Cardiac repolarization during hypoglycaemia in type 1 diabetes: impact of basal renin-angiotensin system activity

Aims Hypoglycaemia-induced cardiac arrhythmias may be involved in the pathogenesis of the 'dead-in-bed syndrome' in patients with type 1 diabetes. Evidence suggests that the renin-angiotensin system (RAS) influences the occurrence of arrhythmias. The aim of this study was to explore if basal RAS activity affects cardiac repolarization during hypoglycaemia, thereby potentially carrying prognostic information on risk of the 'dead-in-bed syndrome'. Methods and results Nine subjects with high RAS activity and nine subjects with low RAS activity were subjected to single-blinded placebo-controlled hypoglycaemia (nadir plasma glucose 2.4 mmol/L). QTc/QTcF and QT dynamics were registered by Holter monitoring. QTc prolonged during [8 (+/- 2.3) ms, P < 0.01] and after [11 (+/- 3) ms, P < 0.001] hypoglycaemia. Dynamic QT parameters reacted ambiguously. Low RAS activity was associated with a slightly more pronounced QT prolongation [6 (+/- 3) ms, P = 0.04]. Adrenaline tended to increase more in the low-RAS group (P = 0.08) and was correlated to QTc (r = 0.67, P < 0.01) and QTcF (r = 0.58, P < 0.05) during hypoglycaemia. Conclusion Low basal RAS activity may be associated with a slightly more pronounced QT prolongation during hypoglycaemia, when compared with high RAS activity. The impact, however, is modest and the clinical consequence is unclear.