title: Insulin prolongs the QTc interval in humans.
abstract: Insulin hyperpolarizes plasma membranes; we tested whether insulin affects ventricular repolarization. In 35 healthy volunteers, we measured the Q-T interval during electrocardiographic monitoring in the resting state and in response to hyperinsulinemia (euglycemic 1-mU. min(-1). kg(-1) insulin clamp). A computerized algorithm was used to identify T waves; Bazett's formula was employed to correct Q-T (QTc) by heart rate (HR). In the resting state, QTc was inversely related to indexes of body size (e.g., body surface area, r = -0.53, P = 0.001) but not to indexes of body fatness. During the clamp, HR (67 +/- 1 to 71 +/- 1 beats/min, P < 0.0001) and plasma norepinephrine levels (161 +/- 12 to 184 +/- 10 pg/ml, P < 0.001) increased. QTc rose promptly and consistently, averaging 428 +/- 6 ms between 30 and 100 min (P = 0.014 vs. the resting value of 420 +/- 5 ms). Fasting serum potassium (3.76 +/- 0.03 mM) declined to 3. 44 +/- 0.03 mM during insulin. After adjustment for body size, resting QTc was directly related to fasting plasma insulin (partial r = 0.43, P = 0.01); furthermore, QTc was inversely related to serum potassium levels both in the fasting state (partial r = -0.16, P < 0. 04) and during insulin stimulation (partial r = -0.47, P = 0.003). Neither resting nor clamp-induced QTc was related to insulin sensitivity. Physiological hyperinsulinemia acutely prolongs ventricular repolarization independent of insulin sensitivity. Both insulin-induced hypokalemia and adrenergic activation contribute to this effect.
authors.affiliation: Metabolism Unit and Coronary Division, Consiglio Nazionale delle Ricerche Institute of Clinical Physiology, Department of Internal Medicine, University of Pisa School of Medicine, 56126 Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: M
authors.initials: M
authors.lastname: Emdin
authors.forename: F
authors.initials: F
authors.lastname: Conforti
authors.forename: S
authors.initials: S
authors.lastname: Camastra
authors.forename: E
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011188:Potassium