Rationale Of Islet Transplantation For Patients With Type 1 Diabetes

Pancreas transplantation is a near perfect means of normalizing glycosylated hemoglobin levels — the most important determinant of stabilizing or reversing microvascular complications.5 Successful pancreas transplantation will result in a durable normoglycemic and insulin-independent state6 that can reverse the diabetic changes in the native kidneys of patients with early diabetic nephropathy;7 reverse peripheral sensory neuropathy;8 stabilize advanced diabetic retinopathy;9 and significantly improve the quality and duration of life.10,11

However, there are important considerations with pancreas transplantation that currently preclude it as therapy for all patients with type 1 diabetes. It is unrealistic that all patients with diabetes could be transplanted to allow for early intervention in the disease process. There are too few organs (only about 1400 cases are performed annually in the U.S.). Pancreas transplantation involves significant surgery that

Organ Transplantation, 2nd edition, edited by Frank P. Stuart, Michael M. Abecassis and Dixon B. Kaufman. ©2003 Landes Bioscience.

precludes consideration in patients with significant co-morbid medical conditions (i.e., cardio- and peripheral vascular disease). Lifelong immunosuppression is required to prevent graft rejection. Transplanting the whole pancreas is not necessary to achieve an insulin independent state since it is only the islets that are required for glucose homeostasis. In fact, excluding the exocrine pancreas may avoid some of the complications of pancreas transplantation.

In the early 1970s transplantation of isolated pancreatic islets for treatment of type 1 diabetes in humans was seriously considered when the technique was proven feasible in small animal models.12-15 The demonstration that islet transplantation ameliorates the basic metabolic defects of the hyperglycemic state and stabilizes or reverses early secondary lesions provides a strong impetus and rationale for pursuit of such an approach in humans. Importantly, many of the factors that limit application of whole pancreas transplantation for treating diabetes are more likely to be overcome if isolated islets are used as the source of endocrine tissue. Therefore, islet transplantation is a treatment option that has generated great enthusiasm and is being developed for a potentially broader scope of patients.

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