There is currently strong evidence to support the concept that the secondary complications of diabetes will be prevented, or their progression arrested, if constant homeostatic control of carbohydrate metabolism can be achieved. it is also evident that exogenous insulin cannot provide the necessary control. In contrast, both segmental pancreatic transplantation and islet transplantation can achieve control of blood glucose levels. Many of the technical problems that beset early attempts at whole gland or segmental pancreatic transplantation have now been overcome. Elimination of the duodenal cuff has prevented necrosis, bleeding, and fistula due to rejection at the duodenojejunal anastomosis. Improved vascular techniques have lessened the incidence of thrombosis at vascular anastomoses. Problems related to the handling of pancreatic exocrine secretions still exist, but initial results with free intraperitoneal drainage are encouraging. However, segmental pancreatic grafts will always be restricted to one recipient per donor. In contrast, islet cell transplantation is technically less hazardous, the morbidity and mortality rates are lower, and, ultimately, the possibility exists of transplanting several diabetic recipients with islet tissue procured from one donor. Improved techniques to increase the yield of islet tissue from a single pancreas are required. The outstanding problems for both types of transplantation remain those of allograft rejection and the immunosuppression necessary to prevent it. To date, specific and nonspecific immunosuppressive protocols that are highly effective in renal allograft models are considerably less effective for pancreatic allografts. Furthermore, experiments in rats have demonstrated that islet tissue is extremely immunogenic and exquisitely sensitive to allograft rejection mechanisms. High doses of steroids presently in use in immunosuppressive regimens may produce a diabetogenic effect sufficient to mask any graft function occurring before rejection. The major risk of pancreatic transplantation is related to the immunosuppression. Therefore, only diabetic patients who are prone to the morbid, life-threatening complications of their disease and who already require maintenance immunosuppression following a renal allograft are presently considered candidates for pancreatic transplantation. Until more specific and safer immunosuppresive drugs are available, it will be some time before the indications for pancreatic transplantation can be broadened to include patients who have not already developed the secondary complications of diabetes mellitus. In contrast, pancreatic islet cell autotransplantation may soon become established in prevention of insulin-independent diabetes in patients undergoing 95% pancreatectomy for relief of pain in chronic pancreatitis.
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