Key result
Insulin aspart matches human insulin for post-hypoglycemia QTc increases but reduces QT dispersion.
Why the study?
Sudden death in young diabetic patients has been linked to nocturnal hypoglycaemia possibly due to cardiac dysrhythmias from abnormal cardiac repolarization during hypoglycaemia, necessitating comparison of effects of human soluble insulin and insulin aspart on cardiac repolarization.
Does insulin aspart reduce hypoglycaemia-induced alterations in cardiac repolarization compared to soluble human insulin in healthy males?
Does insulin aspart reduce hypoglycaemia-induced alterations in cardiac repolarization compared to soluble human insulin in healthy males?
Absolute Event Rate: 480% vs 480%
p-value: p=NS
Insulin aspart and soluble human insulin induce similar QTc prolongation during hypoglycemia, though insulin aspart is associated with slightly less QT dispersion.
Comparable QTc prolongation during hypoglycemia with both insulins warrants no practice change; leaves open clinical relevance of modestly reduced QT dispersion with aspart.
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.
No takes yet. Share an insight, caveat, or question.
Robinson et al. (2003) studied Healthy volunteers (n=17). Insulin aspart (IAsp) vs. Soluble human insulin (HI) was evaluated on QTc after hypoglycaemia (p=NS). Insulin aspart and soluble human insulin produced similar increases in QTc after hypoglycaemia (480 vs 480 ms), though QT dispersion was less pronounced with insulin aspart (92 vs 107 ms; P<0.05).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: