Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2015; 6(1): 80-91
Published online Feb 15, 2015. doi: 10.4239/wjd.v6.i1.80
Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment
Akif Serhat Balcıoğlu, Haldun Müderrisoğlu
Akif Serhat Balcıoğlu, Medical and Research Center of Alanya, Department of Cardiology, Başkent University, 07400 Alanya, Antalya, Turkey
Haldun Müderrisoğlu, Faculty of Medicine, Department of Cardiology, Başkent University, 06490 Ankara, Turkey
Author contributions: Balcıoğlu AS performed the literature search and wrote the paper; Müderrisoğlu H provided expert opinion and reviewed the article.
Conflict-of-interest: The authors confirm that the manuscript has no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Akif Serhat Balcıoğlu, MD, Medical and Research Center of Alanya, Department of Cardiology, Başkent University, Saray Mahallesi, Yunus Emre Caddesi, No: 1, 07400 Alanya, Antalya, Turkey.
Telephone: +90-242-5102525 Fax: +90-242-5115563
Received: August 22, 2014
Peer-review started: August 23, 2014
First decision: September 19, 2014
Revised: November 16, 2014
Accepted: November 27, 2014
Article in press: December 1, 2014
Published online: February 15, 2015

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.