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Supplemental Islet Infusions Restore Insulin Independence After Graft Dysfunction in Islet Transplant Recipients

Koh, Angela; Imes, Sharleen; Kin, Tatsuya; Dinyari, Parastoo; Malcolm, Andrew; Toso, Christian; Shapiro, A M. James; Senior, Peter

doi: 10.1097/TP.0b013e3181bcdbe8
Clinical and Translational Research

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.

Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada.

The Clinical Islet Transplant Program receives funds from a Juvenile Diabetes Research Foundation Islet Transplant Center Grant, from the National institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (DK59101) and from the Immune Tolerance Network. The Program is further supported by Capital Health and Alberta Health and Wellness (Province Wide Services). Generous philanthropic support is provided by the Roberts Family, the North American Foundation for the Cure of Diabetes, the Alberta Building Trades and from the Diabetes Research Institute Foundation Canada (DRIFCan).

Koh, Imes, and Senior participated in performance of research, data analysis, and writing of paper; Kin, Dinyari, Malcolm, Toso, and Shapiro participated in the performance of research and assisted in writing of this article.

The authors have no conflict of interest to declare.

Address correspondence to: Peter Senior, M.B.B.S., Ph.D., Clinical Islet Transplant Program, 2000 College Plaza, 8215-112 Street, Edmonton AB Canada T6G 2C8.

E-mail: petersenior@ualberta.ca

Received 19 June 2009. Revision requested 6 July 2009.

Accepted 17 August 2009.

© 2010 Lippincott Williams & Wilkins, Inc.