Diabetic Cardiomyopathy and Cardiac Metabolism

Diabetic cardiomyopathy describes a distinct myocardial dysfunction arising in the context of diabetes, independent of coronary artery disease or hypertension. Chronic hyperglycaemia and insulin resistance induce shifts in cardiac substrate utilisation, with enhanced reliance on fatty acid oxidation and suppressed glucose oxidation. This metabolic inflexibility leads to inefficient adenosine triphosphate (ATP) production, increased oxygen consumption, and accumulation of toxic lipid intermediates. Excessive generation of reactive oxygen species and pro-inflammatory signalling promote cardiomyocyte apoptosis, interstitial fibrosis and remodelling of the extracellular matrix, resulting in impaired contractility and diastolic dysfunction. Early detection through advanced imaging and metabolic profiling offers the prospect of targeted intervention. Therapeutic strategies that restore metabolic balance, mitigate oxidative stress and enhance myocardial energy efficiency hold promise for reducing the global burden of diabetic heart failure.

Research from Nature Portfolio

Recent studies have delineated a regulatory axis orchestrating the balance between glycolysis and fatty acid oxidation in the diabetic heart. One investigation demonstrated that the transcription factor KLF7 directly regulates both phosphofructokinase-1 and long-chain acyl-CoA dehydrogenase, thereby modulating glycolytic flux and mitochondrial fatty acid utilisation. Manipulation of this pathway in animal models reversed pathological hypertrophy and improved cardiac performance, suggesting that fine-tuning of metabolic enzymes may offer a novel approach to counteract energy inefficiency in diabetic cardiomyopathy.

Diabetic Cardiomyopathy and Cardiac Metabolism publication trend

The graph below shows the total number of articles in diabetic cardiomyopathy and cardiac metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

Diabetic cardiomyopathy: A form of heart muscle disease characterised by ventricular dysfunction in diabetic patients, independent of other cardiac risk factors.

Metabolic flexibility: The capacity of the myocardium to switch between energy substrates such as fatty acids, glucose and ketones in response to physiological demands.

Glycolysis: The enzymatic breakdown of glucose to pyruvate, yielding ATP and NADH in the cytosol.

Fatty acid oxidation: The mitochondrial process by which long-chain fatty acids are converted to acetyl-CoA for ATP generation via oxidative phosphorylation.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that, in excess, cause oxidative damage to proteins, lipids and DNA.

Extracellular matrix: The network of proteins and glycoproteins that provides structural support and regulates cellular signalling within cardiac tissue.

References

1. The KLF7/PFKL/ACADL axis modulates cardiac metabolic remodelling during cardiac hypertrophy in male mice. Nature Communications (2023).
2. Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1‐Foxo1 and PI3K‐Akt signalling pathways. Journal of Cellular and Molecular Medicine (2020).
3. Mitochondrial ROS Formation in the Pathogenesis of Diabetic Cardiomyopathy. Frontiers in Cardiovascular Medicine (2020).
4. Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization. Journal of Lipid Research (2018).
5. Diagnostic approaches for diabetic cardiomyopathy. Cardiovascular Diabetology (2017).
6. Loss of Metabolic Flexibility in the Failing Heart. Frontiers in Cardiovascular Medicine (2018).
7. Diabetic cardiomyopathy: pathophysiology and clinical features. Heart Failure Reviews (2012).
8. Diabetic Cardiovascular Disease Induced by Oxidative Stress. International Journal of Molecular Sciences (2015).
9. Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control. Frontiers in Physiology (2018).