DUAL HORMONAL REPLACEMENT WITH INSULIN AND RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I IN IDDM - EFFECTS ON GLYCEMIC CONTROL, IGF-I LEVELS, AND SAFETY PROFILE

OBJECTIVE - To examine if dual replacement with insulin and rhIGF-I, r ecombinant human insulin-like growth factor I (rhIGF-I) may be safe an d result in improved metabolic control and reduced insulin usage. RESE ARCH DESIGN AND METHODS - Forty-three patients with IDDM were randomiz ed to receive a daily injection of rhIGF-I (80 mcg/kg s.c.) or placebo while on conventional insulin therapy far 4 weeks. insulin was adjust ed in the attempt to achieve predetermined goal glycemic values. Free and total IGF-I, four daily blood glucoses, and HbA(1c), were measured . RESULTS - Before randomization, placebo and rhIGP-I groups exhibited low plasma levels of free and total IGF-I, which increased toward nor mal levels during the treatment period only in the rhIGF group. The re gression curve obtained from the average of daily blood glucose measur ements indicated that the glycemic profile, overlapping in the lead-in period, exhibited a downward trend in the rhIGF-I group during the tr eatment period. Mean blood glucose level during the last 10 days of tr eatment was lower in the rhIGF-I groups (174 +/- 37 vs. 194 +/- 32 mg/ dl). HbA(1c) level was reduced by more than one-half percent more in t he rhIGF-I group (-1.85%) than in the control group (-1.3%). The dose of regular insulin was significantly lower in the rhIGF-I group (0.2 /- 0.1 vs. 0.28 +/- 0.1 U . kg(-1). 10 days(-1) in the placebo group; P < 0.05). CONCLUSIONS - rhIGF-I in combination with conventional insu lin treatment ameliorated the low plasma total and free IGF-I levels a nd was well tolerated in ZDDM. There was a trend toward improved glyce mic control, while the regular insulin dose was significantly decrease d.