Journal
TRANSPLANTATION
Volume 89, Issue 3, Pages 361-365Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181bcdbe8
Keywords
Islet transplantation; Graft dysfunction; Type I diabetes
Categories
Funding
- Juvenile Diabetes Research Foundation Islet Transplant Center
- National institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [DK59101]
- Immune Tolerance Network
- Capital Health and Alberta Health and Wellness (Province Wide Services)
- Roberts Family
- North American Foundation for the Cure of Diabetes
- Alberta Building Trades
- Diabetes Research Institute Foundation Canada (DRIFCan)
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Background. The ability of supplemental islet infusions (SII) to restore insulin independence in islet transplant recipients with graft dysfunction has been attributed to the coadministration of exenatide. However, improving islet transplant outcomes could explain the success of SII. We aimed to determine the effect on islet graft function and insulin independence of SII using these new protocols, without the use of exenatide. Methods. Seventeen islet transplant recipients underwent SIIs after developing graft dysfunction requiring insulin use. For induction therapy, four subjects received daclizumab induction therapy, whereas 13 subjects received thymoglobulin and etanercept. Maintenance immunosuppression consisted of sirolimus+tacrolimus or tacrolimus+cellcept. Results. SII was performed 49.3 +/- 4.8 months (mean +/- SEM) after the preceding islet transplant. Subjects received significantly lower islet mass with their SII compared with initial transplant(s) (6076 +/- 492 vs. 9071 +/- 796 IEQ/kg; P=0.003). Fifteen of the 17 subjects (88.2%) became insulin independent 2.4 +/- 0.5 months after SII. Insulin-independent duration after SII exceeded that of the initial transplant(s) (24.8 +/- 2.2 vs. 14.2 +/- 2.6 months by Kaplan-Meier analysis, P=0.009). Subjects show improved glycemic control after SII (HbA1c 7.0% +/- 0.2% pre-SII vs. 6.1% 0.2% post-SII, P=0.005) and did not become immunosensitized. Conclusion. Using current protocols, SII in the absence of exenatide results in impressive insulin-independence rates and the durability of insulin independence seems to be promising. However, a beneficial effect of exenatide should not be discounted until tested in randomized controlled studies.
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