Study of Recombinant Human Insulin-Like Growth Factor I in Patients With Severe Insulin Resistance

OBJECTIVES: I. Determine the efficacy and toxic effects of recombinant human insulin-like growth factor I (rhIGF-I) on carbohydrate tolerance, insulin action, insulin secretion, hyperandrogenism, and hyperlipidemia in patients with severe insulin resistance who have failed other therapies. II. Determine the dose and time response of rhIGF-I on carbohydrate homeostasis and secondary abnormalities in this patient population. III. Determine the effect of rhIGF-I on insulin clearance, the regulation of insulin-like growth factor binding protein 1, the regulation of sex hormone binding globulin, and hypothalamic pituitary gonadal axis in this patient population.

PROTOCOL OUTLINE: This is an open label study. Patients receive the first dose of subcutaneous recombinant human insulin-like growth factor I (rhIGF-I) on day 7. Patients receive rhIGF-I twice daily 15-30 minutes before breakfast and dinner, and are hospitalized for the first week of therapy. Patients return for an outpatient exam on day 19 of rhIGF-I therapy. Approximately 30 days into the therapy, patients are readmitted to the clinical center for repeat screening tests. Patients then receive maintenance therapy of rhIGF-I for up to 6-12 months. A washout period follows the maintenance therapy phase. Patients are followed weekly, biweekly, or monthly depending on blood glucose response of patients off rhIGF-I therapy. Weekly phone contact with study coordinator is mandatory during this time. Completion date provided represents the completion date of the grant per OOPD records

PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Hematologically proven severe insulin resistance with or without diabetes Fasting insulin greater than 40 U/mL Post glucose insulin greater than 300 U/mL (unless overt diabetes mellitus is present) --Prior/Concurrent Therapy-- Endocrine therapy: No concurrent oral hypoglycemic agents and/or insulin Other: No concurrent birth control pills --Patient Characteristics-- Not pregnant Negative pregnancy test Effective barrier contraceptive method must be used by fertile patients Good health