Benefits and Risks of Solitary Islet Transplantation for Type 1 Diabetes Using Steroid-Sparing Immunosuppression

Abstract

OBJECTIVE -The aim of this study was to describe the National Institutes of Health's experience initiating an islet isolation and transplantation center, including descriptions of our first six recipients, and lessons learned.RESEARCH DESIGN AND METHODS -Six females with chronic type 1 diabetes, hypoglycemia unawareness, and no endogenous insulin secretion (undetectable serum Cpeptide) were transplanted with allogenic islets procured from brain dead donors. To prevent islet rejection, patients received daclizumab, sirolimus, and tacrolimus.RESULTS -All patients noted less frequent and less severe hypoglycemia, and one-half were insulin independent at 1 year. Serum C-peptide persists in all but one patient (follow-up 17-22 months), indicating continued islet function. Two major procedure-related complications occurred: partial portal vein thrombosis and intra-abdominal hemorrhage. While we observed no cytomegalovirus infection or malignancy, recipients frequently developed transient mouth ulcers, diarrhea, edema, hypercholesterolemia, weight loss, myelosuppression, and other symptoms. Three patients discontinued immunosuppressive therapy: two because of intolerable toxicity (deteriorating kidney function and sirolimus-induced pneumonitis) while having evidence for continued islet function (one was insulin independent) and one because of gradually disappearing islet function.CONCLUSIONS -We established an islet isolation and transplantation program and achieved a 50% insulin-independence rate after at most two islet infusions. Our experience demonstrates that centers not previously engaged in islet transplantation can initiate a program, and our data and literature analysis support not only the promise of islet transplantation but also its remaining hurdles, which include the limited islet supply, procedure-associated complications, imperfect immunosuppressive regimens, suboptimal glycemia control, and loss of function over time. Diabetes Care 26:3288 -3295, 2003A lthough it is well established that individuals with immune-mediated type 1 diabetes can minimize their risk for long-term complications by maintaining near-normal blood glucose (1,2), it is equally well established that maintaining normal blood glucose concentrations is often quite difficult (3), with one price of such efforts being a threefold greater risk for serious hypoglycemia (4). Currently, pancreas transplantation can restore insulin independence in up to 90% of patients 1 year after surgery, but the procedure is technically demanding and is associated with serious complications and high mortality. In fact, our recent analysis suggests that solitary pancreas transplantation may decrease overall survival for those patients with normal kidney function (4a). Because many of the postsurgical complications are attributable to the non-insulinproducing pancreatic exocrine tissue (5), investigators have asked whether transplanting just the insulin-producing islets might be similarly effective but safer (6,7). Thus, since early reports of islet transplan...

Quality of Life After Islet Transplantation

“…In summary, our data showed that islet transplantation results in improvement of selected aspects of QOL, and that there is little, if any, negative impact of the procedure, an important observation in view of the question as to whether chronic immunosuppression side effects might outweigh the benefits of improved metabolic control (21). We also show that re-introduction of insulin therapy is a fundamental independent variable that affects QOL outcomes, and we suggest that larger patient samples and longer follow-ups will strengthen our conclusions.…”

Assessment of Human Pancreatic Islet Architecture and Composition by Laser Scanning Confocal Microscopy

“…Human islets were prepared by the Cell Processing Unit, Department of Transfusion Medicine, National Institutes of Health (Hirshberg et al 2003a) Non-human primate islets from rhesus macaques were prepared by the Islet and Autoimmunity Branch of the NIH (Hirshberg et al 2002a,b). After isolation, human and nonhuman primate islets were shipped in CMRL media by overnight courier to Vanderbilt University and cultured for an additional 24 hr in CMRL media, 95% CO 2 /5% O 2 at 37C.…”

Prevention of Bleeding After Islet Transplantation: Lessons Learned from a Multivariate Analysis of 132 Cases at a Single Institution

“…Life-threatening acute bleeds have been reported in islet recipients following the percutaneous approach (14)(15)(16) and this serious complication is potentially avoidable by obliteration of the intrahepatic portal catheter track.…”