Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation
Abstract
Type 2 diabetes is a highly prevalent metabolic disease that significantly impacts the heart and contributes to an increased risk of cardiac complications, notably heart failure with preserved ejection fraction and cardiac arrhythmias, which can cause sudden cardiac death. In type 2 diabetes chronic hyperglycaemia and insulin resistance lead to subcellular changes, including dysregulation of calcium/calmodulin-dependent protein kinase II (CaMKII), intracellular sodium and calcium handling and potassium currents, all of which impair cardiac contractility and repolarisation. Type 2 diabetes induces diffuse myocardial fibrosis and anatomical remodelling, which contribute to diastolic and systolic dysfunction, and the formation of a pro-arrhythmic substrate. Impaired connexin 43-mediated conduction and cardiac autonomic neuropathy further promote cardiac electrophysiological and mechanical dysfunction. Clinical studies using the ECG and cardiac imaging modalities have been successful in detecting some of these changes; however our mechanistic understanding of type 2 diabetes-driven cardiac disorders remains limited. Recent advances in multiscale computational modelling and simulation of human cardiac electrophysiology and mechanics provide new opportunities to study diabetes-induced cardiac remodelling in silico by unravelling disease mechanisms across different scales and assisting in the development of novel therapies. Here we review key pathophysiological mechanisms of…
How strong is the evidence?
Evidence Hub reads this as a review, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.