ADVERSE-EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I IN OBESE INSULIN-RESISTANT TYPE-II DIABETIC-PATIENTS

Data from studies in diabetic rodents and evidence from clinical situa tions of severe resistance to insulin suggest that insulin-like growth factor I (IGF-I) is able to at least partly overcome insulin resistan ce, to assess the efficacy of recombinant human IGF-I in subjects with the most common form of insulin resistance, e.g., obese, type II diab etic patients, we administered recombinant human IGF-I (rhIGF) in dose s of 120 and 160 mu g/kg twice daily for 4-52 days to seven such indiv iduals who had been treated previously with high doses of insulin (>0. 7 U kg(-1) day(-1)). Four patients exhibited comparable or enhanced, w hereas three had diminished, blood glucose control on rhlGF-I relative to that while on twice daily NPH insulin during the six-week control period. The occurrence of adverse effects in all patients compelled us to discontinue rhlGF-I administration before completing the 8-week tr eatment period. These adverse effects included edema primarily of the face and hands, mild weight gain, occasional dyspnea, bilateral jaw te nderness, arthralgias and myalgias, fatigue, tachycardia, flushing, or thostatic hypotension, and local burning at the injection site. We con clude that the frequency and severity of side effects associated with administering high-dose subcutaneous rhIGF-I to obese insulin-resistan t diabetic patients make it an unacceptable therapeutic agent for thes e patients despite its ability to produce reasonable blood glucose con trol in similar to 50% of them.