Hypoglycaemia remains an inevitable risk in
insulin-treated
type 1 diabetes and
type 2 diabetes and has been associated with multiple adverse outcomes. Whether hypoglycaemia is a cause of fatal
cardiac arrhythmias in diabetes, or merely a marker of vulnerability, is still unknown. Since a pivotal report in 1991, hypoglycaemia has been suspected to induce
cardiac arrhythmias in patients with
type 1 diabetes, the so-called 'dead-in-bed syndrome'. This suspicion has subsequently been supported by the coexistence of an increased mortality and a three-fold increase in severe hypoglycaemia in patients with
type 2 diabetes receiving intensive
glucose-lowering treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Studies have investigated the association between hypoglycaemia-induced
cardiac arrhythmias. In a rat-model, severe hypoglycaemia resulted in a specific pattern of
cardiac arrhythmias including QT-prolongation,
ventricular tachycardia, second- and third-degree
AV block and ultimately cardiorespiratory arrest. In clinical studies of experimentally induced hypoglycaemia, QTc-prolongation, a risk factor of ventricular arrhythmias, is an almost consistent finding. The extent of QT-prolongation seems to be modified by several factors, including antecedent hypoglycaemia, diabetes duration and cardiac autonomic neuropathy. Observational studies indicate diurnal differences in the pattern of electrocardiographic alterations during hypoglycaemia with larger QTc-prolongations during daytime, whereas the risk of
bradyarrhythmias may be increased during sleep. Daytime periods of hypoglycaemia are characterized by shorter duration, increased awareness and a larger increase in
catecholamines. The counterregulatory response is reduced during nightly episodes of hypoglycaemia, resulting in prolonged periods of hypoglycaemia with multiple nadirs. An initial sympathetic activity at plasma
glucose nadir is replaced by increased vagal activity, which results in
bradycardia. Here, we provide an overview of the existing literature exploring potential mechanisms for hypoglycaemia-induced
cardiac arrhythmias and studies linking hypoglycaemia to
cardiac arrhythmias in patients with diabetes.