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 ␤-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 ␤-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 ␤-blockade (3 ms, P ‫؍‬ 0.88). The increase in QTc during hypoglycemia (55 ms, P < 0.0001) was prevented by ␤-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 ␤-blockade. Diabetes

Glycemia and Corrected QT Interval Prolongation in Young Type 1 Diabetic Patients

“…Our results are in agreement with other reports that describe an abnormal repo- larization during both experimental and spontaneous clinical nocturnal hypoglycemia (7)(8)(9)17). Those data indicated that hypoglycemia can cause an acquired long QT syndrome.…”

“…The influence of changes in glycemia on the length of the QT or QTc remains a controversial issue. Experimental hypoglycemia and, just recently, spontaneous clinical episodes of hypoglycemia proved to lead to QTc lengthening (7)(8)(9). There is some evidence that prolonged cardiac repolarization contributes to sudden death associated with nocturnal hypoglycemia in young people with diabetes (10 -13).…”

Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes

“…We have previously shown that experimental hypoglycaemia is an acquired cause of abnormal cardiac repolarization with some individuals experiencing corrected QT intervals up to 580 ms [4,5]. Our data indicate that these abnormalities are caused by activation of the sympathoadrenal system since they can largely be prevented by beta blockade [6]. We have proposed that these changes might cause ventricular tachycardia and account for the increased risk of sudden overnight death in young people with The Long QT syndrome describes a variety of conditions characterised by a lengthened QT interval on the surface ECG reflecting abnormal cardiac repolarization.…”

Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes

“…Epinephrine infusion prolongs the QTc in normal subjects independently of changes in potassium levels [39]. Experimental hypoglycaemia induced by insulin infusion prolongs cardiac repolarisation in both non-diabetic and diabetic subjects [40,41,42], and this appears to be mediated by sympathoadrenal stimulation acting directly on the myocardium and by decreasing circulating potassium levels [43]. However, the design of these experiments may produce unusually high sympathoadrenal activation.…”