Marie-Christine Vantyghem1,2,3, Mikael Chetboun4,3,5, Valéry Gmyr4,3, Arnaud Jannin2, Stéphanie Espiard2, Kristell Le Mapihan2, Violeta Raverdy4,3, Nathalie Delalleau4,3, François Machuron6, Thomas Hubert4,3, Marie Frimat7, Eric Van Belle8, Marc Hazzan7, Pascal Pigny9, Christian Noel7, Robert Caiazzo4,3,5, Julie Kerr-Conte4,3, François Pattou1,3,5. 1. University of Lille, U1190-EGID, Lille, France mc-vantyghem@chru-lille.fr francois.pattou@univ-lille.fr. 2. Department of Endocrinology, Diabetology, and Metabolism, Centre Hospitalier Universitaire de Lille, Lille, France. 3. Inserm, U1190, Lille, France. 4. University of Lille, U1190-EGID, Lille, France. 5. Department of General and Endocrine Surgery, Centre Hospitalier Universitaire de Lille, Lille, France. 6. Department of Methodology, Biostatistics, and Data Management, Centre Hospitalier Universitaire de Lille, Lille, France. 7. Department of Nephrology, Centre Hospitalier Universitaire de Lille, Lille, France. 8. Department of Cardiology, Centre Hospitalier Universitaire de Lille, Lille, France. 9. Department of Biochemistry and Hormonology, Centre Hospitalier Universitaire de Lille, Lille, France.
Abstract
OBJECTIVE: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. RESEARCH DESIGN AND METHODS: We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43-92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function. RESULTS: The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22-57) and 28% (13-45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62-92) and 78% (57-89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence. CONCLUSIONS: Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not.
OBJECTIVE: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. RESEARCH DESIGN AND METHODS: We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43-92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function. RESULTS: The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22-57) and 28% (13-45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62-92) and 78% (57-89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence. CONCLUSIONS: Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not.
Authors: Barry McDermott; Scott Robinson; Sven Holcombe; Ruth E Levey; Peter Dockery; Paul Johnson; Stewart Wang; Eimear B Dolan; Garry P Duffy Journal: J R Soc Interface Date: 2021-12-22 Impact factor: 4.118
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Authors: Aleksandra Kukla; Pedro Ventura-Aguiar; Matthew Cooper; Eelco J P de Koning; David J Goodman; Paul R Johnson; Duck J Han; Didier A Mandelbrot; Martha Pavlakis; Frantisek Saudek; Marie-Christine Vantyghem; Titus Augustine; Michael R Rickels Journal: Am J Kidney Dis Date: 2021-05-14 Impact factor: 11.072
Authors: 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 Journal: Am J Transplant Date: 2021-08-22 Impact factor: 9.369