title: Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes.
abstract: OBJECTIVE
  Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthening on the ECG; this may be important in the pathogenesis of sudden overnight death in young people with diabetes. Since hypoglycaemic QTc lengthening appears to be mediated through the sympathoadrenal response, we tested the hypothesis that beta1-blockade will prevent these changes in type 1 diabetic patients and so provide a potential therapeutic intervention.
  
  
  METHODS
  We studied eight type 1 diabetic adults without cardiovascular or renal complications. Similar hypoglycaemic clamp studies were performed on two occasions, at least 4 weeks apart, but immediately before one visit subjects received atenolol 100 mg daily for 7 days. Following a 60-min euglycaemic (5 mmol/l) period, blood glucose was lowered over 30 min to 2.5 mmol/l, and held for 60 min. High-resolution ECG was recorded at baseline and at 0, 30 and 60 min during each glycaemic plateau. QT interval was measured using a semiautomated tangent method and QTc was derived from QT using the Fridericia formula.
  
  
  RESULTS
  Mean (SD) baseline QTc was similar at both visits: control 391 (30) ms, post-atenolol 386 (34) ms; (p=0.33). Without atenolol pretreatment, QTc lengthened during hypoglycaemia to a maximum of 448 (34) ms (p<0.001). On atenolol, QTc lengthening was significantly reduced (peak QTc 413 (27) ms; p=0.004 vs control visit).
  
  
  CONCLUSIONS
  Hypoglycaemic QTc lengthening is blunted by atenolol in patients with type 1 diabetes. Selective beta1-blockade may help prevent sudden death, if we can identify those at high risk.
authors.affiliation: Division of Clinical Sciences, Northern General Hospital, University of Sheffield, Sheffield, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Lee
authors.forename: N D
authors.initials: ND
authors.lastname: Harris
authors.forename: R T
authors.initials: RT
authors.lastname: Robinson
authors.forename: C
authors.initials: C
authors.lastname: Davies
authors.forename: R
authors.initials: R
authors.lastname: Ireland
authors.forename: I A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: S R
authors.initials: SR
authors.lastname: Heller
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology*; D008297:Male; D013546:Sweating; D014202:Tremor
chemical_list: D000319:Adrenergic beta-Antagonists; D001262:Atenolol