Comparison of LysB28, ProB29-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 LysB28,ProB29-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 GR (a measure of glucose corrected for differences in administered insulin dose: GR = glucose concentration X BMI X insulin dose-1) were followed for 4 h. RESULTS: The time courses of blood glucose concentration and GR 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, GR 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 GR values was 1.96 mol.kg.IU-1.m-5 (lispro <regular insulin, P = NS). Unexpectedly, the intrinsic variability of GR 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