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

Abstract

Aims/hypothesis. Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. Methods. We studied 22 patients with Type 1 diabetes (mean age 40.4±17.2 years, duration of diabetes 17.2±9.3 years, HbA1c 8.2±1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. Results. Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (±15) above baseline, compared with 9 ms (±19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (±0.21) above baseline during hypoglycaemia, compared with −0.05 nmol/l (±0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. Conclusion/interpretation. QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia. [Diabetologia (2004) 47:312-315]

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

“…Conversely, other studies have reported that abnormal autonomic function at this age [33,34,35,36,37] is largely related to hyperglycaemia and elevated HbA 1 c. However, our data strongly indicate that spontaneous hypoglycaemia rather than hyperglycaemia is the more important determinant of prolonged QTc at night in type 1 diabetic children and adolescents. We have recently demonstrated similar changes during hypoglycaemia in adults [38]. We chose a glucose level of 3.5 mmol/l to define hypoglycaemia as previous studies carried out by our group in children and adolescents demonstrated that levels in normal children almost never go below this value.…”

Effects of metoprolol on QT interval and QT dispersion in Type 1 diabetic patients with abnormal albuminuria

“…Both these conditions are possibly linked to cardiac autonomic neuropathy and prolonged QT interval. In experimental and in spontaneous nocturnal hypoglycaemia, prolongation in QTc has been demonstrated [32,33], and pre-treatment with a beta blocker demonstrably prevented abnormal repolarisation during experimental hypoglycaemia [32]. We have previously shown that it is possible to improve heart rate variability parameters by B1-selective beta blockade [19].…”

Diabetic Neuropathy: A Position Statement by the American Diabetes Association

“…It was also suggested that intensification of glucose and blood pressure management may increase the risk of a cardiovascular event in people with signs of CAN (161)(162)(163)(164)(165). Similarly, emerging evidence demonstrates an association between CAN and glucose variability, especially in the hypoglycemic range (150,164).…”