Hypoglycaemia and cardiac arrhythmias in diabetes

Abstract

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.

Age- and sex-specific profiles of temporal fasting plasma glucose variability in a population undergoing routine health screening

“…Reduced glycemic exposure affected the development and progression of microvascular complications of diabetes were reported in the Diabetes Control and Complications Trial [ 9 ] and the UK Prospective Diabetes Study [ 10 ]. Hypoglycemia has been linked to cardiovascular events and increased dementia [ 11 , 12 ]. Impaired glucose tolerance and impaired fasting glycemia are risks for the future development of diabetes and cardiovascular disease.…”

Nocturnal Hypoglycaemia in Patients with Diabetes Mellitus: Database Analysis of a Cohort Using Telemedicine Support for Self-Monitoring of Blood Glucose over a 10-Year-Long Period

“…Nocturnal hypoglycaemia is one of the most feared complications of diabetes treatment [ 25 , 26 ]. The dead-in-bed syndrome is attributed, at least in some cases, to unrecognized nocturnal hypoglycaemia-induced cardiac rhythm disturbances [ 27 , 28 , 29 ]. Repeated hypoglycaemic episodes may be involved in the pathomechanism of cognitive dysfunction, both in type 1 and type 2 diabetes [ 30 , 31 ].…”

Circadian Mechanisms: Cardiac Ion Channel Remodeling and Arrhythmias

“…Therefore, prolonged sympathetic activity in diabetic patients may counteract the protective effect of parasympathetic tone on the cardiovascular system, which normally would then be manifested by a lower incidence of cardiac events during the nighttime ( Bernardi et al, 1992 ). Diurnal differences in the ECG have been observed during hypoglycemia and this is generally manifested as a larger prolongation in QT c interval throughout the daytime, suggesting a higher vulnerability to arrhythmias; while the incidence of bradycardia episodes was found to be increased during the sleep cycle ( Andersen et al, 2020 ).…”