New Theory About the Cause of Type 1 Diabetes

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The immune system mistakenly identifying insulin-secreting beta cells as a potential danger and, in turn, destroying them has long been considered the root cause of type 1 diabetes. Now, an international team of researchers led by City of Hope’s Bart Roep, Ph.D., the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes and professor/founding chair of the Department of Diabetes Immunology, has been able to justify a new theory about the cause of type 1 diabetes through experimental work. The study results were published online yesterday in the journal Nature Medicine.

Type 1 diabetes affects an estimated 1.5 million Americans and is the result of the loss of insulin-producing beta cells in the pancreas. 

Now Roep, along with researchers from the Leiden University Medical Center in the Netherlands, have found a mechanism in which stressed beta cells are actually causing the immune response that leads to type 1 diabetes.

“Our findings show that type 1 diabetes results from a mistake of the beta cell, not a mistake of the immune system,” said Roep, who is director of The Wanek Family Project for Type 1 Diabetes, which was recently created with gifts from the Wanek family and anonymous donors to support the institution’s goal of curing type 1 diabetes in six years. “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.”

In order to gain a better understanding of why the immune system attacks the body’s own source of insulin — the pancreatic beta cells in the islets of Langerhans — the team took some clues from cancer molecules that are targeted by the immune system after successful treatment of the cancer with immunotherapy.

One of these cancer targets is a so-called nonsense protein, resulting from a misreading of a DNA sequence that makes a nonfunctional protein. It turns out that the same type of protein error is also produced by the beta cells in type 1 diabetes. Therefore, Roep and the other researchers believe it is a ‘wrong read’ of the insulin gene itself that proves to be a major target of the immune system. This error product of the insulin gene is made when beta cells are stressed, Roep said.

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

According to the paper titled, “Autoimmunity against a defective ribosomal insulin gene product in type 1 diabetes,” the findings “further support the emerging concept that beta cells are destroyed in type 1 diabetes by a mechanism comparable to classical antitumor responses where the immune system has been trained to survey dysfunctional cells in which errors have accumulated.”

The results of the study give Roep new insight, he said, for his work in developing new vaccines to desensitize the immune system so that it will tolerate islets again, as well as for research into combining immunotherapy with more traditional diabetes treatments to reinvigorate islets.

“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.”

About City of Hope’s Program

Roep’s program at City of Hope plans to change the entire way we view a “cure,” shifting from a one-size-fits-all method of research and goals to a system of precision medicine; a way to offer individualized and personalized therapies for people with diabetes much in the same way cancer treatment does today.

The program will draw heavily from a biorepository, something Dr. Roep says will save millions of dollars and many years in helping them embrace the concept of diabetes being unique in almost every individual. Armed with that knowledge they will dig back into human clinical studies that may not have succeeded on a mass scale and look to see if they can help patients on a smaller scale.

For instance, if a study failed for 70 percent of the participants, it may have held answers for other 30 percent.

The focus at City of Hope will be threefold: to stop the progression of the disease (something Roep calls the “low hanging fruit” of the effort), get people off injections for good (something he admits is “much more of a challenge but not impossible,”), and preventing, stopping, and reversing complications.

The work described in the Nature Medicine paper was supported by the Dutch Diabetes Research Foundation, the DON Foundation and JDRF.

Source: City of Hope press release.

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9 Comments on "New Theory About the Cause of Type 1 Diabetes"

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Gail Morrison

Very interesting research. Our oldest was diagnosed 3 years ago. He had a ruptured appendectomy 3 months prior to the diagnosis – all pre-op lab test were normal prior to surgery. I believe the beta cells reacted to the sepsis causing an autoimmune response. This is the closest I have found to a “cure”. Thank you all for your research time and effort.

diane

My granddaughter was diagnosed at age 8. At the time everyone remarked on how lucky we were that a cure was right around the corner. That was one long corner, it will soon be 11 years. It is hard to believe with all the world’s greatest scientists that we seem to still be so far from a cure

diane

Diane

Roni
I’m so happy to finally hear about researchers that are still done to find the cause rather than a cure based only on the information we have, accepting it as facts. I believe some of what is said in the article is true, but only part of it. Our immune system is not to blame! But I also believe that our genes and beta cells are not THE problem. Recently I’ve been reading a book that suggest a totally different approach to the cause, as well as treatment of diabetes. According to this book the cause is fungi that enters… Read more »
Karen martinez

Been a diabetic since I was 29 . I am 62 now almost a human pin cushion . Hope they come up with a cure soon before it’s too late for me !

rick phillips

The part I do not understand is if it is the beta cell, then why does Beta cell transplant fail? Yes, beta cells die and are regenerated each few months, but if it is the beta cell then why te issue with trying to keep beta cells alive for even short periods? I find it difficult to understand.

Brian

What about the “jacket protein covering” that the beta cells take on when stressed? Perhaps they are not bad beta cells but rather have bad coverings that the immune system attacks.

Arun Mehta

Diabetes is dreaded disease need urgent attention, it spoils life. I am diabetic since 33 years and on insulin since 15 years . I hope something will be done in near future.

Melissa fair

I’ve been Type 1 Diabetic over 20 years. 17 when I got diagnosed. It definitely challenges life but at least we can take medicine to help control it. Insulin is only a part of the daily routines to control that sugar. Remember, it could me worse, I’m surprised as well that there’s not been a cure yet.

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