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

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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.