title: QT prolongation caused by insulin-induced hypoglycaemia - An interventional study in 119 individuals.
abstract: OBJECTIVE
  Hypoglycaemia is associated with increased risk of cardiovascular events and mortality in patients with diabetes, but the extent and mechanisms of this link are ill defined. We here prospectively studied cardiac repolarization abnormalities during insulin-induced hypoglycaemia in humans.
  
  
  METHODS
  119 individuals (69 males, age 47.5±13.4years, range 18-82years) were assessed during hypoglycaemia after the injection of 0.1-0.25units/kg human insulin. Corrected QT intervals (QTc) and QT dispersion (QTd) were calculated from serially recorded twelve lead electrocardiograms, and plasma glucose and other endocrine markers were studied.
  
  
  RESULTS
  QTc increased from 415.1±21.9ms (mean±standard deviation) at baseline to 444.9±26.5ms during hypoglycaemia (plasma glucose nadir, 1.6±0.5mmol/L, p=0.001), accompanied by an increase of QTd from 45.0±22.7ms to 64.1±40.0ms (p<0.001). Hypoglycaemia-induced abnormal QTc prolongation (defined as ⩾460ms in females and ⩾450ms in males) occurred in 17% (9/54) of females and 26% (17/65) of males. 97 of 119 of individuals (82%) developed transient hypokalaemia (K+⩽3.6mmol/L), and plasma epinephrine increased from 220.4±169.5pmol/L at baseline to 2945.6±2421.4pmol/L during hypoglycaemia. Baseline QTc, but not age or gender, was a significant predictor of hypoglycaemia-induced QTc prolongation (p=0.001).
  
  
  CONCLUSIONS
  Insulin-induced hypoglycaemia frequently causes abnormal QT prolongation and is associated with hypokalaemia and sympathoadrenal activation, thereby increasing the potential risk for ventricular arrhythmias, particularly in individuals with pre-existing high normal QTc.
authors.affiliation: Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany. Electronic address: skacheva@ukaachen.de.
authors.forename: Stella
authors.initials: S
authors.lastname: Kacheva
authors.affiliation: Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Karges
authors.affiliation: Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Göller
authors.affiliation: Department of Cardiology, Pneumology, Angiology and Internal Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.affiliation: Department of Cardiology, Pneumology, Angiology and Internal Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mischke
authors.affiliation: Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Karges
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D061386:Insulin, Regular, Human / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D061386:Insulin, Regular, Human
keywords: Epinephrine; Insulin-induced hypoglycaemia; QT dispersion; QTc prolongation