BENEFICIAL METABOLIC EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I IN PATIENTS WITH SEVERE INSULIN-RESISTANT DIABETES TYPE-A

Severe insulin resistance type A is due to mutations in the insulin re ceptor gene and is characterized by glucose intolerance or diabetes me llitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recentl y, we showed that glucose levels in three such patients are promptly l owered by an iv bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare p atients again and determined fasting and postprandial glucose, insulin , C-peptide, proinsulin and lipid levels during five control, five tre atment and three wash-out days while on a constant diet. Treatment con sisted of 2 x 150 mu g rhIGF-I/kg sc per day, which elevated total IGF -I levels 4.5-fold above the control. Fasting glucose levels (days 1-5 ) in the two patients were 9.6 +/- 1.3 and 9.2 +/- 1.2 mmol/l, respect ively, and fell to 4.4 +/- 0.4 and 5.1 +/- 0.5 mmol/l on treatment day s 8-10. Fasting insulin (2950 +/- 450 and 690 +/- 125 pmol/l), C-pepti de (2217 +/- 183 and 1317 +/- 235 pmol/l) and proinsulin control level s (125 +/- 35 and 66 +/- 0 pmol/l) also decreased by similar to 65% du ring rhIGH-I treatment, as did the respective postprandial levels. Lip id levels hardly changed at all. In conclusion IGF-I appears to correc t partially some metabolic sequelae of severe insulin resistance and m ay, hence, be used as a new therapeutic agent.