To determine whether the long-term use of insulin lispro (LP) affects the counterregulatory hormone response to hypoglycemia.


Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9 ± 0.48; mean HbA1c 7.84 ± 0.25%) with IDDM, treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a double-blind, crossover design. Patients were randomized to LP or human regular insulin (HR) for 3 months and then crossed over to the other insulin for an additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch, and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were evaluated at the end of each treatment period.


HbA1c was significantly lower with LP versus HR (7.47 ± 0.28% vs. 7.9 ± 0.26%, P = 0.04). The incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l and/or symptoms) during the last month of the study was significantly lower with LP versus HR (8.7 ± 2.9 vs. 11.8 ± 2.9, P = 0.03). The total daily insulin dosage was not different in the two treatment periods. There was no episode of severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol, glucagon, and epinephrine responses during the same period of hypoglycemia were not different for each treatment period.


The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia.

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