Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study

• Published in: Diabetes care Vol. 42; no. 11; pp. 2042 - 2049
• Main Authors: Vantyghem, Marie-Christine, Chetboun, Mikael, Gmyr, Valéry, Jannin, Arnaud, Espiard, Stéphanie, Le Mapihan, Kristell, Raverdy, Violeta, Delalleau, Nathalie, Machuron, François, Hubert, Thomas, Frimat, Marie, Van Belle, Eric, Hazzan, Marc, Pigny, Pascal, Noel, Christian, Caiazzo, Robert, Kerr-Conte, Julie, Pattou, François
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.11.2019
• Subjects: Antibodies; Blood Glucose / metabolism; Cohort analysis; Combined Modality Therapy; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 / blood; Grafting; Hypoglycemia; Immunosuppression; Insulin; Interleukin 2; Interleukins; Islet cells; Kidney transplantation; Kidney transplants; Life Sciences; Metabolism; Pancreatic islet transplantation; Rapamycin; Renal function; Research design; Tacrolimus; Transplantation
• ISSN: 0149-5992; 1935-5548; 1935-5548; 0149-5992
• DOI: 10.2337/dc19-0401

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. 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. 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. 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.