Five-Year Metabolic, Functional, and Safety Results of Patients With Type 1 Diabetes Transplanted With Allogenic Islets Within the Swiss-French GRAGIL Network

Abstract

OBJECTIVETo describe the 5-year outcomes of islet transplantation within the Swiss-French GRAGIL Network. RESEARCH DESIGN AND METHODSRetrospective analysis of all subjects enrolled in the GRAGIL-1c and GRAGIL-2 islet transplantation trials. Parameters related to metabolic control, graft function, and safety outcomes were studied. Recipients received a total islet mass of 9,715.75 6 3,444.40 IEQ/kg. Thirty-four patients completed a 5-year follow-up, and 10 patients completed a 4-year follow-up. At 1, 4, and 5 years after islet transplantation, respectively, 83%, 67%, and 58% of the ITA recipients and 80%, 70%, and 60% of the IAK transplant recipients reached HbA 1c under 7% (53 mmol/mol) and were free of severe hypoglycemia, while none of the ITA recipients and only 10% of the IAK transplant recipients met this composite criterion at the preinfusion stage. Thirty-three of 44 patients (75%) experienced insulin independence during the entire follow-up period, with a median duration of insulin independence of 19.25 months (interquartile range 2-58). Twenty-nine of 44 recipients (66%) exhibited at least one adverse event; 18 of 55 adverse events (33%) were possibly related to immunosuppression; and complications related to the islet infusion (n = 84) occurred in 10 recipients (11.9%). RESULTS Forty CONCLUSIONSIn a large cohort with a 5-year follow-up and in a multicenter network setting, islet transplantation was safe and efficient in restoring good and lasting glycemic control and preventing severe hypoglycemia in patients with type 1 diabetes.Over the last decade, islet transplantation has emerged as a promising treatment for type 1 diabetes. Currently, islet transplantation can be offered to patients with type 1 diabetes who are experiencing major glucose variability and lack of predictability and unawareness of hypoglycemic episodes despite intensive insulin therapy and

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression

“…is in line with the results of other groups (2,4,8,(17)(18)(19)(20)(21)(22)(23) which studied more heterogeneous groups of isletalone and islet-after-kidney transplantation recipients and/or using different immune suppression regimens.…”

“…This is not easy in view of the heterogeneity of the recipients and in the transplant protocols. Single center protocols usually have standardized follow-up of graft function, metabolic control and safety outcome measurements (2,(4)(5)(6)(7).…”

“…For type 1 diabetic patients with problematic hypoglycemia, islet transplantation represents a possibility of therapy (1)(2)(3). However, the risk benefit ratio needs to be determined.…”

Beta-cell replacement therapy

“…This success rides on the shoulders of the gains made in islet isolation and improved immunosuppressive regimens [4][5][6]15 && ,62, 67,68]. Together, these advances should potentiate improved long-term outcomes and help to decrease the need for multiple pancreata to achieve a therapeutic cell mass.…”

Combined Pancreatic Islet-Lung-Liver Transplantation in a Pediatric Patient with Cystic Fibrosis-Related Diabetes

“…After these, insulin could be reduced and HbA1c indicated improved glycemic control. Still, exogenous insulin could not be stopped despite conditions usually compatible with insulin independence for type 1 diabetic patients after IT [13]: a total of approximately 31,000 transplanted IEQ/kg and excellent basal and arginine-stimulated C-peptide levels. The patient’s course was remarkable for very high needs in insulin: before the transplants, his mean daily insulin needs were higher than commonly reported for CFRD [14].…”