TRIAL OF INSULIN-LIKE GROWTH FACTOR-I THERAPY FOR PATIENTS WITH EXTREME INSULIN RESISTANCE SYNDROMES

Extreme insulin resistance occurs in patients with primary defects in insulin action at the receptor or postreceptor levels. The condition c ommonly is associated with acanthosis nigricans and ovarian masculiniz ation. Despite a marked increase in insulin secretion, some patients d evelop frank diabetes mellitus that does not respond adequately to ins ulin therapy. Insulinlike growth factor I exerts metabolic effects sim ilar to those of insulin. This study assessed the potential effectiven ess of IGF-I as a blood glucose lowering agent in patients with extrem e insulin resistance syndromes, including type A insulin resistance, c ongenital generalized lipodystrophy, and leprechaunism. Among the 11 p atients studied, some exhibited mutated insulin receptors, whereas oth ers were suspected to have defects in postreceptor sites. In each pati ent, plasma glucose levels decreased in response to subcutaneous injec tions of recombinant human IGF-I (0.1-0.3 mg/kg body wt). The degree o f the decrease was roughly comparable with that observed in normal ind ividuals. IGF-I also reduced plasma insulin concentrations. A long-ter m trial of IGF-I (up to 16 mo) showed that IGF-I (0.1-0.4 mg/kg body w t twice daily) is effective in lowering both fasting and postprandial plasma glucose concentrations with decreases in both fructosamine and HbA1c values. Improvement of acanthosis nigricans was observed in some of the patients. These results suggest that recombinant human IGF-I c ould be used clinically as a hypoglycemic agent in diabetic patients w ith extreme insulin resistance in whom insulin treatment is ineffectiv e.