Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia-induced alterations in cardiac repolarization.
OBJECTIVE
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.
Robinson
Robert T C E
RT
University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Sheffield S5 7AU, UK.
Harris
Nigel D
ND
Ireland
Robert H
RH
Lindholm
Anders
A
Heller
Simon R
SR
D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000503:physiopathology; D004594:Electrophysiology; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007328:Insulin / Q000009:adverse effects* / Q000031:analogs & derivatives; D061267:Insulin Aspart; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011188:Potassium / Q000097:blood; D016276:Ventricular Function
D007328:Insulin; D005934:Glucagon; D061267:Insulin Aspart; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine