Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus?

The appearance of microalbuminuria in diabetic patients predicts development of macroalbuminuria and coronary heart disease. Autonomic dysfunction in ischaemic heart disease is related to an increased incidence of arrhythmic deaths. To assess sympathovagal balance in relation to microalbuminuria we performed 24-h spectral analysis of RR interval oscillations in 37 insulin-dependent diabetic patients. Patients were divided according to urinary albumin excretion as normo-(< 20 micrograms/min) (n = 12), micro-(> 20 and < 200 micrograms/min) (n = 14) and macro-albuminuria (> 200 micrograms/min) (n = 11). None had symptoms or signs of ischaemic heart disease at clinical examination or during stress testing. Fourteen matched healthy subjects served as controls. Overall RR interval variability was calculated as the 24-h standard deviation. The square root of power of the low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.40 Hz) component were considered indices of the sympathovagal interaction and vagal function, respectively. Patients with micro and macroalbuminuria had, compared to control subjects, significantly reduced 24-h standard deviation, a much smaller day/night difference in mean RR level and a significantly reduced amplitude of the low frequency and high frequency oscillations, which were even more reduced in macroalbuminuria. The differences in vagal function were also present after correction for mean RR level, and differences in physical training level and smoking. Insulin-dependent diabetic patients who develop microalbuminuria have significantly impaired vagal function and abnormal sympathovagal interaction, which is further deranged in macroalbuminuria. This early autonomic dysfunction may later contribute to a increased risk for sudden cardiac death.