Treatment of NIDDM IDDM, and other insulin-resistant states with IGF-I: Physiological and clinicaI considerations

Insulin like growth factor I (IGF-I) is a small, 70 amino acid peptide that mimics many of the effects of insulin on carbohydrate, lipid, and protein metabolism. IGF-I and its binding proteins (IGFBPs) function as a complementary system to insulin in the maintenance of glucose homeostasis. Availability of human IGF-I through recombinant DNA technology (rhIGF-I) has allowed investigators to examine the function of the IGF/IGFBP system and to evaluate its potential role as a therapeutic intervention to normalize disturbed fuel metabolism in a variety of glucose-intolerant states. In vitro and in vivo studies have established the insulinomimetic actions of rhIGF-I and its ability to enhance glucose uptake and stimulate intracellar pathways of glucose metabolism. Recognition of IGF-I's stimulatory effect on glucose metabolism has kindled interest in its use as a therapeutic agent to enhance insulin sensitivity and improve glucose tolerance in a variety of insulin resistant states, including growth hormone-induced insulin resistance in adolescents with IDDM; poorly controlled NIDDM patients; individuals with genetic syndromes of extreme insulin resistance; and highly catabolic, severely ill insulin resistant patients suffering from trauma injuries, surgical complications, sepsis, and other catastrophic medical illnesses. Other clinical applications that are being considered include the use IGF-I to treat acquired immunodeficiency syndrome (AIDS) cachesia and osteoporosis. When used in moderate doses, rhIGF-I has proven to be safe, and in many instances impressive therapeutic benefits have been reported. Not surprisingly, hypoglycemia is the most common side effect. The potential for IGF-I to stimulate cell proliferation and accelerate diabetic vascular complications remains an unresolved issue. Future studies are needed to determine the efficacy and safety of long-term rhIGF-I administration in the treatment of insulin resistant states.