Modification of the "Edmonton Protocol" to Allow for Successful Islet Transplantation From a Single Pancreas and Extension of the "Edmonton Protocol" to Kidney Transplant Recipients
Modification of the "Edmonton Protocol" to Allow for Successful Islet Transplantation From a Single Pancreas and Extension of the "Edmonton Protocol" to Kidney Transplant Recipients
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.
We anticipate that successful islet transplantation will establish a group of islet cell
 transplant patients who have normal blood sugars and do not need insulin injections. Some of
 this group will have received a kidney transplant as well. All these patients will be studied
 in great detail along with other investigators in our islet cell program to understand better
 the mechanisms of efficacy and side effects of islet transplant and these new
 immunosuppressive drugs.
Inclusion Criteria:

 Type 1 diabetes for > 5 years AND Hypoglycemia unawareness, not felt adequately by patient
 (glucose < 54mg/dL) in last 1.6 years, not otherwise explained, requiring outside help OR
 Metabolic lability/instability, characterized by hypoglycemia or ketoacidosis (>2 hospital
 < 12 mo), chaotic glucose profile (MAGE > 120mg/dL), disruption in lifestyle or danger to
 life, to self, to others OR Failure of intensive insulin management, as judged by an
 independent endocrinologist.