Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment

Abstract

Cardiac autonomic neuropathy (CAN) is a frequent chronic complication of diabetes mellitus with potentially life-threatening outcomes. CAN is caused by the impairment of the autonomic nerve fibers regulating heart rate, cardiac output, myocardial contractility, cardiac electrophysiology and blood vessel constriction and dilatation. It causes a wide range of cardiac disorders, including resting tachycardia, arrhythmias, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction and increased rate of mortality after myocardial infarction. Etiological factors associated with autonomic neuropathy include insufficient glycemic control, a longer period since the onset of diabetes, increased age, female sex and greater body mass index. The most commonly used methods for the diagnosis of CAN are based upon the assessment of heart rate variability (the physiological variation in the time interval between heartbeats), as it is one of the first findings in both clinically asymptomatic and symptomatic patients. Clinical symptoms associated with CAN generally occur late in the disease process and include early fatigue and exhaustion during exercise, orthostatic hypotension, dizziness, presyncope and syncope. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Medical therapies, including aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, prostoglandin analogs and alpha-lipoic acid, have been found to be effective in randomized controlled trials. The following article includes the epidemiology, clinical findings and cardiovascular consequences, diagnosis, and approaches to prevention and treatment of CAN.

Keywords: Diabetes mellitus; Autonomic neuropathy; Heart rate variability; Cardiac; Cardiovascular reflex tests

Core tip: Although very frequent, cardiac autonomic neuropathy (CAN) is one of the most commonly overlooked complication of diabetes. Higher incidence of cardiovascular events is encountered with CAN due to its relation with silent myocardial ischemia, arrhythmias, intraoperative cardiovascular instability, orthostatic hypotension and cardiomyopathy. Diabetic patients should be screened for CAN due to the possibility of reversal of cardiovascular denervation in the early stages of the disease. Cardiovascular reflex tests and Holter-derived time- and frequency-domain measurements are frequently used for the diagnosis. Therapeutic approaches are promising and may hinder or reverse the progression of the disease when initiated during the early stages.