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Diabetologia. 2002 Jul;45(7):965-75. Epub 2002 Jun 6.

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

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Medical Department M, Diabetes and Endocrinology, Kommunehospitalet, Aarhus University Hospital, Denmark.



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 beta-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional beta-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.


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.


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.


These preliminary findings indicate that beta-blocker treatment could improve autonomic function in Type I diabetic patients with abnormal albuminuria and an associated high risk of cardiovascular disease.

[Indexed for MEDLINE]

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