Patients with type 2 diabetes who experience frequent episodes of severe hypoglycemia are at risk of cardiac arrhythmias due to prolonged QT interval, according to a recent study reported in The Journal of Clinical Endocrinology & Metabolism.¹

To examine the association of severe hypoglycemia with corrected QT (QTc) interval prolongation in adults with type 2 diabetes, the researchers prospectively analyzed data of 8277 individuals, aged 62.6 years (mean) from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study database. None of the study subjects had QTc prolongation at baseline. Women comprised nearly 40% of the study population.

Over the follow-up period of two years, nearly 4% (n=324) out of the 8277 participants experienced at least one episode of severe hypoglycemia. Prolongation of QTc interval was seen in 517 participants over a median of 5 years. The risk of QTc prolongation increased by 66% among those who had suffered severe hypoglycemia with a relative risk of 1.66.

Compared to participants without history of severe hypoglycemia, QTc prolongation occurred in 10.3% of participants who reported one incident of severe hypoglycemia (RR 1.57), whereas among those who had two or more episodes of severe hypoglycemia, the incidence was higher (14.3%) (RR 2.01). This association was significant among participants younger than a median age of 61.9 years with RR of 2.63 but not among the older participants (≥61.9 years) with RR of 1.37.

The present study has demonstrated the elevated risk for QT interval prolongation during severe hypoglycemia among patients with type 2 diabetes. The activation of the sympathoadrenal system in response to hypoglycemia, which also mediates the cardiac arrhythmias may explain this association.

Diabetic autonomic neuropathy may increase the QT interval. Electrolyte disturbances may also cause prolonged QT intervals. It may also be drug-induced. However, the authors note that the QT interval prolongation in this study was independent of “other risk factors such as cardiac autonomic neuropathy”. The EURODIAB IDDM Complications Study had also earlier shown that QTc interval prolongation was independently associated with severe hypoglycemia in patients with type 1 diabetes.²

Prolonged QT interval is associated with an increased risk of ventricular tachyarrhythmias and may cause sudden cardiac death. The findings of this study are therefore clinically relevant because they enhance awareness about this potentially life-threatening risk of severe hypoglycemia.

References

1. Kaze AD, et al. Severe hypoglycemia and incidence of QT interval prolongation among adults with type 2 diabetes. J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2743-e2750. doi: 10.1210/clinem/dgac195.
2. Gabriella Gruden 1, et al. QTc interval prolongation is independently associated with severe hypoglycemic attacks in type 1 diabetes from the EURODIAB IDDM complications study. Diabetes Care. 2012 Jan;35(1):125-7. doi: 10.2337/dc11-1739.