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

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.