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J Intern Med. 2000 Dec;248(6):483-91.

Cardiovascular autonomic neuropathy in insulin-dependent diabetes mellitus: prevalence and estimated risk of coronary heart disease in the general population.

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Department of Cardiology, Odense University Hospital, Odense, Denmark.



The aim of the study was to estimate the prevalence of cardiovascular autonomic neuropathy (CAN) in Type 1 diabetes mellitus in the general population and to assess the relationship between CAN and risk of future coronary heart disease (CHD).


The Type 1 diabetes mellitus population in the municipality of Horsens, Denmark, was delineated by the prescription method and a random sample of 120 diabetics aged 40-75 years was recruited. Type 1 diabetes mellitus was registered if fasting C-peptide was below 0.30 nmol L(-1). The E/I ratio was calculated as the mean of the longest R-R interval in expiration divided by the shortest in inspiration during deep breathing at 6 breaths min(-1) and taken to express the degree of CAN. A maximal symptom-limited exercise test was carried out and the VA Prognostic Score, indicating risk of cardiovascular death or non-fatal myocardial infarction, was computed. Additionally, the 10-year risk of CHD was calculated using the Framingham model.


A total of 84 people responded, of whom 71 had Type 1 diabetes mellitus. The E/I ratio was measured in 69 people. The prevalence of CAN expressed as an E/I ratio below the normal 5th percentile was 38%. The E/I ratio was significantly reduced in old age, long duration of diabetes, female gender, high fasting blood glucose, triglyceride, systolic blood pressure and urinary albumin excretion. A high risk of future CHD calculated using the Framingham model was associated with a low E/I ratio (r = -0.39, P = 0.001). Exercise capacity, rise in systolic blood pressure and heart rate were positively correlated with the E/I ratio. A high VA Prognostic Score was correlated with a low E/I ratio (r = - 0.58, P < 0.0005). The risks estimated by the two models were significantly correlated (r = 0.60, P < 0.0005).


The prevalence of CAN in the 40-75-year-old Type 1 diabetes mellitus population is estimated to be 38%. CAN is associated with exercise test parameters and a coronary risk factor profile indicating a high risk of future CHD.

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