title: Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia.
abstract: Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these contribute to sudden death associated with nocturnal hypoglycemia in young people with diabetes. We measured cardiac repolarization (QT interval [QTc] and QT dispersion [QTd]) during experimental hypoglycemia with and without beta-blockade and potassium infusion to establish possible mechanisms. Two groups of 10 nondiabetic men (study 1 and study 2) each underwent four hyperinsulinemic clamps: two euglycemic (5 mmol/l) and two hypoglycemic (5 mmol/l and 2.5 mmol/l for 60 min each). Study 1 was performed with and without potassium infusion to maintain normal concentrations and study 2 with and without beta-blockade (atenolol, 100 mg/day for 7 days). QTd was unchanged during euglycemia but increased during hypoglycemia (55 ms, P < 0.0001 vs. baseline), which was prevented by potassium (6 ms, P = 0.78). QTc increased significantly during hypoglycemia alone (67 ms, P < 0.0001) and during potassium replacement (46 ms, P = 0.02). In study 2, the increase in QTd during hypoglycemia (68 ms, P < 0.0001) was prevented by beta-blockade (3 ms, P = 0.88). The increase in QTc during hypoglycemia (55 ms, P < 0.0001) was prevented by beta-blockade (1 ms, P = 0.98). Our data indicate that hypoglycemia causes an acquired long QT syndrome. Sympathoadrenal stimulation is the main cause, through mechanisms that involve but are not limited to catecholamine-mediated hypokalemia. These abnormalities are prevented by selective beta-blockade.
authors.affiliation: Clinical Sciences Center, Northern General Hospital, University of Sheffield, Sheffield S57 AU, U.K.
authors.forename: Robert T C E
authors.initials: RT
authors.lastname: Robinson
authors.forename: Nigel D
authors.initials: ND
authors.lastname: Harris
authors.forename: Robert H
authors.initials: RH
authors.lastname: Ireland
authors.forename: Stuart
authors.initials: S
authors.lastname: Lee
authors.forename: Christopher
authors.initials: C
authors.lastname: Newman
authors.forename: Simon R
authors.initials: SR
authors.lastname: Heller
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D015309:Glucose Clamp Technique; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000097:blood / Q000494:pharmacology; D012016:Reference Values
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007328:Insulin; D001262:Atenolol; D011188:Potassium; D004837:Epinephrine