King's College London

TY - JOUR

T1 - The impact of islet mass, number of transplants, and time between transplants on graft function in a national islet transplant program

AU - Forbes, Shareen

AU - Flatt, Anneliese J.

AU - Bennett, Denise

AU - Crookston, Robert

AU - Pimkova, Mirka

AU - Birtles, Linda

AU - Pernet, Andrew

AU - Wood, Ruth C.

AU - Burling, Keith

AU - Barker, Peter

AU - Counter, Claire

AU - Lumb, Alistair

AU - Choudhary, Pratik

AU - Rutter, Martin K.

AU - Rosenthal, Miranda

AU - Sutherland, Andrew

AU - Casey, John

AU - Johnson, Paul

AU - Shaw, James A.M.

N1 - Funding Information: SF contributed to study design and performed all data analysis, interpreted data and wrote the first draft of the manuscript; AF contributed to data collection and manuscript drafting. JAMS contributed to study design and data interpretation. CC undertook longer term graft survival analysis. The study was interpreted by all authors and all authors commented on and approved the final version of the manuscript. SF is the guarantor of this work and, as such, had full access to all study data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors thank the Study Manager Cath Brennand and Data Manager Ruth Wood, in addition to the many surgeons, physicians, research nurses, transplant coordinators, and clinical research associates at all sites who contributed to data collection. Donor data were obtained from the UK Transplant Registry and analysed by NHSBT Statistics and Clinical Audit, Bristol, UK. C-peptide and glucose assays were performed by the NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay Laboratory. The UK islet transplant program is funded by the National Health Service National Commissioning Group. The current study was funded by the Diabetes UK Grant: Biomedical and Psychosocial Outcomes of Islet Transplantation BDA 06/0003362. Funding Information: SF contributed to study design and performed all data analysis, interpreted data and wrote the first draft of the manuscript; AF contributed to data collection and manuscript drafting. JAMS contributed to study design and data interpretation. CC undertook longer term graft survival analysis. The study was interpreted by all authors and all authors commented on and approved the final version of the manuscript. SF is the guarantor of this work and, as such, had full access to all study data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors thank the Study Manager Cath Brennand and Data Manager Ruth Wood, in addition to the many surgeons, physicians, research nurses, transplant coordinators, and clinical research associates at all sites who contributed to data collection. Donor data were obtained from the UK Transplant Registry and analysed by NHSBT Statistics and Clinical Audit, Bristol, UK. C‐peptide and glucose assays were performed by the NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay Laboratory. The UK islet transplant program is funded by the National Health Service National Commissioning Group. The current study was funded by the Diabetes UK Grant: Biomedical and Psychosocial Outcomes of Islet Transplantation BDA 06/0003362. Publisher Copyright: © 2021 The Authors. American Journal of Transplantation published by Wiley periodicals LLC on behalf of the The American Society of Transplantation and the American Society of Transplant Surgeons.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

KW - clinical research/practice

KW - diabetes: type 1

KW - endocrinology/diabetology

KW - graft survival

KW - islet isolation

KW - islet transplantation

UR - http://www.scopus.com/inward/record.url?scp=85113233394&partnerID=8YFLogxK

U2 - 10.1111/ajt.16785

DO - 10.1111/ajt.16785

M3 - Article

AN - SCOPUS:85113233394

VL - 22

SP - 154

EP - 164

JO - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

SN - 1600-6135

IS - 1

ER -