In 1997, the World Health Organization, the American Diabetes Association and other groups universally adopted new nomenclature for diabetes. Diabetes was no longer to be named by whether or not patients required insulin. The names Insulin-Dependent Diabetes and Childhood Onset Diabetes were changed to Type 1 diabetes. Type 1 diabetes was then further categorized by whether it resulted from an autoimmune attack (Type 1a) or a non-autoimmune attack (Type 1b). No changes have been made to the labels since that time.
With what we now know about Type 1 diabetes, it is time to define it by its pathophysiology. In other words, we need to label Type 1 diabetes in a way that incorporates all the underlying problems that cause this disease. Currently T1 is defined as a condition in which there is an autoimmune attack on insulin-producing cells, but many scientists no longer believe that this definition adequately portrays what we now know is happening.
It makes sense that we have, up until now, defined T1 by its autoimmune markers. We often can associate the onset of T1 as occurring after a recent virus, infection, or major illness, at which time the body’s immune system responds by making antibodies to attack the infection. Unfortunately, the immune system also sees the insulin-producing beta cells of the pancreas as foreign invaders and attacks them. Typically, with new onset T1, a blood test often shows an elevation of one of several types of antibodies, the most common being Glutamic Acid Decarboxylase-65 (GAD65) antibodies, which are a sensitive marker for autoimmune attack on the beta cells. So it’s clear that T1 has an autoimmune component, but what we have learned over the past three decades is that it is much more than that.
If it were just a matter of blocking an autoimmune reaction, we would have cured T1 by now, or at least have been able to offer better glucose control of it than is currently available. There have been more than 300 studies in mice and more than a dozen among new onset T1 patients using immune tolerance agents to try and block the immune system’s attack on insulin-producing beta cells. Despite great success in mice, it’s not enough for humans. An immune tolerance agent alone or a combination with more than one immune tolerance agent does not restore glucose levels to normal, nor does it protect the few remaining beta cells from further attack. For patients with new onset Type 1 diabetes, an immune tolerance agent like cyclosporine A may provide a 100% insulin-independent remission, but these numbers drop off to 50% after just a year. Over time, all patients required insulin again, and that’s the best-case scenario of immunotherapy. Many other immunosuppressant drugs fare more poorly.
Also, patients with T1 require the ability to generate new fully functional islets, which are composed of fewer beta cells and greater numbers of alpha, gamma, delta and epsilon cells. These cells make insulin, amylin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. All 6 hormones are required for perfect glucose regulation, which is why giving patients insulin alone doesn’t restore glucose metabolism to normal levels. From the research, it’s clear that T1 is both a disease of autoimmunity and a disease in which there is lack of beta cell generation.
I invite you to join my organization, Insulin Independence, on Twitter to help raise awareness and funding of the need to bring clinical trials that combine immune and regeneration therapies to the U.S.; these trials already are under way in Europe. The trials unite the immunotherapy and regeneration communities to study the results of using an immune tolerance agent with a regeneration agent, both of which are FDA-approved. It is our belief that when you help break specialized research scientists out of their silos, great things can happen.
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