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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
Shapiro, A M James
Senior, Peter
Published in Transplantation. 2010, vol. 89, no. 3, p. 361-365
Abstract 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.
Keywords Antilymphocyte Serum/therapeutic useBlood Glucose/metabolismC-Peptide/bloodDrug Therapy, CombinationFemaleHemoglobin A, Glycosylated/metabolismHumansHyperglycemia/drug therapy/epidemiologyHypoglycemic Agents/ therapeutic useImmunoglobulin G/therapeutic useImmunosuppressive Agents/therapeutic useInsulin/ therapeutic useIslets of Langerhans Transplantation/immunology/ methodsMalePostoperative Complications/blood/drug therapyReceptors, Tumor Necrosis Factor/therapeutic useSirolimus/therapeutic useTacrolimus/therapeutic use
PMID: 20145529
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Research group Transplantation et hépatologie (905)
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KOH, Angela et al. Supplemental islet infusions restore insulin independence after graft dysfunction in islet transplant recipients. In: Transplantation, 2010, vol. 89, n° 3, p. 361-365. doi: 10.1097/TP.0b013e3181bcdbe8 https://archive-ouverte.unige.ch/unige:20693

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Deposited on : 2012-05-23

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