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 dia betic animals and humans. We hypothesized that rhIGF-I might control b lood glucose levels and concomitantly reduce pancreatic insulin secret ion in patients with type II diabetes. If true, rhIGF-I might serve as a therapeutic agent that could mitigate some of the detrimental effec ts of hyperinsulinemia secondary to insulin resistance in these patien ts. In this study, we treated 12 patients with type II diabetes mellit us twice daily for 5 days with sc rhIGF-I in doses of 90, 120, or 160 mu g/kg body weight. Metabolic parameters in the fasting and postprand ial states were assessed during a 3-day baseline period, the rhIGF-I t reatment period, and a 3-day follow-up period, respectively. Administr ation of rhIGF-I significantly reduced mean (+/- so) concentrations of fasting blood glucose (12.3 +/- 4.5 to 9.1 +/- 2.6 mmol/L), serum ins ulin (98 +/- 52 to 56 +/- 27 pmol/L), and C-peptide (993 +/- 298 to 72 8 +/- 232 pmol/L). It also decreased postprandial (area under the curv e) blood glucose (32.5 +/- 12.7 to 23.9 +/- 8.1 mmol/L.h), serum insul in (1102 +/- 707 to 467 +/- 332 pmol/L.h), and C-peptide (5958 +/- 274 7 to 3442 +/- 1523 pmol/L.h). The administration of rhIGF-I was also a ssociated with a small but significant reduction in serum triglyceride s (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 eff ects included low-grade edema, mild and mainly asymptomatic orthostati c hypotension, and bilateral temporomandibular tenderness. We conclude that short-term treatment of type II diabetic patients with rhIGF-I f avorably affects metabolic control and enhances kidney function. An as sessment of the risk/benefit ratio of rhIGF-I administration to this g roup of patients awaits extended experiments.