The experience of the Edmonton Group with islet transplantation and use of the "Edmonton Protocol" provides much promise for T1DM patients. However, the need to use 2 or more donor pancreases to achieve freedom from insulin shots limits the widespread use of this protocol. Two classes of oral antidiabetic drugs improve insulin action and reduce the amount of insulin needed to have normal blood sugars. The first part of the proposed project (Group 1) will use these drugs in conjunction with the Edmonton Protocol to allow for successful islet transplantation from islets isolated from a single pancreas.

The Edmonton Protocol is a treatment, not a cure. It requires the long-term use of powerful immunosuppressive drugs that are expensive and increase the risk of infection and cancer. T1DM patients who have a functioning kidney transplant already have to use immunosuppressive drugs, and they are still at risk of recurrent diabetic kidney disease and other complications of diabetes. Islet transplantation in these patients has only rarely been successful in the past in part because the usual immunosuppressive drugs used in kidney transplantation cause diabetes and actually harm the transplant kidney in other ways. The immunosuppressive drugs used in the Edmonton Protocol are less likely to cause diabetes and are also less harmful to the kidney. In the second part of this project (Group 2), we will transplant islets into kidney transplant patients after they have switched to the immunosuppressive medications used in the Edmonton Protocol. Even if some of the patients do not get islet transplants or still need insulin shots after islet transplantation, we expect to see improvement in kidney function and blood glucose control.