Metabolic Efficacy of Preprandial Administration of Lys(B28), Pro(B29) Human Insulin Analog in IDDM Patients: A comparison with human regular insulin during a three-meal test period

Abstract

OBJECTIVE The objective of this study was to compare the efficacy of the rapid-acting Lys(B28), Pro(B29) human insulin analog, insulin lispro, with currently available short-acting human insulin in a multiple injection therapy (MIT) regimen with respect to blood glucose and plasma insulin profiles and to serum metabolites (lactate, free fatty acids, glycerol, and β-hydroxybutyrate) in 12 well-controlled type 1 diabetic subjects (8 male, HbA1c 6.8 ± 0.9% [mean ± SD]). RESEARCH DESIGN AND METHODS After a run-in period of 4 weeks, patients were treated with either lispro at mealtime or human insulin 30 min before the meal for two periods of 4 weeks in a randomized open-label crossover study. Intermediate-acting insulin (NPH insulin) was given at bedtime. At the end of both study periods, metabolic profiles were assessed from 10:00 P.M. to 7:00 P.M. the next day. RESUlTS During the treatment periods, glycemic control was stable during lispro but improved during human insulin (ΔHbA1c lispro 0.1 ± 0.48, NS; human insulin −0.41 ± 0.34%, P < 0.05). Glucose excursions, as measured by the incremental AUC, during the day and for the 2-h postprandial periods, were lower, although not significantly, for lispro. Insulin profiles demonstrated a faster rise after administration of lispro as compared with human insulin, peaking at 61 ± 11.9 and 111 ± 48.1 min (P < 0.01). Glycerol levels showed a slight increase before lunch and dinner, suggestive of enhanced lipolytic activity and compatible with the lower insulin levels. CONCLUSIONS Lispro insulin applied in an MIT regimen creates more physiologic insulin profiles and tends to lower the glycemic excursions during the day compared with short-acting insulin. The analog can be applied safely in an MIT regimen, with mealtime intervals up to 5 h.