β-cell Replacement Therapy
β-Cell replacement may be achieved through pancreas or islet transplantation in select candidates. Pancreas transplants are now accepted as a proven therapy, while islet transplants, though significantly improving, are still mostly done on an experimental basis.
Pancreas transplants are most often performed in combination with kidney transplantation, either as a simultaneous pancreas-kidney (SPK) transplant or as a pancreas-after-kidney (PAK) transplant. SPK and PAK transplants may be considered for individuals with late-stage kidney disease because the transplants can normalize glucose levels, which will prevent hypoglycemia and provide some protection for the transplanted kidney, and provide other benefits, including an improvement in quality of life. These recipients will already require immunosuppression for their renal transplants, which means the major additional risk is the operative procedure. SPK transplants function for an average of 9 years, compared with 6 years for PAK transplants.
There has been debate about pancreas transplant alone (PTA) in the absence of an indication for kidney transplantation because of the risks of mortality, morbidity, and immunosuppression. Outcomes have gradually improved, such that the procedure can be cautiously considered for individuals without renal failure who have unstable glucose control and hypoglycemia unawareness. Because of the risks of pancreas transplantation compared with traditional methods for controlling blood glucose levels, all available efforts to use exogenous insulin combined with technology, education, and glucose follow-up should be exhausted before PTA is performed. The durability of function averages 6 years, which is much better than islet transplantation but about the same as PAK and not as good as SPK.
A major appeal of islet transplantation is that it does not require major surgery. Moreover, outcomes have improved over the past decade such that normoglycemia without insulin is now maintained for an average of 3 years in specialized protocols. Even when insulin treatment is reinstituted, residual insulin secretion can help recipients maintain good control with less hypoglycemia and a less complicated regimen for several more years.
At the present time, few islet transplants are being performed and most are experimental. However, they can be considered as a treatment option for those who are poor candidates for whole-organ transplants. Importantly, their current success has established a proof of principle for cellular transplantation. Great progress is being made in finding an abundant source of healthy insulin-producing cells and in developing better ways to protect transplanted cells from immune destruction.[75,76] Potential solutions for the shortage of islets include embryonic stem cells, induced pluripotent stem cells, xenogeneic tissue, and various other potential sources—all the focus of ongoing research efforts. Another possible way to replenish the β-cell deficiency of diabetes is through regeneration of the endocrine pancreas; this too is being worked on intensively.
Consider solid organ pancreas transplantation simultaneously with kidney transplantation in patients with type 1 diabetes who have an indication for kidney transplantation and are poorly controlled with large glycemic excursions. (B)
Consider solid organ pancreas transplantation after kidney transplantation in adult patients with type 1 diabetes who have already received a kidney transplant. (C)
Judiciously consider solid organ pancreas transplantation alone in adults with type 1 diabetes, unstable glucose control, hypoglycemia unawareness, and an increased risk of diabetes-related mortality, who have attempted all of the more traditional approaches to glycemic control and have remained unsuccessful, yet are judged responsible enough to manage the antirejection medication regimen, risks, and follow-up required with an organ transplant. (C)
Consider referral to research centers for protocolized islet cell transplantation in patients with type 1 diabetes and debilitating complications of diabetes who are interested in research possibilities and fit the criteria for the research protocol. (E)
Diabetes Care. 2014;37(7):2034-2054. © 2014 American Diabetes Association, Inc.