METABOLIC EFFICACY OF PREPRANDIAL ADMINISTRATION OF LYS(B28), PRO(B29) HUMAN INSULIN ANALOG IN IDDM PATIENTS - A COMPARISON WITH HUMAN REGULAR INSULIN DURING A 3-MEAL TEST PERIOD

OBJECTIVE - The objective of this study was to compare the efficacy of the rapid-acting Lys(B28),Pro(B29) human insulin analog, insulin lisp ro, with currently available short-acting human insulin in a multiple injection therapy (MIT) regimen with respect to blood glucose and plas ma insulin profiles and to serum metabolites (lactate, free fatty acid s, glycerol, and beta-hydroxybutyrate) in 12 well-controlled type 1 di abetic subjects (8 male, HbA(1c) 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 crossov er study. Intermediate-acting insulin (NPH insulin) was given at bedti me. 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 treat ment periods, glycemic control was stable during lispro but improved d uring human insulin (Delta HbA(1c) lispro 0.1 +/- 0.48, NS; human insu lin -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 d emonstrated a faster rise after administration of lispro as compared w ith 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 low er insulin levels. CONCLUSIONS - Lispro insulin applied in an MIT regi men creates more physiologic insulin profiles and tends to lower the g lycemic excursions during the day compared with short-acting insulin. The analog can be applied safely in an MIT regimen, with mealtime inte rvals up to 5 h.