Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Cardiovascular disease represents the leading cause of death in people with diabetes, most notably from macrovascular diseases such as myocardial infarction or heart failure. Diabetes also increases the risk of a specific form of cardiomyopathy referred to as diabetic cardiomyopathy (DbCM), originally defined as ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. Herein, we provide an overview on the key mediators of DbCM, with an emphasis on the role for perturbations in cardiac substrate metabolism. We discuss key mechanisms regulating metabolic dysfunction in DbCM, with additional focus on the role of metabolites as signalling molecules within the diabetic heart. Furthermore, we discuss the preclinical approaches to target these perturbations to alleviate DbCM. With several advancements in our understanding, we propose "diastolic dysfunction in the presence of altered myocardial metabolism in a person with diabetes, but absence of other known causes of cardiomyopathy and/or hypertension", as a new definition for, or approach to classify, DbCM. However, we recognize that no definition can fully explain the complexity of why some individuals with DbCM exhibit diastolic dysfunction, whereas others develop systolic dysfunction. Due to DbCM sharing pathological features with heart failure with preserved ejection fraction (HFpEF), the latter of which is more prevalent in the diabetic population, it is imperative to determine whether effective management of DbCM decreases HFpEF prevalence.

Original publication




Journal article



Publication Date