulin-like growth factor I (rhIGF-I) lowers blood glucose, serum insulin, C-peptide, and lipid levels in healthy and diabetic animals and humans. We hypothesized that rhIGF-I might control blood glucose levels and concomitantly reduce pancreatic insulin secretion in patients with type II diabetes. If true, rhIGF-I might serve as a therapeutic agent that could mitigate some of the detrimental effects of hyperinsulinemia secondary to insulin resistance in these patients. In this study, we treated 12 patients with type II diabetes mellitus twice daily for 5 days with sc rhIGF-I in doses of 90, 120, or 160 micrograms/kg body weight. Metabolic parameters in the fasting and postprandial states were assessed during a 3-day baseline period, the rhIGF-I treatment period, and a 3-day follow-up period, respectively. Administration of rhIGF-I significantly reduced mean (+/- SD) concentrations of fasting blood glucose (12.3 +/- 4.5 to 9.1 +/- 2.6 mmol/L), serum insulin (98 +/- 52 to 56 +/- 27 pmol/L), and C-peptide (993 +/- 298 to 728 +/- 232 pmol/L). It also decreased postprandial (area under the curve) blood glucose (32.5 +/- 12.7 to 23.9 +/- 8.1 mmol/L.h), serum insulin (1102 +/- 707 to 467 +/- 332 pmol/L.h), and C-peptide (5958 +/- 2747 to 3442 +/- 1523 pmol/L.h). The administration of rhIGF-I was also associated with a small but significant reduction in serum triglycerides (6.76 +/- 3.45 to 5.32 +/- 2.59 mmol/L) and total cholesterol (6.13 +/- 1.25 to 5.66 +/- 1.20 mmol/L), 24-h creatinine clearance increased significantly (85 +/- 30 to 133 +/- 51 mL/min), and microalbuminuria was unchanged. Although rhIGF-I was reasonably well tolerated, side effects included low-grade edema, mild and mainly asymptomatic orthostatic hypotension, and bilateral temporomandibular tenderness. We conclude that short-term treatment of type II diabetic patients with rhIGF-I favorably affects metabolic control and enhances kidney function. An assessment of the risk/benefit ratio of rhIGF-I administration to this group of patients awaits extended experiments.
Schalch
D S
DS
Department of Medicine, University of Wisconsin, Madison 53792.
Turman
N J
NJ
Marcsisin
V S
VS
Heffernan
M
M
Guler
H P
HP
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I