O-015. rhIGF-I: Differential sensitivity to SQ bolus vs continuous delivery

The metabolic effects of rhIGF-I were compared using subcutaneous (SQ) bolus vs continuous infusions. Subjects received rhIGF-I as SQ infusions using a Minimed® pump in doses of 120-200 μg/kg/d for 12-16 h/d (n = 9, 32±2 yr) and data compared with those who received 200 μg/kg/d ÷ bid SQ (n = 6). ¹⁴C-leucine, ²H₂-glucose tracer studies and indirect calorimetry were performed, as well as measurement of total and 'free' IGF-I, insulin and glucose concentrations, before and after 5-7 d (bolus group) or 6 d (pump group) of rhIGF-1. Estimates of protein breakdown, oxidation and synthesis did not change after pump therapy as compared to the decrease in oxidation (p = 0.001) and increase in whole body protein synthesis (p = 0.04) observed after bolus doses. Both groups had a modest trend towards lower lipid oxidation (p = 0.07, both) and increased their glucose oxidation (p<0.02) and glucose production rates (Ra) (p<0.04) after therapy. Insulin concentrations substantially decreased in both groups, whereas plasma glucose remained invariant. Total and 'free' IGF-I concentrations increased comparably in both groups, but the delta increase in 'free' IGF-I was higher in the bolus treated group (p = 0.001). We conclude, that continuous SQ delivery of rhIGF-I is as effective as bolus doses given bid in increasing glucose oxidation, however pump therapy was ineffective enhancing whole body protein anabolism as compared to SQ bolos injections. Ellis differential sensitivity in metabolic effects should be taken into account when giving rhIGF-I to patients as prolonged treatment.