Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Diabetes. Feb 15, 2014; 5(1): 17-39
Published online Feb 15, 2014. doi: 10.4239/wjd.v5.i1.17
Cardiac autonomic neuropathy in patients with diabetes mellitus
Gerasimos Dimitropoulos, Abd A Tahrani, Martin J Stevens
Gerasimos Dimitropoulos, Abd A Tahrani, Martin J Stevens, Department of Diabetes and Endocrinology, Heart of England National Health Service Foundation Trust, B15 2TT Birmingham, United Kingdom
Abd A Tahrani, Martin J Stevens, Centre of Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, B15 2TT Birmingham, United Kingdom
Author contributions: Dimitropoulos G and Tahrani AA contributed equally to this work and performed the literature search and wrote first draft; Stevens MJ provided expert opinion and reviewed the paper.
Correspondence to: Dr. Abd A Tahrani, Centre of Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, B15 2TT Birmingham, United Kingdom.
Telephone: +44-780-1549960
Received: October 15, 2013
Revised: December 2, 2013
Accepted: December 12, 2013
Published online: February 15, 2014

Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.

Keywords: Diabetes mellitus, Cardiac, Cardiovascular, Autonomic, Neuropathy, Dysfunction, Cardiac autonomic neuropathy, Sympathetic, Parasympathetic, Heart rate variability, Spectral analysis, Diabetic cardiomyopathy, Postural hypotension

Core tip: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus that is often under-diagnosed but can lead to severe morbidity and mortality, due to the associated cardiovascular burden. New evidence has emerged surrounding its complex pathways, but its full pathogenesis is yet to be understood. CAN manifests in a spectrum of subclinical and clinical presentations, ranging from resting tachycardia to cardiomyopathy. Heart rate variability and scintigraphy have enabled the diagnosis at a subclinical stage, thus providing the opportunity for better prevention and treatment. However, no definite therapeutic approaches have been adopted to date, emphasizing the need for newer targeted treatments.