For roughly a decade, up to five times a month, Dave Thoen had diabetic seizures while in the middle of a conversation, in the car, and even while sleeping. He never knew when one might strike, and his family and friends had to help him in sometimes life-threatening situations. For type 1 diabetics like Thoen, the body mistakenly destroys insulin-producing islet cells in the pancreas and can’t properly regulate blood glucose. Like some diabetics, Thoen suffered from hypoglycemia unawareness, a complication in which he did not experience early signs of dangerously low blood sugar, such as sweating, dizziness, and extreme hunger—he’d just have a seizure or lose consciousness. Fortunately, Thoen was eligible to participate in the University of Minnesota’s human-to-human islet cell transplantation clinical trial at the Schulze Diabetes Institute (SDI). While islet transplantation remained experimental since the 1970s, recent clinical trial outcomes have made huge gains. Now, diabetes physicians and researchers—as well as patients like Thoen—view islet transplantation as a cure for diabetes.
Success in human islet transplantation
In 2008, the University was selected as one of three principal sites to conduct phase III clinical trials in human islet transplants—the final round of study before the U.S. Food and Drug Administration (FDA) determines whether it can be used as a standard therapy for diabetes. “It’s a very exciting area of study,” says Melena Bellin, M.D., a University pediatric endocrinology fellow and physician involved in the clinical trials. Bellin says new protocols using islets from two to four donors per transplant patient and changes to antirejection drugs have made an enormous difference in outcomes. Previously, about 10 percent of transplant recipients achieved insulin independence post-transplant, she explained. Today, nearly 90 percent of islet recipients become insulin independent posttransplant. “More than 50 percent maintain insulin independence at their five-year follow-ups,” Bellin adds. This year, three islet transplant recipients are celebrating seven years of insulin independence, with one patient reaching 10 years of insulin independence post-transplant.
Because the opportunity to make islet transplantation widely available holds such great potential, University researchers today are focused on solutions for possible roadblocks. There is a limited supply of human islet cells, which come from deceased donors. So, Bernhard Hering, M.D., SDI’s scientific director, is researching whether islet cells from medical-grade pigs could be used for human transplants. Last spring, his research team launched a pivotal pre-clinical trial to test pig islet cell transplants in monkeys. This study is the final hurdle before pig islet transplants can be tested in people. However, islet transplantation isn’t a panacea. Transplant patients swap their insulin regimen for a lifetime of immunosuppressive medication, which can cause sometimes serious side effects, to stop the immune system from rejecting transplanted islets. Researcher Meri Firpo, Ph.D., assistant professor in the University’s Stem Cell Institute and SDI, is working with a team of scientists to convert adult skin cells into stem cells, which can then generate islet cells. If successful, immunosuppressive drugs would no longer be required post-transplant.
‘Diabetes is history’
For Thoen, despite any potential side effects from islet cell transplants, deciding to undergo the procedure was easy. “At the end of the day, ‘Is it worth the side effects?’ wasn’t even a question for us. The number of times I could have killed myself or someone else [from unexpected seizures] made any side effects from immunosuppressive drugs a much better option.” In December 2008, Thoen received an islet transplant that rid him of hypoglycemia unawareness, dropping his need for insulin to just one-third of what he once required. “There’s nothing better than hearing that islets were successfully infused into a patient and to be able to call the donor family,” says Meg Rogers, director of procurement at LifeSource, the St. Paul-based organization from which SDI receives pancreases for islet transplants. “To share that news is an incredible experience.” Then in August 2009, Thoen underwent a second islet transplant and within a few weeks he was able to stop taking insulin altogether. “Diabetes is history,” he says, after having lived with diabetes for 22 years. “My family doesn’t worry about it. Hypoglycemia and insulin aren’t even in our vocabulary.” Further motivated by the success stories of patients like Thoen, SDI clinical trials are continuing—10 people have already received islet transplants since January 2010. While it’s too early to say when the study will go to the FDA, Bellin says that transplant patients in the trials are getting a much better quality of life. Thoen is among them. “We have quickly adapted to this new life [without diabetes], and it’s been a wonderful gift for us.”