Wir überwinden Grenzen

(13.1.2026) Inflammatory reaction identified as a possible cause of organ damage. A study opens up new therapeutic approaches. Published in the European Heart Journal at the end of 2025.

People with diabetes have a significantly increased risk of heart failure and kidney disease - even with well-controlled blood glucose levels. An international research team led by the Medical Center - University of Freiburg has identified a central immune mechanism that can explain these secondary diseases. The study shows that the enzyme peptidylarginine deiminase 4 (PAD4) activates certain immune cells and thus triggers inflammatory processes that damage the heart and kidneys. The results were published in the European Heart Journal on November 27, 2025.

Secondary diseases due to misdirected immune response

"Our results show for the first time that PAD4 is a central link between diabetes and inflammatory processes in the heart and kidneys," says study leader Dr. Lukas A. Heger, a specialist at the Department of Cardiology and Angiology at the Medical Center - University of Freiburg. "This misdirected immune response could explain why many patients develop severe secondary diseases despite good blood glucose control."

Evidence from patient samples and animal models

The study focuses on the enzyme PAD4, which plays a key role in the activation of immune cells. The researchers were able to show that increased glucose levels directly activate so-called neutrophil granulocytes. These immune cells then release pro-inflammatory messengers and neutrophil extracellular traps (NETs). This process is controlled by PAD4 and leads to a sustained inflammatory response that not only fights pathogens but also damages healthy tissue.

In heart tissue from patients with heart failure, the researchers found significantly more NET deposits in patients with diabetes than in patients without diabetes. The more pronounced the deposits were, the more impaired the heart function was. These observations were confirmed in animal models: Only mice with active PAD4 developed typical diabetes-related damage such as reduced cardiac output, scarring in the tissue and impaired kidney function.

New perspectives for therapy

The results show that organ damage in diabetes is not solely caused by increased blood glucose levels, but is essentially mediated by a PAD4-dependent immune response. The heart and kidneys are particularly affected.

"PAD4 acts like a switch that programs neutrophils for inflammation," said Prof. Dr. Dirk Westermann, Medical Director of the Department of Cardiology and Angiology at the Medical Center - University of Freiburg. "Targeted inhibition of this enzyme could help to prevent heart and kidney damage in diabetes in the future."

The study thus opens up new therapeutic perspectives that go beyond the mere control of blood sugar.

More interesting articles