There are two key questions diabetes researcher John Corbett, PhD thinks about a lot. The first is why. The second is how. As director of UAB’s new Comprehensive Diabetes Center, Corbett, a professor of biochemistry and molecular biology noted for his research on the mechanisms of pancreatic beta-cell destruction, is working to answer these important questions, and he is gathering a team of some of the most talented researchers in the field to help with the effort. “Why is it that siblings of a type 1 diabetic are at greater risk of developing the disease — suggesting a genetic component — yet when one twin gets type 1 diabetes, the other has only a 40 percent chance of having the disease?” Corbett asks. “Why — with obesity one of the strongest influences in developing type 2 diabetes — do so many overweight people never develop it? How do we use what we learn about diabetes to offer better treatments — and perhaps, one day, to even cure or prevent the disease?” Diabetes seems to occur when genetic susceptibility meets a precipitating event. The focus of Corbett’s current work is identifying the triggers that set the process into motion. “To date, we really can’t say with certainty what precipitates beta-cell death. Is it viral, bacterial or something chemical that activates the immune system?” asked Corbett. “We’re investigating the role of infections as one of the potential environmental factors that may initiate the development of type 1 diabetes.” Islet cell transplantation is another important area of research that offers the potential for actually curing diabetes. “Our team at UAB is following up on the Canadian study that uses a different combination of anti-rejection drugs to improve the survival rate of islet cells. These transplanted cells are producing insulin in patients and helping to reverse their diabetes. To make it work over the long term, we have to continue fighting rejection, and prevent whatever caused their diabetes from attacking the new cells.” The center also has research planned to fight the growing problem of type 2 diabetes. “The differences between type 1 and type 2 are blurring,” Corbett said. “There is now good evidence that inflammation may be a driving force in the development of insulin resistance and in the destruction of insulin producing cells. In fact, there is currently a clinical trial to evaluate potential of high dose aspirin to attenuate insulin resistance. We’re interested in mitochondrial DNA mutations, free radicals, and how the accumulation of mitochondrial DNA mutations at higher levels as one ages could cause the failure and death of insulin producing cells. We’ve been working with transgenic mice that accumulate mutations in insulin secreting beta cells, and we hope to soon be publishing preliminary data. At least, with type 2 diabetes is that there is a proven treatment — diet and exercise — easy to say, but difficult to do. But losing weight seems to help everything work better.” Putting Research into Practice As a medical research center, UAB is putting an emphasis on translational medicine — moving advances from the lab into patient care. A diabetes outpatient center at Kirkland Clinic brings together the latest treatment options for the many types of specialized care diabetics are likely to need. Vision, circulation and skin problems, neuropathy, kidney involvement and a wide range of other complications can be evaluated in one place and a treatment plan developed in consultation with the patient’s primary physician. There is also a program to transition juvenile diabetics who are growing up as they take more responsibility for their own care. At hospitals around town, the benefits of research are also being seen in more aggressive management of blood glucose in patients following heart procedures after studies showed better outcomes when fasting blood sugar levels are below 200. Now that insulin pumps are capable of sensing blood sugar, an artificial pancreas could be only a step away. Islet cell transplants are bringing the first glimmer of hope for a cure, and research into the causes of diabetes could even one day make the disease preventable. Perhaps, by the time children dealing with diabetes today grow up, they’ll know their child will never have to worry about checking blood sugar or practicing injections on oranges. An orange, at last, can be just a piece of fruit. November 2007