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

Diabetologia. 2002 Jul;45(7):965-75. doi: 10.1007/s00125-002-0869-7. Epub 2002 Jun 6.


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 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.

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

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Albuminuria / drug therapy*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / urine*
  • Diastole / drug effects
  • Diuretics / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Humans
  • Male
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Posture
  • Supine Position
  • Systole / drug effects


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Diuretics
  • Metoprolol