Summer 2006

Transplant Options for Type 1 Diabetes

Insulin dependent (type I) diabetes frequently leads to severe health complications in patients whose blood sugar levels cannot be adequately controlled. UCSF performs two procedures designed to provide selected patients with a healthy supply of insulin-producing beta cells — solid organ pancreas transplantation and pancreatic islet transplantation. With technological advances and better immunosuppressive regimens, the success of both procedures has greatly improved in the last five years, according to Peter Stock, M.D., Ph.D., who with Andrew Posselt, M.D., Ph.D., heads the UCSF Pancreas and Pancreatic Islet Transplant Program.

Pancreas or islet transplants are typically performed in patients who have difficulty in controlling their blood sugar levels or who have developed other complications of the disease, such as kidney failure. In fact, the majority of patients who are candidates for pancreas transplantation have kidney failure from their diabetes and receive a kidney as well as a pancreas.

Pancreatic Islet Transplantation

Particular strides have been made in the last five years in improving outcomes for pancreatic islet transplantation. Islets, which contain the insulin-secreting beta cells, are retrieved through extensive processing of a cadaver donor pancreas and are then injected into the patient without the need for major surgery.

Islet transplantation was first performed in a diabetic patient in 1974, but over the next 25 years very few patients were able to achieve insulin independence with the procedure. In 2000, a group from the University of Alberta developed a strategy — the Edmonton protocol — that greatly improved the success of islet transplants. The protocol uses multiple infusions of islets from different donors to achieve insulin independence and eliminates steroids, known to be toxic to beta cells, from the immunosuppression regimen.

At UCSF the labor-intensive islet processing procedure is carried out at the Islet and Cellular Transplantation Facility. When the processing procedure is completed, the recipient is admitted to the hospital and the pancreatic islets are infused into the portal vein. The islets then migrate to the liver where they begin producing insulin.

Because islet transplantation is minimally invasive, it can be offered to patients with severe cardiovascular disease who cannot tolerate open surgery, Posselt said. However, islet transplants generally do not last as long as solid organ pancreas transplants. The beta cells appear to stop working after a period of time, requiring an additional infusion from another donor.

Nonetheless, there are patients who remain insulin independent five years following the islet infusion. Why the cells stop functioning in some cases is not clear, said Posselt. It may be that the underlying autoimmune response that produces diabetes damages the islets. Researchers also speculate that regenerative cells within the pancreas that would normally replenish beta cells are not present in the islet infusions. The presence of these regenerative cells may account for the fact that long-term graft survival and insulin independence rates are higher with solid organ transplants. Islet cell replacement may also not be effective in patients with a large body mass index and large insulin requirements.

Donor profiles are more forgiving for islet transplants compared to solid organ transplants. Donors can have some comorbid conditions and be up to 55 years old. The ideal donor is overweight, Posselt said, since the islets tend to be larger than in normal weight individuals and the yield of beta cells is consequently higher.

Combined Pancreas and Kidney Transplants

Kidney disease develops in about 40 percent of patients with type I diabetes, and many eventually require a kidney transplant. Since 1989, UCSF has performed combined pancreas/kidney transplants in more than 350 diabetic patients. The double transplant corrects patients' renal failure and greatly improves their blood sugar control without the need for insulin. In addition, it may slow the development of other diabetic complications such as diabetic retinopathy, neuropathy and vascular disease.

Prior to the mid-1990s, the rate of organ rejection in pancreatic transplantation was frustratingly high. Success rates have improved dramatically thanks to better immunosuppressive drugs. Rejection rates have dropped from 80 percent to less than 20 percent in the last five to 10 years. A pancreas transplant usually delivers on its promise of erasing the underlying diabetes. About 90 percent of patients who receive a new pancreas no longer need to take insulin after surgery. Many of these patients remain insulin independent five to 10 years after the transplant.

A pancreas transplant poses significant surgical risks, so patients must be physically able to undergo the procedure. The supply of donor organs is limited. For a solid organ transplant, the pancreas must be in near perfect condition, Stock said. Most cells within the pancreas produce digestive enzymes. Any leakage from damage to the organ poses a risk to the recipient. To ensure that the pancreas is in optimal condition, deceased donors are generally 45 years of age or younger, with no underlying disease.

Consultations and Referrals

For more information about solid organ pancreas or islet transplantation, please call (415) 353-1551.

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