Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria

Aims/hypothesis. Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In non-diabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that β-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional β-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria. Methods. We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out. Results. Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in daytime diastolic blood pressure was shown, no alterations in diurnal variation of blood pressure or urine albumin excretion were observed. Conclusion/interpretation. These preliminary findings indicate that β-blocker treatment could improve autonomic function in Type I diabetic patients with abnormal albuminuria and an associated high risk of cardiovascular disease.