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Diabetes Res Clin Pract. 1998 Oct;42(1):55-63.

The natural history of recently diagnosed autonomic neuropathy over a period of 2 years.

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  • 1Diabetes Center, 2nd Propedeutic Department of Internal Medicine, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece.



Patients with diabetic autonomic neuropathy (DAN) have an increased cardiovascular mortality rate compared with normals or diabetic patients without DAN. Indices of standard cardiovascular autonomic function tests and heart rate variability (HRV) are reliable markers of the presence and severity of DAN.


The present prospective study investigated the natural history of values of HRV indices and cardiovascular reflex tests in patients with recently diagnosed asymptomatic DAN, over a period of 2 years, at 3 month intervals.


A total of 30 consecutive patients (nine men and 21 women), of median age 51 (range 25-65) years, eight with type 1 and 22 with Type 2 diabetes mellitus, were included in the study, at the time that the presence of DAN was confirmed, as this was established if at least two of cardiovascular autonomic function tests became abnormal. The expiration/inspiration (E/I) ratio. S.D. and mean circular resultant of R-R intervals, the Valsalva index, the 30:15 ratio, and the blood pressure response to standing as well as normalised spectral power indices of HRV were used.


All measured indices, except the Valsalva index, deteriorated in all 30 patients during the 2 year follow-up. Most of HRV indices values deteriorated significantly in comparison to baseline at month 12, while the values of cardiovascular reflex tests displayed significant deterioration, in comparison to baseline, between months 15 and 21. Fourteen patients developed symptoms of DAN during the 2 year period. Patients with better glycemic control exhibited deterioration of DAN markers at the same time period with those with poor glycemic control.


Our data suggest that the progression of DAN is significant during the 2 years subsequent to its discovery. This was defined by the deterioration of the mean values of HRV indices and standard cardiovascular autonomic function tests, and by the development of autonomic symptoms in some patients. HRV indices are the earlier markers of DAN deterioration.

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