TIME-ACTION PROFILES OF THE INTERMEDIATE-ACTING INSULIN ANALOG - DES(64,65)-HUMAN PROINSULIN

Des(64,65)-proinsulin (DPRO) is one of several endogenous intermediate s arising during the conversion of proinsulin to insulin. In pharmaceu tic preparations it is a clear solution containing no other proteins. Animal experiments and preliminary human studies indicated that DPRO s hould have a protracted time-action profile similar to that of NPH-ins ulin. Accordingly, we compared the time-action profiles of these two p reparations, using the euglycaemic glucose clamp-technique in 9 heathy male volunteers. Different doses of DPRO (0.1, 0.15, 0.2 U/kg) or equ ipotent doses of NPH (0.2, 0.3, 0.4 Uikg) were injected subcutaneously into the abdominal wall. The maximal metabolic effect (GIR(max)) of D PRO was greater than that of NPH-insulin (p < 0.05). With increasing d oses, GIR(max) differed significantly for DPRO but not for NPH-insulin . The lime to maximal metabolic effect (t(max)) was similar for the th ree doses of either preparation. However, t(max) was reached 30 min ea rlier with DPRO than with NPH-insulin (p<0.01). The decline to half-ma ximal after maximal activity was significantly faster with DPRO than w ith NPH-insulin (p<0.0001). Subcutaneous injection of DPRO thus produc ed a time-action profile between that of regular insulin and NPH-insul in.