More than 100,000 people in the Netherlands live with type 1 diabetes (T1D). This disease develops when the body’s own immune cells destroy the insulin-producing cells (beta cells) in the pancreas. As a result, people with T1D produce little or no insulin. Insulin is a hormone that enables the body to absorb sugar from the blood, providing muscles and organs with energy. It keeps blood sugar levels balanced — too much (hyperglycemia) or too little (hypoglycemia) can seriously harm health.

At present, there is no cure for T1D. Patients must administer insulin for life using an insulin pen or pump. Despite this treatment, people with T1D remain at increased risk of complications such as eye disease, kidney damage, and cardiovascular problems — meaning that insulin therapy is not a cure.

Stress as a culprit

Why some people develop T1D while others do not remains unclear. For a long time, scientists believed that T1D was caused by a mistake in the immune system that led it to attack the body’s own beta cells. In recent years, this view has shifted — partly due to research from Roep and his team. Their work shows that it is not the immune system itself that malfunctions, but rather the stressed beta cells that send out distress signals, making the immune system see them as “faulty.”

Roep explains: “Beta cells are extremely hard workers. Each beta cell can produce up to a million insulin molecules per minute. This ensures that sugar is quickly absorbed from the blood after a meal. But this process also causes a great deal of stress for the beta cells. When a beta cell can no longer cope with that stress, it unintentionally sends a signal to the immune system to destroy it. We have now discovered why some people’s beta cells can handle this stress better than others.”

A valve to release the pressure

“One small variation in the DNA of the insulin gene provides protection against T1D,” says Dr. René van Tienhoven, researcher and T1D patient himself. About 40% of all Dutch people carry this protective variant. Van Tienhoven explains: “The beta cells of people with the protective variant are equipped with a kind of valve. This valve allows them to release pressure under high stress, keeping them hidden from the immune system. Thanks to this valve, the beta cells stay fitter and function better. They’re essentially super beta cells.”

A better prognosis

One in five people with T1D has the protective genetic variant — meaning their beta cells have the valve — yet they still develop diabetes. This shows that the valve does not offer complete protection. However, these patients tend to experience a milder course of the disease. “As long as they inject enough insulin, these T1D patients often retain some of their own beta cells. That means they still produce a little insulin themselves and can regulate their blood sugar more effectively. Their prognosis is therefore better: this group rarely develops complications anymore,” says Van Tienhoven.

Personalized treatment

Thanks to LUMC researchers, we now know that the disease process in T1D can differ from person to person — partly due to changes in the DNA of the insulin gene. Insulin therapy addresses the symptoms, not the cause of T1D. Various experimental therapies are being tested in the quest for a cure, but so far these have worked only in a subset of patients. Researchers are now investigating whether the genetic variant can explain why certain interventions work for some individuals but not for others. This knowledge will help tailor treatments more precisely to each patient.

Roep explains: “Testing patients for the genetic variant provides important information about the severity and prognosis of the disease, as well as opportunities for more personalized treatment.”

The discovery also opens the door to promising future applications for T1D patients. The LUMC currently performs islet transplants, a complex procedure in which clusters of pancreatic cells — known as the islets of Langerhans — are isolated from a donor pancreas. This procedure is performed exclusively at LUMC in the Netherlands. In addition, LUMC scientists are growing stem cells into beta cells. Roep notes: “We can test pancreas or stem cell donors for the protective variant to improve the outcomes of islet transplantation and stem cell therapy. In the future, we could even introduce the valve into lab-grown beta cells through a small genetic adjustment. Although these methods are not yet ready for clinical use, they offer great promise for the future.”

More information

The research findings have been published in Cell.