Diabetes changes the structure of our hearts, study finds

Researchers from The University of Sydney have revealed that type 2 diabetes directly alters the heart’s structure and energy systems, offering insights into why people with diabetes are at greater risk of heart failure. Their work has been published in the journal EMBO Molecular Medicine.

Led by Dr Benjamin Hunter and Associate Professor Sean Lal, the research team analysed donated human heart tissue from both transplant recipients and healthy donors. They found that diabetes causes distinct molecular changes to heart cells and structural changes to the muscle — especially in patients with ischaemic cardiomyopathy, the most common cause of heart failure.

This means that diabetes is not just a co-morbidity for heart disease — it actively worsens heart failure by disrupting key biological processes and reshapes the heart muscle at a microscopic level.

“We’ve long seen a correlation between heart disease and type 2 diabetes, but this is the first research to jointly look at diabetes and ischaemic heart disease and uncover a unique molecular profile in people with both conditions,” said Hunter, who noted that the metabolic effect of diabetes in the heart is not fully understood in humans.

“Under healthy conditions, the heart primarily uses fats but also glucose and ketones as fuel for energy,” Hunter continued. “It has previously been described that glucose uptake is increased in heart failure; however, diabetes reduces the insulin sensitivity of glucose transporters — proteins that move glucose in and out of cells — in heart muscle cells.

“We observed that diabetes worsens the molecular characteristics of heart failure in patients with advanced heart disease and increases the stress on mitochondria — the powerhouse of the cell, which produces energy.”

The researchers also observed reduced production of structural proteins critical for heart muscle contraction and calcium handling in people with diabetes and ischaemic heart disease, along with a build-up of tough, fibrous heart tissue that further affects the heart’s ability to pump blood.

“RNA sequencing confirmed that many of these protein changes were also reflected at the gene transcription level, particularly in pathways related to energy metabolism and tissue structure, which reinforces our other observations,” Hunter said.

“And once we had these clues at the molecular level, we were able to confirm these structural changes using confocal microscopy.”

According to Lal, the discovery of mitochondrial dysfunction and fibrotic pathways could help guide future therapies.

“Now that we’ve linked diabetes and heart disease at the molecular level and observed how it changes energy production in the heart while also changing its structure, we can begin to explore new treatment avenues,” he said.

“Our findings could also be used to inform diagnosis criteria and disease management strategies across cardiology and endocrinology, improving care for millions of patients.”

Image credit: iStock.com/ArLawKa AungTun