Insulin prolongs the QTc interval in humans

Insulin hyperpolarizes plasma membranes; we tested whether insulin affects ventricular repolarization. In 35 healthy volunteers, we measured the Q-T i nterval 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 w as 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 pro mptly 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 ser um 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 res ting nor clamp-induced QTc was related to insulin sensitivity. Physiologica l hyperinsulinemia acutely prolongs ventricular repolarization independent of insulin sensitivity. Both insulin-induced hypokalemia and adrenergic act ivation contribute to this effect.