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.

中文翻译：

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重新定义糖尿病心肌病：其病理学核心的底物代谢扰动

心血管疾病是糖尿病患者死亡的主要原因，尤其是心肌梗塞或心力衰竭等大血管疾病。糖尿病还会增加患一种特定形式的心肌病（称为糖尿病心肌病（DbCM））的风险，最初定义为在没有潜在冠状动脉疾病和/或高血压的情况下出现心室功能障碍。在此，我们概述了 DbCM 的关键介质，重点介绍了扰动在心脏底物代谢中的作用。我们讨论了调节 DbCM 代谢功能障碍的关键机制，特别关注代谢物作为糖尿病心脏内信号分子的作用。此外，我们讨论了针对这些扰动以减轻 DbCM 的临床前方法。随着我们理解的一些进展，我们提出“糖尿病患者心肌代谢改变而出现舒张功能障碍，但不存在心肌病和/或高血压的其他已知原因”，作为新的定义或分类方法，数据库管理。然而，我们认识到，没有任何定义可以完全解释为什么一些 DbCM 患者表现出舒张功能障碍，而其他人则出现收缩功能障碍。由于 DbCM 与射血分数保留的心力衰竭 (HFpEF) 具有共同的病理特征，后者在糖尿病人群中更为常见，因此必须确定 DbCM 的有效管理是否会降低 HFpEF 的患病率。