Project summary
People living with type 2 diabetes have a higher risk of developing serious heart and blood vessel problems. Growing evidence suggests this may in part be driven by long‑lasting inflammation in the body, but we don’t know what triggers this.
Professor Squires and his PhD student will investigate whether substances produced by gut bacteria could be the missing link, offering new clues into the development of cardiovascular complications and how to stop them.
Background to research
People living with type 2 diabetes have a higher risk of heart and blood vessel disease (cardiovascular disease). Current care helps people lower their risk by managing blood sugar levels, cholesterol, and blood pressure. But treatments don’t address another factor that scientists think can drive cardiovascular damage: long‑lasting, low‑level inflammation.
The gut may play an important role in this persistent inflammation. The gut is home to trillions of bacteria. When the mix of gut bacteria is unbalanced, some bacteria can release harmful substances that enter the bloodstream and affect other organs. One of these substances, imidazole propionate (ImP), is found at higher levels in people with type 2 diabetes.
Early evidence suggests ImP may act like a trigger, it can stress blood vessels and immune cells in a way that turns on inflammation.
Professor Paul Squires and his PhD students will investigate these processes further.
Research aims
Professor Squires and his student will investigate how ImP affects the cardiovascular system by studying human cell grown in the lab.
First, the team will study how how ImP influences immune cells called macrophages, which play a central role in inflammation. They’ll examine whether ImP switches on inflammatory pathways that are known to contribute to diabetes‑related cardiovascular complications.
Next, they will investigate how ImP affects endothelial cells, which line the inside of blood vessels. The team will look for early signs of blood‑vessel damage, such as leakiness.
Finally, the researchers will expose the cells to blood samples taken from people with type 2 diabetes and heart disease, taken before and after treatment with commonly used diabetes and heart medicines. This will help show whether these existing medications may reduce the harmful effects triggered by ImP.
Potential benefit to people with diabetes
There are millions of people living with type 2 diabetes, and heart‑related complications remain far too common. While current treatments are effective at controlling many risk factors, they do not address them all cardiovascular disease.
By uncovering how gut-driven inflammation drives heart damage in type 2, it could point to new treatment options or new uses for existing drugs. This could help prevent devastating complications for people living with type 2 diabetes and save lives.
