Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept

Raquel N. Faradji, Thipaporn Tharavanij, Shari Messinger, Tatiana Froud, Antonello Pileggi, Kathy Monroy, Davide Mineo, David A. Baidal, Pablo Cure, Gaston Ponte, Armando J. Mendez, Gennaro Selvaggi, Camillo Ricordi, Rodolfo Alejandro

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

BACKGROUND.: Progressive graft dysfunction (GDF) and loss of insulin independence (II) have 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. METHODS.: 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 during 18-month follow-up. RESULTS.: 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 after initial islet infusions. Comparison of SI-EXN and SI-control groups demonstrated better responses in SI-EXN subjects at 3 months post-SI. During the 18 months of follow-up, function was sustained in the SI-EXN subjects better than in SI-controls. Acute effects of EXN during mixed meal tolerance test and intravenous glucose tolerance test results in improved first and second phase insulin release in response to intravenous glucose tolerance test and suppressed postprandial hyperglucagonemia after mixed meal tolerance test. CONCLUSION.: These results suggest that the combination of EXN and etanercept improve engraftment and long-term islet survival and function in subjects undergoing SI. This data, however, must be interpreted with some caution because of small sample size, lack of randomization, and sequential comparison with historical controls.

Original languageEnglish (US)
Pages (from-to)1658-1665
Number of pages8
JournalTransplantation
Volume86
Issue number12
DOIs
StatePublished - Dec 27 2008

Keywords

  • Diabetes
  • Etanercept
  • Exenatide
  • Glucagon
  • Graft dysfunction
  • Insulin
  • Insulin independence
  • Islet
  • Islet transplantation
  • Metabolism

ASJC Scopus subject areas

  • Transplantation

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