Alternative Theory for the Root Cause of Type 1 Diabetes

The root cause of type 1 diabetes (T1D) was believed to be the immune system incorrectly identifying insulin-secreting beta cells as a threat and destroying them. But new research results find that stressed beta cells are the real cause.

In a study published inNature Medicine, the investigators sought to better understand why the immune system attacks the pancreatic beta cells.

“Our findings show that type 1 diabetes results from a mistake of the beta cell, not a mistake of the immune system,” said lead investigator Bart Roep, PhD. “The immune system does what it is supposed to do, which is respond to distressed or ‘unhappy’ tissue, as it would in infection or cancer.”

The investigators used clues from cancer molecules successfully targeted by the immune system using immunotherapy. One of the cancer targets is a so-called nonsense protein, which is a result of the misreading of a DNA sequence that makes a nonfunctional protein.

This same type of protein error is also produced in beta cells in T1D, a disease that affects approximately 1.5 million Americans. This means that it’s the insulin gene itself that makes the mistake, making it a major target of the immune system.

According to investigators, the error product of the insulin gene is made when beta cells are stressed.

“Our study links anti-tumor immunity to islet autoimmunity, and may explain why some cancer patients develop type 1 diabetes after successful immunotherapy,” Roep said. “This is an incredible step forward in our commitment to cure this disease.”

The findings help further support the emerging concept that beta cells are destroyed in T1D by a mechanism that is comparable to classic antitumor responses, where the immune system is trained to survey dysfunctional cells, according to the authors.

“Our goal is to keep beta cells happy,” Roep said. “So we will work on new forms of therapy to correct the autoimmune response against islets and hopefully also prevent development of type 1 diabetes during anti-cancer therapy.”