Diabetic Cardiovascular Autonomic Neuropathy: How to Detect This Serious Diagnosis and Why Is It Dangerous?

Why is it important to consider it?

Diabetic cardiovascular autonomic neuropathy (CAN) increases morbidity and mortality in diabetics and demonstrably reduces their quality of life. Ziegler et al. already in 1994 demonstrated that 29% of diabetics afflicted with a severe form of CAN died within 10 years, compared to 6% without CAN. Subsequent studies by these and other authors confirmed the significant increase in mortality in patients with CAN. Additionally, diabetics with CAN have a 2 to 3 times higher cardiovascular perioperative risk.

Clinical manifestations

CAN involves abnormalities in the control of heart rate and central and peripheral vascular dynamics. Potential symptoms that may alert us to CAN include:

Resting Tachycardia

This is a fixed tachycardia with no response to changes in physical exertion, sleep, or stress. The heart rate typically hovers around 100/min, and patients may not be aware of it.

Postural Hypotension

For diagnosis, a significant drop in systolic blood pressure by more than 30 mmHg after transitioning to an upright position is notable. Characteristic manifestations include:

• weakness, sometimes syncope after standing up
• vertigo
• vision impairment

In differential diagnosis, it is necessary to consider hypoglycemia and side effects of medications, especially diuretics, vasodilators, and tricyclic antidepressants.

Exercise Intolerance

Patients experience reduced capacity for tolerated exertion. The same symptoms can occur with ischemic heart disease.

Left Ventricular Dysfunction

Both systolic and diastolic dysfunction of the left ventricle occur, even without the presence of ischemic heart disease. Ventricular dysfunction in diabetic patients not due to coronary artery sclerosis and hypertension is termed diabetic cardiomyopathy.

Heat Intolerance, Edema

Possible manifestations of CAN also include heat intolerance and impaired venoarterial reflex leading to edema.

Significant association with kidney disease

A connection between CAN and diabetic kidney disease, albuminuria, and reduced renal function has been demonstrated. Ewing et al. found up to a 53% increase in mortality in diabetic patients with autonomic neuropathy compared to a 15% increase in mortality in diabetics without autonomic neuropathy. Half of all deaths in diabetics with autonomic neuropathy occurred due to worsening kidney function.

Causes of death in diabetics with CAN

The most common causes of death in diabetics with CAN include:

• myocardial infarction
• stroke
• sudden death

In cases of sudden death, disturbances in the variability of the RR interval, prolongation of the QT interval, and often hypertension are observed. Sudden death referred to as death in bed syndrome is also common. Its probable cause is hypoglycemia, which may not be severe but induces malignant arrhythmia through sympathetic activation.

Diagnosis and treatment

The frequent absence of clear symptoms makes diagnosis challenging. In medical history, we specifically inquire about palpitations, fainting, or dizziness after standing up. Resting tachycardia over 100/min and a significant orthostatic test should raise suspicion. To confirm the diagnosis, analyses of heart rate variability over time and spectral analysis are commonly used today, and nuclear medicine methods can also be utilized. Treatment of CAN, besides improving diabetes control, is primarily symptomatic.

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Sources:
1. Pecoits-Filho R., Abensur H., Betônico C. C. et al. Interactions between kidney disease and diabetes: dangerous liaisons. Diabetol Metab Syndr 2016; 8: 50, doi: 10.1186/s13098-016-0159-z.
2. Adamíková A., Bakala J. Autonomic neuropathy and heart involvement in diabetes. Internal Medicine 2012; 14 (1): 18–20. 
3. Lacigová S., Tomešová J., Gruberová J. Diabetic autonomic neuropathy. Neurology for Practice 2012; 13 (Suppl. E): E16–E19.
4. Ziegler D. Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev 1994; 10 (4): 339–383, doi: 10.1002/dmr.5610100403. 
5. Ewing D. J., Campbell I. W., Clarke B. F. The natural history of diabetic autonomic neuropathy. Q J Med 1980; 49 (193): 95–108.