Islet cell transplantation in diabetes mellitus--from bench to bedside

Replacement of the patient's islets of Langerhans either by pancreas transplantation or by isolated islet transplantation is the only treatment of type I diabetes mellitus to achieve an insulin-independent, constant normoglycemic state. The expense for this benefit is the need for immunosuppressive treatment of the recipient with all its potential risks. Thus, indications for pancreas or islet transplantations at present exist almost exclusively in patients with end-stage renal disease who are waiting on dialysis for a kidney graft or in diabetics with an established kidney graft obliged to be immunosuppressed. Islet transplants possess significantly potential advantages over whole-gland transplants: it is a simple procedure with only small risk, if any; it offers the potential advantages of pre-transplant reduction of immunogenicity thus possibly obviating the need for continuous life-long recipient immunosuppression and it offers the future feasibility of transplanting heterologous (pig) islets. The effectiveness of this concept was demonstrated in animal experiments and may be successfully transferred into the clinical situation. In this case, the indications for islet transplantation may be extended to non-uremic type I diabetics including diabetic children. This group of patients is the ultimate target group for this most direct and appealing concept of treating type I diabetes. As of 1994, more than 200 adult islet allografts were reported to the International Islet Transplant Registry (ITR) at the Justus-Liebig-University, Giessen, Germany. A detailed analysis of 75 well-documented cases grafted between 1990 and 1993 revealed a one-year survival rate of the patients and islets of 95% and 28% (in terms of significant basal C-peptide secretion), respectively, and insulin independence was achieved in 11% of the cases after simultaneous islet-kidney (SIK) or islet-after-kidney (IAK) transplants. At present, there is no clinical data available and the follow-up studies of the posttransplant period are too short to draw any conclusions concerning the effects of islet transplants on diabetic secondary complications. Moreover, islet transplantation is still a clinical investigational procedure. Obviously, a number of fundamental steps will have to be taken before the appealing concept of transplanting adult pancreatic islets can attain clinical importance in the treatment of type I diabetic subjects. Islet cell transplantation has come the long way from animal experiments to successful clinical application, but, more research at the bench has to be performed before islet cell transplants will be successfully performed in non-uremic, non-kidney transplanted type I diabetic patients.