Pancreas and islet transplantation for patients with diabetes.

Abstract

Hi s t o r i c a l l y, patients with diabetes have expended tremendous eff o rt in pursuing a re t u rn to norm o g l y c e m i a . The relatively recent results of the Diabetes C o n t rol and Complications Trial (DCCT), demonstrating an approximate 50% re d u ction in eye, nerve, and kidney complications in a group of patients re c e i v i n g intensive treatment for hyperglycemia (1), have made this pursuit even more intense. Successful pancreas and islet transplantations are currently the only therapies that re p roducibly achieve normoglycemia by reestablishing endogenous insulin secretion responsive to normal feedback re g u l ation. This re p o rt briefly considers the h i s t o ry, techniques, clinical results, and risk-benefit relationship of successful panc reas and pancreatic islet transplantations in hyperglycemic patients with long-standing diabetes. PANCREAS T R A N S P L A N TAT I O N — P a n c re a t i c transplantation was first used for the tre a tment of type 1 diabetes in humans in 1966 (2). In that early era, the rates of graft and patient survival were low, so very few proc e d u res were perf o rmed until 1978. Important steps toward improving surgical re s u l t s included the introduction of impro v e d i m m u n o s u p p ressive regimens, especially the use of cyclosporine and anti‐T- c e l l agents, new surgical techniques, and the selection of healthier recipients. In the past decade, the number of pro c e d u res perf o rmed has steadily increased each year (3). By the end of 1997, nearly 10,000 panc reatic transplantations had been re c o rd e d in the International Pancreas Tr a n s p l a n t R e g i s t ry, and in that year alone, more than 1,200 pro c e d u res were re p o rted. The results from diff e rent centers vary depending on operative experience and patient selection. The 1994‐1997 data from the I n t e rnational Pancreas Transplant Registry (3) indicate an overall 1-year patient survival rate of 90% (Fig. 1). The 1-year rate of graft survival (defined as total fre e d o m f rom insulin therapy, normal fasting blood glucose concentrations, and normal or only slightly elevated HbA 1 c values) was 82% when a pancreas and a kidney were transplanted simultaneously (SPK), 71% when a p a n c reas was transplanted after kidney transplantation (PAK), and 62% when a p a n c reas was transplanted alone (PTA ) . Most pancreatic transplantations in diabetic patients with renal failure are perf o rmed at the same time as or after kidney transplantation. The objectives in this instance are to render the patient free of exogenous insulin therapy, to arrest the p ro g ress of ongoing secondary complications, to protect the transplanted kidney f rom hyperglycemia, and to improve quality of life. In unusual circumstances, the p a n c reas is transplanted alone, but the decision to do so is more difficult. In these patients, kidney transplantation and i m m u n o s u p p ression are not already indicated, and survival of pancreas grafts when transplanted alone is lower than when transplanted simultaneously with a kidn e y. Inclusion criteria for PTA include that the patient is severely metabolically unstable, has severe autonomic dysfunction, or generally has a very poor quality of life because of the effects of chronic diabetes. Although the success rate of PTA is lower, this may be due to the lack of a marker for p a n c reas rejection that is as sensitive as s e rum creatinine is as a marker for kidney transplant rejection. Hence, rejection is m o re difficult to detect and anti-re j e c t i o n t reatment is initiated later. Technique