Islet Cell Transplantation FAQs
Because islet transplantation is an experimental therapy, and the safety of the procedure is still being investigated, the eligibility criteria are strict to protect patients from undue risk. The eligibility criteria have been established in accordance with guidelines set by the Food and Drug Administration (FDA). The rationale for our major inclusion criteria are outlined below:
Type 1 Diabetes: Patients must have type 1 diabetes documented by very low c-peptide levels. Patients with type 2 diabetes are not currently eligible for islet transplantation therapy. Because type 2 diabetes results from a condition called “insulin resistance,” meaning the body does not respond to insulin normally, patients with this disease tend to have much higher insulin requirements. These patients would likely require more islets than can currently be provided in three islet transplant procedures (the maximum number of islet transplants a patient is allowed by the United Network of Organ Sharing). Islet transplantation is therefore not an optimal therapy for patients with type 2 diabetes.
Frequent low blood sugar episodes (hypoglycemia) or inability to sense low blood sugar (hypoglycemia unawareness): Patients being considered for a first islet transplant must be experiencing frequent low blood sugars or hypoglycemia unawareness placing them at risk of seizure, loss of consciousness, coma, or even death. The risk these patients face in their daily lives is thought to balance the risks associated with the islet transplant procedure and anti-rejection medications (see below). Also, because one of the major beneficial outcomes of islet transplantation is reduction/ elimination of low blood sugar episodes, these patients have the most benefit to gain from the procedure. For patients without a previous transplant or who are not facing the risks of frequent low blood sugar and hypoglycemia unawareness, the risks associated with the anti-rejection medications are not warranted.
Body Mass Index (BMI): Body mass index, or BMI, is a measure of body fat based on height and weight. The larger a person’s body mass, the more insulin they tend to require. Patients with high body mass indices are also at risk of insulin resistance or type 2 diabetes, further increasing their insulin requirements. Patients with large daily insulin requirements will likely require more islets to meet their metabolic demand than can currently be produced in three islet transplants. Further, following islet transplant, the insulin resistance is likely to exhaust the transplanted islets, so they will not function as well or for as long as in patients with smaller body masses and insulin requirements.
No evidence of significant kidney, heart, liver, or eye disease: The immunosuppressive drugs that are required to keep the islet transplant healthy can complicate these conditions.
No plans for future pregnancies: Women who are pregnant, nursing, or have plans for future pregnancies are not qualified to receive islet transplantation due to possibly dangerous side effects of the anti-rejection medications to the growing fetus/newborn.
In 2000 and 2001, investigators at the University of Alberta, Edmonton reported that more than 3 out of 4 diabetic patients treated with islet transplantation under their protocol were able to discontinue insulin injections for up to 20 months. This success reignited the world's enthusiasm about islet transplantation as a potential, long-awaited cure for type 1 diabetes and hundreds of new islet transplant research programs were created internationally, including one at the City of Hope.
A five-year follow-up report published by the Edmonton group in 2005 indicated that only about 1 out of 10 subjects remained off insulin 5 years after transplant. However, most patients who had to restart insulin needed only a fraction of their pre-transplant dose and continued to enjoy other important, long-lasting benefits of their transplants, including elimination of dangerous low blood sugar episodes and overall improvement in blood sugar control.
Outcomes from the first City of Hope clinical islet transplantation trial are similar to those initially reported by Edmonton and other leading islet transplantation programs. Some more recent islet transplant studies have used stronger (T-cell depleting) immunosuppression medications than the ones used in the Edmonton study, such as anti-thymoglobulin (ATG).
According to the Collaborative Islet Transplant Registry, 5-6 out of every 10 patients who received T-cell depleting immunosuppression for their islet transplant remained off insulin five years after transplant, which is consistent with the long-term outcomes of whole pancreas transplant.
Although one goal of our current T-cell depleting protocol is to achieve insulin-independence or the end of life-threatening hypoglycemic events with a single transplant, two to three islet transplant procedures may be needed to provide enough islet cells for a patient to discontinue insulin therapy.
While some patients may remain insulin-independent for several months or years after receiving islet transplant, others may need to restart insulin injections or insulin pump therapy at some point following the procedure(s). The majority of islet transplant recipients who have restarted insulin and have continued their anti-rejection medications have only needed to take a fraction of their pre-transplant dose.
Islet transplantation is an experimental procedure and may have side-effects related to the transplant itself and the anti-rejection medications.
Islet transplant-related side-effects may include bleeding at the site of islet infusion, infection, blood clot in the veins of the liver, and abdominal pain. The islet transplant may also cause the immune system to make antibodies to donor tissue. This may make it difficult to find a matching donor should a future organ transplantation become necessary.
Anti-rejection medications can have several side effects. Some of the most common include mouth ulcers, anemia (low red blood cells that cause symptoms of tiredness), nausea, vomiting, diarrhea, leg edema (swelling), high cholesterol or fat levels in the blood, liver problems, high blood pressure, fatigue, kidney problems, abnormal menstrual periods in women, and an increased risk of infection.
Anti-rejection medications may also increase the risk of developing cancer.
Patients participating in the T-cell depleting protocol may remain in the hospital up to a week after receiving the islet transplant to receive additional ATG doses and to watch for possible complications. Patients may also be required to stay longer under certain protocols to complete metabolic studies.
No. Islet transplantation involves transplanting mature insulin producing cells isolated from a human donor pancreas. Stem cells are cells that have not fully matured into a specific cell type. There is interesting basic science research currently being conducted to try to create insulin-producing cells from stem cells, but stem cell therapy for type 1 diabetes is not yet available for clinical treatment.
In type 1 diabetes, the beta cells (insulin-producing cells in the pancreas) are destroyed by the immune system. So, islet transplantation directly treats the disease by replacing the destroyed insulin-producing cells.
Because Type 2 diabetes is characterized by insulin resistance, patients with this disease tend to have much higher insulin requirements than patients with type 1 diabetes. As a result, type 2 diabetics would require more cells to achieve insulin independence than can currently be isolated for an islet transplant. In addition, insulin resistance is likely to exhaust the transplanted islets, so islet function and survival may be compromised in patients with type 2 diabetes. The procedure would therefore have few benefits for these patients.
The City of Hope is exploring new ways to improve the islet transplant procedure so that it may be offered in the future as an effective treatment for all patients with diabetes, including those with type 2 diabetes.
Participation in an islet transplantation clinical trial requires significant dedication and time commitment. Islet transplant recipients are required to take several medications multiple times per day for to keep their islet transplant healthy.
Patients are also followed carefully for at least two years after transplant to monitor for complications and to track how well the islet cells are working. Patients are required to report for very frequent clinic visits, which range from a few times per week immediately following the islet transplant to once per month.
Patients are required to keep very careful records of their medication intake, blood sugar levels and insulin doses throughout study follow-up.
A common misconception that many patients have is that after islet transplantation they will no longer need to test their blood sugar or take insulin. In fact, patients often require two to three separate islet transplants to get enough islets cells to discontinue insulin treatment, and some patients may never achieve insulin independence. After transplant, patients are asked to continue to test their blood sugar approximately seven times per day (before and after each meal and at bedtime). This helps the study physicians adjust insulin doses and monitor how well the islet cells are working after transplant. Often the first signs of islet graft dysfunction are rises in blood sugar, so continuing frequent self-blood glucose testing is an important way to track the health of the islets.