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

Abstract

Aims/hypothesis. The excess mortality in diabetes is mainly due to cardiovascular causes and almost confined to patients with abnormal albuminuria: Compared to healthy subjects, diabetic patients have a prolonged QT interval and increased QT dispersion. In non-diabetic subjects, as well as in Type 1 diabetic patients with overt nephropathy, a prolonged QT interval and increased QT dispersion are associated with cardiac morbidity and mortality. There is an increasing number of studies on effects of beta blocker treatment on QT interval and QT dispersion in non-diabetic subjects. In contrast, there are no studies on the effects of beta blocker treatment on QT interval and QT dispersion in patients with diabetes. The aim of our study was to describe the effects of metoprolol treatment on QT interval and QT dispersion in a group of well-characterised Type 1 diabetic patients with elevated urine albumin excretion. Methods. We studied the effects of 6 weeks of treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in a randomised, placebo-controlled, double blind, crossover trial including 20 Type 1 diabetic patients. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording and 24-h fractionated urine collections. On days of investigation 12-lead electrocardiograms were recorded and autonomic tests performed. Results. We found strong associations between both daytime and night-time blood pressure and heart-rate-corrected QT interval dispersion (QTc dispersion). Heart rate variability parameters indicating sympathetic and parasympathetic modulation showed strong correlations with heart-rate-corrected QT interval (QTc interval) and with QTc dispersion. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. Conclusions/interpretation. This study is the first to address the QTc interval and QTc dispersion in Type 1 diabetic patients treated with metoprolol. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. These results may in part explain the pronounced cardioprotective effect of beta blocker treatment in diabetic patients with cardiovascular disease.