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Presenter: Shareen, Forbes, Edinburgh, United Kingdom
Authors: Shareen Forbes, Anneliese Flatt, Rob Crookston, Pratik Choudhary, Martin K Rutter, Miranda Rosenthal, John Casey, Paul Johnson, James Shaw
S. Forbes1,7, A. Flatt2,7, R. Crookston3,7, P. Choudhary4,7, M. Rutter5,7, M. Rosenthal6,7, J. Casey1,7, P. Johnson3,7, J. Shaw2,7.
1Transplant and Diabetes, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh,UK, ; 2Institute of Transplantation, Freeman Hospital, Newcastle, UK, ; 3Nuffield Department ofvSurgical Sciences, John Radcliffe Hospital, Oxford, UK, ; 4Department of Diabetes, Kings College Hospital, London, UK, ; 5Manchester Diabetes Centre , Manchester Royal Infirmary, Manchester, UK, ; 6Diabetes Department, Royal Free Hospital, London, UK, ; 7UKITC,
Aim: Pancreata for the NHS islet transplant programme (comprising 7 transplant centres / 3 isolation facilities) are provided through the National Pancreas Allocation Scheme. Donation after brain death (DBD) and donation after cardiac death (DCD) pancreata are allocated for first graft followed by the potential for ‘priority listing’ towards provision of a second graft within 12 months. We aimed to determine the relationships of transplant mass and time between first and second graft to 12-month graft function in the UK islet transplant cohort with Type 1 diabetes complicated by recurrent severe hypoglycaemia.
Methods: All patients transplanted since programme inception in April 2008 and before April 2015 with 12 month post-first transplant data were included. Recipients who had experienced graft failure over this period and those not consenting to research were excluded from analyses. Graft function was assessed by 90-minute stimulated C-peptide in a standard mixed meal tolerance test and the BETA-2 score at 12 months. The cumulative number of IEQ/kg for each recipient was adjusted for time between transplants in those subjects receiving 2 transplants (<3 months versus ≥3 months and ≥6 months) in a series of multiple regression analyses. In separate analyses baseline and 12-month rates of severe hypoglycaemia, HbA1c and insulin dose were compared in the whole group.
Results: Four recipients did not provide research consent and nine experienced graft failure (stimulated C-peptide <50 pmol/L) after (median (IQR)) 5 (3-6) months. 82 participants (73 (89%) islet transplant alone / 9 (11%) islet after kidney; 49 (60%) female; weight 67 (61-79) kg; BMI 25.3(22.4-27.6) kg/m2) received 133 transplants with uninterrupted graft function over the first 12 months.
31 recipients had a single infusion and 51 had two infusions separated by 6.2 (3.1-7.5) months- 12 subjects (24%) within 3 months, 12 (24%) within 3-6 months and 27 (53%) ≥6 months following the first.
Total transplanted mass was 6138 (5183-8345) IEQ/kg in single transplant recipients vs. 11202 (8972-14642) IEQ/kg (p<0.001) in recipients receiving two transplants. At 12 months post-first transplant, 90-minute stimulated C-peptide was 570 (209-884) pmol/L with BETA-2 score 8 (4-14). Baseline versus 12-month severe hypoglycaemia rate was 15 (4-50) vs. 0 (0-0) episodes/patient/year (p<0.001); HbA1c: 67 (56-81) vs. 48 (42-55) mmol/mol (p<0.001); and total daily insulin dose: 0.52 (0.41-0.63) vs. 0.24 (0.07-0.39) units/kg (p<0.001).
Total transplant mass was associated with the BETA-2 score in univariate linear regression (β=0.24; p=0.03). There was a positive association between the BETA-2 score and time between 1st and 2nd transplants <3 months (β=+0.11; p=0.36) and a negative association between the BETA-2 score and time between 1st and 2nd transplants ≥3 and ≥6 months (all p>0.05).
Islet mass following one transplant and islet mass adjusted for a second islet transplant <3 months following the first was positively associated with the BETA-2 score (p<0.05) whereas islet mass adjusted for a second islet transplant ≥6 months failed to reach statistical significance (β=+0.24; p=0.052).
Conclusion: Clinical benefit has been confirmed at 12 months following one or two islet transplants. Graft function was associated with total graft mass in addition to time between transplants. The National Allocation Scheme has recently been revised with the goal of shortening median time to priority second graft from 6 to 3 months.
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