From Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Victoria, Australia (R.H.R.).
Division of Endocrinology and Metabolism (E.D.A.), University of Iowa Carver College of Medicine, Iowa City.
Circ Res. 2020 May 22;126(11):1501-1525. doi: 10.1161/CIRCRESAHA.120.315913. Epub 2020 May 21.
Diabetes mellitus predisposes affected individuals to a significant spectrum of cardiovascular complications, one of the most debilitating in terms of prognosis is heart failure. Indeed, the increasing global prevalence of diabetes mellitus and an aging population has given rise to an epidemic of diabetes mellitus-induced heart failure. Despite the significant research attention this phenomenon, termed diabetic cardiomyopathy, has received over several decades, understanding of the full spectrum of potential contributing mechanisms, and their relative contribution to this heart failure phenotype in the specific context of diabetes mellitus, has not yet been fully resolved. Key recent preclinical discoveries that comprise the current state-of-the-art understanding of the basic mechanisms of the complex phenotype, that is, the diabetic heart, form the basis of this review. Abnormalities in each of cardiac metabolism, physiological and pathophysiological signaling, and the mitochondrial compartment, in addition to oxidative stress, inflammation, myocardial cell death pathways, and neurohumoral mechanisms, are addressed. Further, the interactions between each of these contributing mechanisms and how they align to the functional, morphological, and structural impairments that characterize the diabetic heart are considered in light of the clinical context: from the disease burden, its current management in the clinic, and where the knowledge gaps remain. The need for continued interrogation of these mechanisms (both known and those yet to be identified) is essential to not only decipher the how and why of diabetes mellitus-induced heart failure but also to facilitate improved inroads into the clinical management of this pervasive clinical challenge.
糖尿病使受影响的个体易患广泛的心血管并发症，就预后而言，心力衰竭是最具危害性的并发症之一。事实上，由于全球糖尿病患病率的增加和人口老龄化，导致了糖尿病性心力衰竭的流行。尽管几十年来，人们对这种被称为糖尿病心肌病的现象给予了极大的关注，但对于潜在的潜在机制的全貌，以及它们在糖尿病的具体背景下对这种心力衰竭表型的相对贡献，尚未得到充分解决。最近的一些关键的临床前发现，构成了对复杂表型（即糖尿病心脏）基本机制的当前最先进的理解，是本综述的基础。本文讨论了心脏代谢、生理和病理生理信号以及线粒体区室的异常，以及氧化应激、炎症、心肌细胞死亡途径和神经激素机制。此外，还考虑了这些致病机制之间的相互作用，以及它们如何与糖尿病心脏的功能、形态和结构损伤相吻合，这些损伤是基于临床背景的：从疾病负担、其目前在临床上的管理，以及知识空白仍然存在的地方。继续研究这些机制（已知的和尚未确定的）是至关重要的，不仅要阐明糖尿病引起心力衰竭的机制，还要促进对这一普遍临床挑战的临床管理的改进。
