Counterregulatory hormone responses and symptoms during hypoglycaemia induced by porcine, human regular insulin, and Lys(B28), Pro(B29) human insulin analogue (insulin Lispro) in healthy male volunteers.

Abstract

Lys(B28)Pro(B29) human insulin analogue (Lispro) is a newly developed monomeric insulin analogue with a rapid onset and short duration of action. The aim of the study was to compare the thresholds for the counterregulatory responses during a stepwise euglycaemic/hypoglycaemic clamp for insulin lispro (LP), human (H), and porcine (P) insulin in a randomized order in 12 healthy male volunteers (age 22.4 +/- 1.7 years, BMI 21.9 +/- 1.7 kg m-2). A euglycaemic period of 2 h was followed by three hypoglycaemic levels of 60 min each; from 150-210 min at 3.5 mmol l-1, 240-300 min at 3.0 mmol l-1 and 330-390 min at 2.5 mmol l-1. Plasma insulin levels during the 50 mU kg-1 h-1 infusions and blood glucose levels were not significantly different. The glucose requirements (mean +/- SD) during the last part of the euglycaemic period (90-120 min) tended to be higher during LP compared to those during H and P; 2239 +/- 702 and 1929 +/- 769, 1957 +/- 725 mg kg-1, P = 0.067, respectively. The thresholds (blood glucose level at which a sustained elevation of the counterregulatory hormones as compared to the mean at normoglycaemia level 4.0 mmol l-1, occurs) for the various hormones were very similar during LP, H, and P insulin infusions and occurred at 253.8 +/- 56.7, 256.3 +/- 55.3 and 257.5 +/- 70.0 min for adrenaline; 241.4 +/- 80.3, 260.5 +/- 82.5 and 225.0 +/- 75.9 min for noradrenaline; 307.5 +/- 65.5, 304.1 +/- 74.1 and 322.5 +/- 40.4 min for cortisol; 263.8 +/- 50.3, 255.0 +/- 63.6 and 249.6 +/- 50.9 min for growth hormone; 236.3 +/- 78.2, 200.0 +/- 73.1 and 226.3 +/- 65.5 for pancreatic polypeptide. The autonomic and neuroglycopenic symptoms were elicited at 240 and 300 min, respectively. In conclusion, our data indicate a tendency to a higher biological activity of approximately 10% for Lispro insulin. During a stepwise euglycaemic/hypoglycaemic clamp, the counterregulatory hormone responses to insulin lispro, human insulin, and porcine insulin were similar.