Researchers at the University of Sydney have discovered that type 2 diabetes directly alters the heart's structure and energy production, increasing the risk of heart failure. By examining donated human heart tissue, the team identified molecular changes that stiffen the muscle and disrupt cellular function. These findings, published in EMBO Molecular Medicine, highlight a unique profile in patients with both diabetes and ischemic heart disease.
A new study led by Dr. Benjamin Hunter and Associate Professor Sean Lal at the University of Sydney reveals how type 2 diabetes physically transforms the human heart. Published in EMBO Molecular Medicine in 2025, the research analyzed heart tissue from transplant recipients in Sydney and healthy donors. The findings show that diabetes interferes with energy production in heart cells, reduces insulin sensitivity in glucose transporters, and stresses mitochondria, the cell's energy producers.
In patients with ischemic cardiomyopathy—the leading cause of heart failure—these effects are amplified. Diabetes lowers levels of proteins essential for muscle contraction and calcium regulation, while promoting fibrosis, or fibrous tissue buildup, which stiffens the heart and impairs pumping efficiency. Advanced techniques like RNA sequencing and confocal microscopy confirmed these changes at both molecular and structural levels.
"We've long seen a correlation between heart disease and type 2 diabetes," Dr. Hunter noted, "but this is the first research to jointly look at diabetes and ischemic heart disease and uncover a unique molecular profile in people with both conditions."
The study underscores that diabetes actively accelerates heart failure beyond being a risk factor. In Australia, where heart disease is the top killer and over 1.2 million people live with type 2 diabetes, these insights could shape future diagnostics and treatments. Associate Professor Lal emphasized: "Our research links heart disease and diabetes in ways that have never been demonstrated in humans, offering new insights into potential treatment strategies that could one day benefit millions."
By focusing on human tissue rather than animal models, the work provides direct evidence of diabetes's impact, paving the way for targeted therapies addressing mitochondrial dysfunction and fibrosis.
