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Physicians Update


Physicians Update

Summer 2005: Transplantation

Pancreas Transplant Useful for Certain Diabetic Patients


For many years, pancreas transplantation has been o¤ered as an option for certain patients, and in the hands of experienced teams, it has proved e¤ective for those with long-time diabetes or diabetes with kidney failure, according to R. Mark Ghobrial, M.D., Ph.D., surgical director of the UCLA Pancreas Transplant Program.

The surgery involves transplanting a portion of the human pancreas as a way to stabilize blood sugar and glycohemoglobin levels without insulin; it is often indicated for diabetic patients with kidney failure, since they are already in line for a kidney transplant and can get both organs at once, Dr. Ghobrial explains. For patients with complications from diabetes—typically those experiencing the cumulative e¤ects from decades of type 1 disease—pancreas transplant without the kidney is also an option. “It’s usually three or more decades before type 1 diabetics develop renal failure, and not everyone does,” Dr. Ghobrial explains. Most patients with type 2 diabetes will not benefit from a pancreas transplant, because they are already able to make insulin; the problem is their lack of response to it, something that won’t change with the surgery.

Over the last year, the UCLA Pancreas Transplant Program team has achieved 100 percent patient and graft survival, a record Dr. Ghobrial attributes to the team’s surgical expertise as well as the links between the clinical work and the research component at UCLA. “If a patient has any type of problem, we are usually able to find insights through our research and clinical trials,” he says.

But despite successful outcomes, pancreas transplantation can’t come close to fulfilling the needs of all diabetic patients, Dr. Ghobrial notes. Besides the fact that there are so many insulin-dependent diabetics and so few organs, another problem is that, while patients who receive pancreas transplants may no longer require insulin, they need immunosuppressive medications. “Insulin is cheap, and immunosuppressive medications are very expensive,” Dr. Ghobrial notes. “For patients who develop renal failure, and need a kidney transplant, immunosuppression is going to be necessary anyway, so the pancreas transplant makes sense. But for those who do not have renal failure, we continue to treat with insulin.” That’s not ideal either, he adds—patients treated with insulin face quality-of-life concerns as well as being at greater risk for hypertension, high cholesterol and heart disease.

Islet Cell Transplantation 

Dr. Ghobrial and colleagues are hopeful that the long-term solution for these patients is islet cell transplantation. “Islet cell transplantation, while experimental at present, has great future promise,” explains Gerald Lipshutz, M.D., assistant professor in UCLA’s Liver and Pancreas Transplantation Program. UCLA and many other centers are hoping to overcomebarriers that have stood in the way of long-term survival of the islet cells. There was great hope in 2000 with the announcement of new successes in islet-cell transplants— removal of the islets containing the beta cells from a donor pancreas, followed by injection of these cells into a patient. But the optimism was dampened when the islets remained e¤ective for only a few years. “Once we identify the islet stem cell, then presumably it will be possible to massproduce islets for transplantation,” says Dr. Lipshutz. “But presently, when it takes two or three pancreases to have enough islets to make someone insulin-free—and then, perhaps only for a limited period of time—this therapy can only be thought of as an experimental endeavor, unlike solid-organ pancreas transplantation.”

UCLA has established the Larry L. Hillblom Islet Research Center, under the direction of Peter Butler, M.D., to focus on the problem. “The excitement right now is in stem cell di¤erentiation into islets, and islet regeneration,” says Dr. Lipshutz. “Ultimately, we would hope to be able to take a primordial stem cell—whether it be an adult-derived or embryonic cell—and have it develop into islet cells or beta cells of islets, to produce insulin. But the application of islet cell transplantation to patients outside of research protocols is, unfortunately, still years away.”

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