Diabetes also changes the heart

Type 2 diabetes affects the energy balance and structure of heart muscle cells

Deadly double disease: Doctors have discovered that type 2 diabetes also changes the structure of heart tissue and the energy balance of heart cells. In affected patients, the heart can contract less effectively and pump less blood. This limits cardiac performance and can worsen existing heart failure, as the researchers report. Their findings explain why people with diabetes have a higher risk of heart failure.

Patients with diabetes and heart failure have a particularly high risk of death. pixabay

Heart failure and type 2 diabetes are among the most common diseases. They often occur simultaneously. However, whether and how these two diseases influence each other has been insufficiently researched so far. It is known that diabetes exacerbates the symptoms of heart disease and increases the likelihood of heart failure. But why?

Donor hearts under the microscope

Researchers led by Benjamin Hunter from the University of Sydney have now examined this in more detail. To do this, they compared the donated hearts of 20 deceased patients who did not have heart disease and the removed diseased hearts of 57 patients who had received a donor heart transplant. The patients with heart failure included both diabetics and non-diabetics.

The researchers suspect that the two diseases could be linked – for example, through the energy balance of the cells. "Under healthy conditions, the heart primarily uses fats, but also glucose and ketones, as fuel for energy production," explains Hunter. In cases of heart muscle weakness and insufficiency, the heart requires particularly high levels of energy and therefore absorbs more glucose. In diabetes, however, less glucose is available to the heart muscle cells because the transport proteins that pump glucose into the cells function less effectively.

Altered Tissue Structure of the Heart

Hunter and his colleagues therefore investigated whether traces of such a deficiency could be found in the hearts of diabetics. Indeed, a look under the microscope revealed that the heart muscle in diabetics was deformed and structurally altered. "We were able to detect direct changes in the heart muscle in the form of an accumulation of fibrous tissue," reports Hunter.

In addition to this hardened fibrous tissue, the individual heart muscle cells exhibited fewer structural proteins and calcium-binding proteins. As a result of these changes, the heart is less able to contract and pump less blood. Systolic cardiac output, in particular, is weakened, as the researchers explain.

Overview of experimental design, workflow summary, and sample summary. Workflow overview. Created with BioRender.com. (Souce:Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy / 4 August 2025 / EMBO Molicular Medicine)

Disturbed Energy Balance of Mitochondria

In extensive molecular analyses, the team identified further effects of diabetes on heart function. For example, they detected various metabolic molecules in the heart muscle cells of non-diabetics that were either greatly reduced or excessively present in diabetics. "We have long seen a link between heart disease and type 2 diabetes, but this study shows for the first time that people with both diseases have a unique molecular profile," says Hunter.

This pattern indicates profound alterations in the energy metabolism of mitochondria, the powerhouses of the cells. According to the study, the mitochondria in the heart muscle cells of diabetics are under severe strain and stress because they receive too little glucose, ketones, and fat to perform their functions. While they can rely on short fatty acids, they cannot adequately compensate for the comprehensive nutrient deficiency. The researchers conclude that the observed structural changes in the heart muscle could be a consequence of this energy deficiency.

Hope for new therapeutic approaches

Taken together, the analyses demonstrate that the heart muscle cells of diabetics lack the strength and equipment to keep the heart beating normally. This explains why diabetes impairs heart muscle function, can worsen existing disease, and can actively contribute to heart failure.

"Our research links heart disease and diabetes in a way that has never been demonstrated in humans," says senior author Sean Lal of the University of Sydney. "This gives us new clues to potential treatment strategies that could one day benefit millions of people." Knowing that diabetes alters the energy balance and structure of heart cells, researchers can now specifically test new treatments.

Furthermore, the identified molecular pattern could serve as a diagnostic marker for diabetes in heart patients.

(EMBO Molecular Medicine, 2025; doi: 10.1038/s44321-025-00281-9)

Source: University of Sydney