Comparison of Human Regular and Lispro Insulins After Interruption of Continuous Subcutaneous Insulin Infusion and in the Treatment of Acutely Decompensated IDDM

OBJECTIVE: To compare the rapidity of metabolic decompensation after interruption of CSII between human regular and lispro insulin and to compare these two insulins in the correction of the hyperglycemia and ketosis of mildly decompensated IDDM. Lispro insulin may be especially useful for insulin pump therapy (continuous subcutaneous insulin infusion [CSII]). RESEARCH DESIGN AND METHODS: A total of 18 patients with well-controlled IDDM (HbA1c 7.7 +/- 1.1%, age 30 +/- 11 years) were studied. All were being treated with CSII (nine with human regular and nine with lispro insulin). The study consisted of two phases: 1) an insulin interruption phase, in which the basal insulin infusion was stopped (at 0300) and plasma insulin, glucose, and beta-O-hydroxybutyrate (beta-OHB) were measured every 15-60 min for 6 h after interruption of the insulin infusion and 2) an insulin replacement phase, which involved measuring plasma insulin, glucose, and beta-OHB for 2 h after a single injection of either human regular or lispro insulin to correct the hyperglycemia and ketosis that developed during the first phase of the study. RESULTS: After interruption of the basal insulin infusion during the insulin interruption phase, plasma insulin levels fell gradually in both groups to nadir values of 1.6 +/- 0.8 and 2.0 +/- 1.2 microU/ml in the regular insulin- and insulin lispro-treated groups, respectively. Plasma glucose concentrations rose to 13.8 +/- 1.9 and 16.0 +/- 1.7 mmol/l in the regular insulin- and insulin lispro-treated groups, respectively. No significant differences were seen between the therapy groups at any time in the insulin levels or in the concentrations of plasma glucose or beta-OHB. In the insulin replacement phase, insulin levels rose more rapidly in those treated with lispro insulin, reaching a greater peak value (e.g., at 60 min, plasma insulin 25 +/- 3.4 vs. 15.6 +/- 2.6 microU/ml, P < 0.05). In association with this, plasma glucose decreased to a lower nadir after lispro insulin (9.7 +/- 0.4 vs. 13.7 +/- 0.7 mmol/l, lispro- vs. regular-treated groups at 120 min after insulin administration, P < 0.01). beta-OHB levels decreased rapidly in both groups. CONCLUSIONS: In patients treated with CSII, interruption of the basal insulin infusion in the middle of the night does not result in more rapid metabolic decompensation in patients treated with lispro compared with those treated with regular human insulin. Lispro insulin is effective in treating mild ketosis and hyperglycemia, and its rapid action may be advantageous in the "sick day" management at home of patients with IDDM.