title: Hypoglycemia and Cardiac Arrhythmia; Mechanisms, Evidence Base a nd Current Recommendations.
abstract: 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.
  
  
  CONCLUSIONS
  This article reviews the postulated mechanisms, the extensive evidence base and the current recommendations around hypoglycemia and arrhythmia.
authors.affiliation: Department of Cardiology, Guy' s and St Thomas' NHS Foundation Trust, London. United Kingdom.
authors.forename: Sitara G
authors.initials: SG
authors.lastname: Khan
authors.affiliation: Department of Diabetes, The Royal London Hospital, Barts Health NHS Trust, London. United Kingdom.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Huda
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D001786:Blood Glucose; D016757:Death, Sudden, Cardiac / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D004562:Electrocardiography; D006801:Humans; D007003:Hypoglycemia / Q000150:complications* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic
chemical_list: D001786:Blood Glucose
keywords: Arrhythmia; cardiac; diabetes; hypoglycemia; insulin; sudden death