title: Hypoglycaemia and QT interval prolongation in type 1 diabetes--bridging the gap between clamp studies and spontaneous episodes.
abstract: OBJECTIVE
  We propose a study design with controlled hypoglycaemia induced by subcutaneous injection of insulin and matched control episodes to bridge the gap between clamp studies and studies of spontaneous hypoglycaemia. The observed prolongation of the heart rate corrected QT interval (QTc) during hypoglycaemia varies greatly between studies.
  
  
  METHODS
  We studied ten adults with type 1 diabetes (age 41±15years) without cardiovascular disease or neuropathy. Single-blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a control episode on two occasions separated by 4weeks. QT intervals were measured using the semi-automatic tangent approach, and QTc was derived by Bazett's (QTcB) and Fridericia's (QTcF) formulas.
  
  
  RESULTS
  QTcB increased from baseline to hypoglycaemia (403±20 vs. 433±39ms, p<0.001). On the euglycaemia day, QTcB also increased (398±20 vs. 410±27ms, p<0.01), but the increase was less than during hypoglycaemia (p<0.001). The same pattern was seen for QTcF. Plasma adrenaline levels increased significantly during hypoglycaemia compared to euglycaemia (p<0.01). Serum potassium levels decreased similarly after insulin injection during both hypoglycaemia and euglycaemia.
  
  
  CONCLUSIONS
  Hypoglycaemia as experienced after a subcutaneous injection of insulin may cause QTc prolongation in type 1 diabetes. However, the magnitude of prolongation is less than typically reported during glucose clamp studies, possible because of the study design with focus on minimizing unwanted study effects.
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; Novo Nordisk A/S, Hilleroed, Denmark.
authors.forename: T F
authors.initials: TF
authors.lastname: Christensen
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; Department of Endocrinology and Internal Medicine/Medical Research Laboratory, Aarhus University Hospital, Denmark. Electronic address: simcich@hst.aau.dk.
authors.forename: S L
authors.initials: SL
authors.lastname: Cichosz
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark; Nordsjaellands Hospitaler, Hilleroed, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.affiliation: Novo Nordisk A/S, Hilleroed, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Randløv
authors.affiliation: Novo Nordisk A/S, Hilleroed, Denmark.
authors.forename: L E
authors.initials: LE
authors.lastname: Kristensen
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Struijk
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Eldrup
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: O K
authors.initials: OK
authors.lastname: Hejlesen
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000503:physiopathology; D004562:Electrocardiography; D015309:Glucose Clamp Technique / Q000009:adverse effects; D006329:Heart Conduction System / Q000002:abnormalities* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function
chemical_list: D007328:Insulin
keywords: Dead in bed; Hypoglycaemia; QT interval prolongation; Type 1 diabetes