Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes

M. D. Bellin, R. Kandaswamy, J. Parkey, H. J. Zhang, B. Liu, S. H. Ihm, J. D. Ansite, J. Witson, P. Bansal-Pakala, A. N. Balamurugan, K. Papas, D. E.R. Sutherland, A. Moran, B. J. Hering

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154 Scopus citations

Abstract

We sought to determine the long-term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received one to two islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor-α blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 ± 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A1c levels and C-peptide production) and for adverse events associated with the study protocol. Of the six recipients, five were insulin-independent at 1 year, and four continue to be insulin-independent at a mean of 3.4 ± 0.4 years posttransplant. None of the six recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 ± 21.2 mL/min/1.73 m2 pretransplant to 82.6 ±19.1 mL/min/1.73 m2 at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of >3 years in four of six recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long-term graft survival.

Original languageEnglish (US)
Pages (from-to)2463-2470
Number of pages8
JournalAmerican Journal of Transplantation
Volume8
Issue number11
DOIs
StatePublished - Nov 2008

Keywords

  • Allograft survival
  • Everolimus
  • Islet graft
  • Islet transplantation
  • Islets
  • Thymoglobulin

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