Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept.
Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept.
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DOI：
10.1097/tp.0b013e31818fe448
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发表时间：
2008-12-27
期刊：
影响因子：
6.2
通讯作者：
Alejandro R
中科院分区：
文献类型：
--
作者：
Faradji RN;Tharavanij T;Messinger S;Froud T;Pileggi A;Monroy K;Mineo D;Baidal DA;Cure P;Ponte G;Mendez AJ;Selvaggi G;Ricordi C;Alejandro R
Progressive graft dysfunction (GDF) and loss of insulin independence (II) has been invariably observed in islet transplant recipients under the ‘Edmonton protocol’. To reestablish II we performed supplemental islet infusions (SI) in recipients of allogeneic islet transplant alone, displaying GDF. To improve the engraftment and long-term graft function of SI, exenatide (EXN) and etanercept treatment at islet infusion, and long-term EXN treatment were tested in a non-randomized pilot clinical trial. Patients with GDF received SI under Edmonton-like immunosuppression with daclizumab induction, either without interventions (SI-control; n=5) or with EXN and etanercept treatment (SI-EXN; n=4). Clinical and metabolic profiles were assessed over 18–month follow-up. Long-term II (18 months) was observed in 100% of SI-EXN and in 20% of SI-Control (p=0.04). SI-EXN subjects demonstrated restoration of function better than that seen following initial islet infusions. Comparison of SI-EXN and SI-Control groups demonstrated better responses in SI-EXN subjects at three months post SI. Over the 18 months of follow-up, function was sustained in the SI-EXN subjects better than in SI-Controls. Acute effects of exenatide during MMTT and IVGTT results in improved first and second phase insulin release in response to intravenous glucose (IVGTT), and suppressed postprandial hyperglucagonemia after mixed meal tolerance test (MMTT). These results suggest that the combination of exenatide and etanercept improve engraftment and long term islet survival and function in subjects undergoing SI. This data however must be interpreted with some caution due to small sample size, lack of randomization and sequential comparison with historical controls.
