Comparison of Lys(B28)Pro(B29)-human insulin analog and regular human insulin in the correction of incidental hyperglycemia

OBJECTIVE - To obtain clinically applicable data on the effects of regular human insulin and the Lys(B28),Pro(B29)-human insulin analogue (lispro) on the correction of incidental hyperglycemia. RESEARCH DESIGN AND METHODS - The insulins were compared in a non-clamped randomized crossover study of 27 male IDDM patients. Hyperglycemia was induced by the withdrawal of the normal evening dose of insulin; the next morning patients fasted and received a single dose of study insulin according to a dosing nomogram. Blood glucose concentration and G(R) (a measure of glucose corrected for differences in administered insulin dose: G(R) = glucose concentration x BMI x insulin dose(-1)) were followed for 4 h. RESULTS - The time courses of blood glucose concentration and G(R) were significantly different after regular insulin in comparison with lispro (multiple analysis of variance, P < 0.001). At t = 120 min, glucose concentrations had decreased 1.4 mmol/l more with lispro than with regular insulin (95% confidence interval [CI] 0.6-2.3, P = 0.002). Similarly, G(R) had decreased 4.4 mol . kg . IU-1. m(-5) more with lispro than with regular insulin (95% CI 2.6-6.2, P < 0.001). The overall difference in glucose values was 0.87 mmol/l (lispro < regular insulin, P = 0.036), and the overall difference in G(R) values was 1.96 mol . kg . IU-1. m(-5) (lispro < regular insulin, P = NS). Unexpectedly the intrinsic variability of G(R) was higher for lispro than for regular insulin. CONCLUSIONS - The more rapid action of lispro is an advantage in the correction of hyperglycemia, even though actual differences in glucose concentrations are smaller than suggested by previous clamped studies.