High blood sugar levels ‘reprogram’ stem cells

High levels of glucose in the blood “reprogram” stem cells, leading to a lasting increase in the risk of developing dangerous atherosclerosis, according to research funded by the British Heart Foundation published today in Circulation.

Researchers at the University of Oxford have found that some blood glucose, a hallmark of diabetes, damages stem cells in the bone marrow that become white blood cells called macrophages. As a result, these macrophages become inflammatory and contribute to the development of atherosclerotic plaques that can cause heart attacks.

This finding explains why people with diabetes are at increased risk of heart attack even after their blood sugar has returned to control, a paradox that has worried doctors for years.

Almost five million people in the UK have diabetes, and adults with the disease are twice as likely to have a heart attack. These findings open up new possibilities for treatments that could reduce the risk of heart and circulatory disease in people with diabetes.

The team studied the differences in white blood cells in people with and without type 2 diabetes. They removed the white blood cells from blood samples and cultured them in an environment with normal glucose levels. Those of people with type 2 diabetes showed a inflammatory reaction compared to the cells of unconditional people.

The researchers also extracted the stem cells bone marrow from diabetic and non-diabetic mice and transplanted into mice blood glucose level. Bone marrow taken from diabetic mice “remembered” its exposure to high levels of glucose, and as a result, mice receiving this bone marrow developed almost double the amount of atherosclerotic plaques.

When the team took a closer look at mouse macrophages, they found that those that had developed from stem cells in the bone marrow of diabetic mice had been permanently altered to become more inflammatory.

The team now wants to explore new treatment avenues based on this discovery. They also want to know if short periods of blood sugar spikes in people without diabetes have this detrimental effect.

Professor Robin Choudhury, professor of cardiovascular medicine in the Radcliffe Department of Medicine at the University of Oxford, led the research. He said:

“Our study is the first to show that diabetes causes long-term changes in the immune system, and how this may explain the sustained increase in heart attack risk.

“We need to change the way we think about and deal with diabetes. By focusing too narrowly on managing a person’s blood sugar, we only solve part of the problem.

“Currently, people with diabetes are not receiving effective treatment for their increased risk of heart and circulatory disease. These findings identify new opportunities to prevent and treat complications from diabetes.”

Professor Sir Nilesh Samani, medical director of the British Heart Foundation, which funded the research, said:

“Although treatments for diabetes have improved, people with diabetes still have a higher risk of heart attacks. This research may partly explain why this is the case and potentially pave the way for new treatments to reduce the risk of heart attack for the millions of people living with Diabetes. ”