The impact of islet mass, number of transplants, and time between transplants on graft function in a national islet transplant program

Shareen Forbes*, Anneliese J. Flatt, Denise Bennett, Robert Crookston, Mirka Pimkova, Linda Birtles, Andrew Pernet, Ruth C. Wood, Keith Burling, Peter Barker, Claire Counter, Alistair Lumb, Pratik Choudhary, Martin K. Rutter, Miranda Rosenthal, Andrew Sutherland, John Casey, Paul Johnson, James A.M. Shaw

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p =.002) two transplant recipients (separated by [median (IQR)] 6 (3–8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p <.01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291–15 417] vs. 6442 [5156–7639] IEQ/kg; p <.0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta −0.35; p =.02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.

Original languageEnglish
Pages (from-to)154-164
Number of pages11
JournalAmerican Journal of Transplantation
Volume22
Issue number1
Early online date22 Aug 2021
DOIs
Publication statusPublished - Jan 2022

Keywords

  • clinical research/practice
  • diabetes: type 1
  • endocrinology/diabetology
  • graft survival
  • islet isolation
  • islet transplantation

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