Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia-induced alterations in cardiac repolarization

Br J Clin Pharmacol. 2003 Mar;55(3):246-51. doi: 10.1046/j.1365-2125.2003.01726.x.

Abstract

Aims: Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid-acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function.

Methods: A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 mm for 30 min and reduced to 2.5 mm after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4-6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter-regulatory hormones.

Results: The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean +/- SD 1.24 +/- 0.12 l h(-1) kg(-1), IAsp mean +/- s.d. 1.22 +/- 0.32 l h(-1) kg(-1)). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 +/- 37 ms vs 480 +/- 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 +/- 36 ms vs 107 +/- 42 ms; P < 0.05). Plasma adrenaline increased significantly and similarly after both insulins (initial and final concentration, HI, 0.23 +/- 0.01 to 4.87 +/- 0.48 nm, P < 0.001, IAsp, 0.24 +/- 0.01 to 4.99 +/- 0.48 nm, P < 0.001). Serum potassium decreased significantly but by a similar amount between the groups (initial and final concentration, HI, 4.18 +/- 0.3 to 4.2 +/- 0.2 mm, P < 0.001, IAsp, 4.2 +/- 0.3 to 4.2 +/- 0.3 mm, P < 0.001).

Conclusions: Soluble human insulin and insulin aspart had similar effects upon hypoglycaemia-induced alterations in cardiac repolarization, presumably because the effects of both regular insulin and insulin aspart on the sympathoadrenal response and potassium concentration were the same.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / prevention & control*
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / physiopathology
  • Electrophysiology
  • Epinephrine / blood
  • Glucagon / blood
  • Humans
  • Hypoglycemia / chemically induced*
  • Insulin / adverse effects*
  • Insulin / analogs & derivatives
  • Insulin Aspart
  • Male
  • Norepinephrine / blood
  • Potassium / blood
  • Ventricular Function

Substances

  • Insulin
  • Glucagon
  • Insulin Aspart
  • Potassium
  • Norepinephrine
  • Epinephrine