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Journal article : Review

Redefining diabetic cardiomyopathy: perturbations in substrate metabolism at the heart of its pathology

Abstract:
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 signaling 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 the following as a new definition for, or approach to classify, DbCM: “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.” 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 population with diabetes, it is imperative to determine whether effective management of DbCM decreases HFpEF prevalence.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.2337/dbi23-0019

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy and Genetics
Oxford college:
Linacre College
Role:
Author
ORCID:
0000-0002-7246-1338
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy and Genetics
Role:
Author
ORCID:
0000-0003-0539-7046
More by this author
Role:
Author
ORCID:
0000-0001-9574-5707


More from this funder
Funder identifier:
https://ror.org/02wdwnk04
Grant:
FS/17/58/33072
More from this funder
Funder identifier:
https://ror.org/01gavpb45
Grant:
PJT-159648


Publisher:
American Diabetes Association
Journal:
Diabetes More from this journal
Volume:
73
Issue:
5
Pages:
659-670
Place of publication:
United States
Publication date:
2024-02-22
Acceptance date:
2024-02-15
DOI:
EISSN:
1939-327X
ISSN:
0012-1797
Pmid:
38387045


Language:
English
Keywords:
Subtype:
Review
Pubs id:
1691881
Local pid:
pubs:1691881
Deposit date:
2025-06-11

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