Background: With the use of intensive insulin therapy and insulin secretagogues to optimize
glycemic control in diabetes, hypoglycemia continues to present a clinical challenge. Hypoglycemia
has been implicated in nocturnal sudden death in type 1 diabetes, and the mechanism underlying
this is postulated to be cardiac arrhythmia.
Objective: This article reviews the evidence surrounding hypoglycemia and cardiac arrhythmia.
Methods: A structured search of the Pubmed bibliographic database was undertaken, and relevant peerreviewed
articles on the topic were included in the review.
Results: Since the initial description of nocturnal sudden death in type 1 diabetes over twenty years
ago, numerous studies have been performed to try and improve our understanding of the effects of hypoglycemia
on cardiac rhythm. This includes animal models of diabetes that have permitted valuable
insights into the pathophysiology of arrhythmia generation, involving direct effects of hypoglycemia
on the cardiac myocyte, effects from sympatho-adrenal activation and a reduced arrhythmia threshold.
In humans, the use of tools such as the hypoglycemic clamp or subcutaneous continuous glucose monitoring
have helped explore the interaction between hypoglycemia and cardiac rhythm in both controlled
and real world settings. Proving a causal link with fatal cardiac arrhythmia is clearly more difficult,
as simultaneous monitoring of cardiac rhythm and blood glucose level is rarely performed in this
setting. However substantial circumstantial evidence, including that from large randomized clinical trials,
exists to support the theoretical risk of arrhythmic death conferred by hypoglycemia. This has reshaped
opinion surrounding intensive glucose lowering in patients with diabetes and heart disease, and
is reflected in recent international guidelines.
Conclusion: This article reviews the postulated mechanisms, the extensive evidence base and the current
recommendations around hypoglycemia and arrhythmia.