Basic Mechanisms of Diabetic Heart Disease.
Authors Ritchie RH, Abel ED
Submitted By Submitted Externally on 6/8/2020
Status Published
Journal Circulation research
Year 2020
Date Published 5/1/2020
Volume : Pages 126 : 1501 - 1525
PubMed Reference 32437308
Abstract 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.