title: Glucose ingestion causes cardiac repolarization disturbances in type 1 long QT syndrome patients and healthy subjects.
abstract: Both hypoglycemia and severe hyperglycemia constitute known risk factors for cardiac repolarization changes potentially leading to malignant arrhythmias. Patients with loss of function mutations in KCNQ1 are characterized by long QT syndrome (LQTS) and may be at increased risk for glucose-induced repolarization disturbances.
  
  
  
  The purpose of this study was to test the hypothesis that KCNQ1 LQTS patients are at particular risk for cardiac repolarization changes during the relative hyperglycemia that occurs after an oral glucose load.
  
  
  
  Fourteen KCNQ1 LQTS patients and 28 control participants matched for gender, body mass index, and age underwent a 3-hour oral 75-g glucose tolerance test with ECGs obtained at 7 time points. Fridericia corrected QT interval (QTcF), Bazett corrected QT interval (QTcB), and the Morphology Combination Score (MCS) were calculated.
  
  
  
  QTc and MCS increased in both groups. MCS remained elevated until 150 minutes after glucose ingestion, and the maximal change from baseline was larger among KCNQ1 LQTS patients compared with control subjects (0.28 ± 0.27 vs 0.15 ± 0.13; P <.05).
  
  
  
  Relative hyperglycemia induced by ingestion of 75-g glucose caused cardiac repolarization disturbances that were more severe in KCNQ1 LQTS patients compared with control subjects.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Hyltén-Cavallius
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Eva W
authors.initials: EW
authors.lastname: Iepsen
authors.affiliation: Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Graff
authors.affiliation: Research Centre for Prevention and Health, The Capital Region, Copenhagen, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Signe S
authors.initials: SS
authors.lastname: Torekov
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Cardiology S, Gentofte University Hospital, Copenhagen, Denmark. Electronic address: jkanters@sund.ku.dk.
authors.forename: Jørgen K
authors.initials: JK
authors.lastname: Kanters
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D029597:Romano-Ward Syndrome / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D013549:Sweetening Agents / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D013549:Sweetening Agents; D005947:Glucose
keywords: Cardiac arrhythmia; KCNQ1; Long QT syndrome; Morphology Combination Score; Oral glucose tolerance test; QT interval; T-wave morphology