RHIGF-I ADMINISTRATION IN HUMANS - DIFFERENTIAL METABOLIC EFFECTS OF BOLUS VS CONTINUOUS SUBCUTANEOUS DELIVERY

The metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I) were compared using bolus vs. continuous subcutaneous infu sions. Subjects (n = 5, 29 +/- 3 yr) received rhIGF-I as subcutaneous infusions by a Minimed pump (200 mu g . kg(-1) day(-1) over 16 h/day), and their data were compared with those of subjects (n = 6, 24 +/- 2 yr) who received subcutaneous 200 mu g . kg(-1) day(-1) injections twi ce a day. L-[1-C-14]leucine and [6,6-H-2(2)]glucose infusion studies a nd indirect calorimetry were performed, and total and free IGF-I, insu lin, and glucose concentrations were measured before and after 5-7 day s of rhIGF-I. Estimates of protein breakdown, oxidation, and synthesis did not change after pump therapy; in contrast, after bolus doses, pr otein oxidation decreased (P = 0.001) and whole body protein synthesis increased (P = 0.04). There was no change in lipid oxidation after pu mp treatment, whereas the bolus group had lower lipid oxidation (P = 0 .035). Both treatment modalities increased glucose oxidation (P < 0.02 ) and glucose production rates (P < 0.03). Overnight fasting insulin c oncentrations decreased in both groups, whereas plasma glucose remaine d invariant in the bolus group and decreased modestly in the pump grou p. Total IGF-I concentrations increased comparably in both groups, but the increase in free IGF-I was greater in the bolus-treated group (P = 0.001). We conclude that, in GH-sufficient postabsorptive individual s, the metabolic effects of rhIGF-I are in part dependent on the mode of administration, with a robust protein-anabolic effect when rhIGF-I is given as twice daily bolus injections but no detectable effect on p rotein turnover after a continuous mode of delivery. There were higher free IGF-I levels in the bolus-treated subjects, suggesting that this form of the molecule may be important for mediating IGF-I's protein-a nabolic effects at the tissue level. The data also suggest that carboh ydrate metabolism is more responsive than protein metabolism to the co ntinuous subcutaneous modality of rhIGF-I administration. Even though the mechanism of these differences in metabolic effects is not entirel y clear, it should be taken into account when patients are given rhIGF -I as prolonged treatment.