A PILOT STUDY OF ISLET TRANSPLANTATION IN NON-UREMIC DIABETIC PATIENTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The main goal of the study is to achieve long-term (greater than one year) insulin independence in patients with type I diabetes mellitus by means of islet cell transplantation from a single donor pancreas. The prevalence of type I diabetes in the United States is estimated to be 800,000 individuals, and the incidence is approximately 30,000 new cases each year. There are no thoroughly preventative or curative measures currently available. The closest has been the Diabetes Control and Complications Trial that demonstrated intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy (eye problems), neuropathy (nervous system problems), and nephropathy (kidney problems). The modality of beta-cell replacement by transplantation of the whole pancreas is the most successful method to control glycemia. Transplantationof the islets as free grafts extends the concept of beta-cell replacement therapy for patients with type I diabetes. The attraction of islet transplantation compared to conventional pancreas transplantation is its minimal morbidity and relative little use of hospital resources. Beta cell replacement therapy by means of islet cell transplantation, when successful, reverses hyperglycemia and the need for exogenous (from other sources) insulin therapy. The vast majority (95%) of islet transplants have been performed in patients who are either simultaneously receiving a kidney transplant or who have already received one and thus are committed to receiving systemic immunosuppressive therapy. Thus, all of these patients already suffered from advanced secondary complications of diabetes. The goal of islet transplantation is to be able to apply it early enough in the course of the disease so that these secondary vascular complications are prevented. For this to occur, anti-rejection regimens must be devised that minimize organ specific side effects while providing substantial protection from rejection. Following this lead, the University of Edmonton group have performed islet transplants in patients with type I diabetes and no evidence of chronic renal failure. Patients were excluded if their creatinine clearance was less than 60ml/minute/m2 or if the patient exhibited macroalbuminuria (greater than 300 mg excretion per 24 hours). Current Edmonton statistics (January 2003) state that one year after transplantation 84% of patients remain insulin free and that after three years, 89% of patients are still producing insulin. Within the window of the anti-interleukin-1 receptor antibody induction course, a second islet transplant was performed from a second donor and in each instance, the patient was able to discontinue insulin therapy. This study builds on the strengths of the previous experience and will limit accrual to eight patients that will be followed for at least one year post-transplantation. Patients will receive one or more islet cell transplants. Various tests will be performed to see if demand for exogenous insulin has been reduced or halted altogether.