The proarrhythmic effect of hypoglycemia: Evidence for increased risk from ischemia and bradycardia

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44 Scopus citations


Hypoglycemia increases the risk for both overall and sudden death. At a cellular level, hypoglycemia causes alterations in the physiology of myocardial tissue that are identical to proarrhythmic medications. Reduced serum glucose blocks the repolarizing K+ channel HERG, which leads to action potential and QT prolongation and is uniformly associated with risk for torsades de pointes ventricular tachycardia. The sympathetic response induced by hypoglycemia also increases the risk of arrhythmias from Ca2+ overload, which occur with sympathomimetic medications and excessive beta adrenergic stimulation. Thus, hypoglycemia can be considered a proarrhythmic event. This review focuses on emerging evidence for two other important changes induced by hypoglycemia that promote arrhythmias: ischemia and bradycardia. Studies of patients with "insulin shock" therapy from the early twentieth century and other more recent data strongly suggest that hypoglycemia can cause ischemia of myocardial tissue, both in association with coronary artery obstructions and by cellular mechanisms. Ischemia induces multiple proarrhythmic responses. Since ischemia itself reduces the possibility of using energy substrates other than glucose, hypoglycemia may generate positive feedback for electrophyisologic destabilization. Recent studies also show that hypoglycemia can cause bradycardia and heart block. Bradycardia is known to cause action potential prolongation and potentiate the development of torsades de pointes, particularly with low-serum K+ which can be induced by hypoglycemic episodes. Thus, hypoglycemia-induced bradycardia may also create a dynamic, positive feedback for the development of arrhythmias and sudden death. These studies further support the hypothesis that hypoglycemia is a proarrhythmic event.

Original languageEnglish (US)
Pages (from-to)5-14
Number of pages10
JournalActa Diabetologica
Issue number1
StatePublished - Feb 1 2014


  • Afterdepolarizations
  • Bradycardia
  • Diabetes
  • Hypoglycemia
  • Hypokalemia
  • Ischemia
  • Proarrhythmia
  • Sudden death
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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