Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2019; 10(10): 490-510
Published online Oct 15, 2019. doi: 10.4239/wjd.v10.i10.490
Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date
Lavanya Athithan, Gaurav S Gulsin, Gerald P McCann, Eylem Levelt
Lavanya Athithan, Gaurav S Gulsin, Gerald P McCann, Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester LE3 9QP, United Kingdom
Eylem Levelt, Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LF9 7TF, United Kingdom
Author contributions: Athithan L performed the literature review and wrote the draft of the paper and Gulsin GS also contributed to the writing and editing of the manuscript which was critically revised and edited by Levelt E and McCann GP. All authors approved the final version.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This is an open-access article that 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lavanya Athithan, MBChB, MRCP, Doctor, Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Groby road, Leicester LE3 9QP, United Kingdom. la185@leicester.ac.uk
Telephone: +44-116-2583285
Received: May 14, 2019
Peer-review started: May 20, 2019
First decision: May 31, 2019
Revised: September 25, 2019
Accepted: September 25, 2019
Article in press: September 25, 2019
Published online: October 15, 2019
Abstract

The prevalence of type 2 diabetes (T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms, with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.

Keywords: Diabetic cardiomyopathy, Cardiac metabolism, Myocardial steatosis, Myocardial strain

Core tip: Altered myocardial metabolism and impaired metabolic flexibility are key mechanisms implicated in diabetic cardiomyopathy. Glucotoxicity, lipotoxicity, coronary microvascular dysfunction and suboptimal substrate utilisation are examined in detail. The mechanisms implicated and the impact on myocardial structure and function have been scrutinised within this review.