Improvement in β-Cell Secretory Capacity Following Human Islet Transplantation According to the CIT07 Protocol

  1. Ali Naji2
  1. 1Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, the
  2. 2Department of Surgery, Division of Transplantation, the
  3. 3Department of Radiology, Division of Interventional Radiology, and the
  4. 4Department of Pathology & Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
  1. Corresponding author: Michael R. Rickels, E-mail: rickels{at}mail.med.upenn.edu

Abstract

The Clinical Islet Transplantation 07 (CIT07) protocol utilizes anti-thymocyte globulin and etanercept induction, islet culture, heparinization and intensive insulin therapy, with the same low-dose tacrolimus and sirolimus maintenance immunosuppression as in the Edmonton protocol. To determine whether CIT07 improves engrafted islet β-cell mass, our center measured β-cell secretory capacity from glucose-potentiated arginine tests at days 75 and 365 post-transplant, and compared the results to those previously achieved by our group with the Edmonton protocol, and to normal. All subjects were insulin-free with CIT07 subjects receiving fewer islet equivalents from a median 1 vs. 2 donors in Edmonton subjects. The acute insulin response to glucose-potentiated arginine (AIRpot) was greater in CIT07 than Edmonton and less in both cohorts than normal, with similar findings for C-peptide. The CIT07 subjects who completed reassessment at day 365 exhibited increasing AIRpot by trend relative to day 75. These data indicate that engrafted islet β-cell mass is markedly improved with the CIT07 protocol, especially given more frequent use of single islet donors. While several peri-transplant differences may have each contributed to this improvement, the lack of deterioration in β-cell secretory capacity over time in CIT07 suggests that low-dose tacrolimus and sirolimus are not toxic to islets.

  • Received December 20, 2012.
  • Accepted April 24, 2013.

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