Islets of Langerhans Transplantation, Type 1 Diabetes (T1D)
Conditions
Keywords
islet transplantation, pancreas transplantation, type 1 diabetes, beta cell replacement, graft survival, glycemic control
Brief summary
Islet transplantation and pancreas transplantation are established therapeutic options for selected individuals with type 1 diabetes experiencing severe glycemic instability and recurrent hypoglycemia. Although these approaches significantly improve glycemic management and quality of life, long-term graft survival remains limited, with a progressive decline in beta-cell function over time. The clinical benefit-risk profile of islet re-transplantation after graft failure remains poorly defined, and outcomes following repeat islet transplantation after prior islet graft failure have not been specifically evaluated. Repeated exposure to multiple donors may increase the risk of alloimmunization, including the development of donor-specific antibodies , which may adversely affect graft survival and limit access to future transplantation. This multicenter retrospective cohort study aims to evaluate the efficacy and safety of islet re-transplantation in adults with type 1 diabetes after failure of initial beta-cell replacement (islet or pancreas transplantation), with outcomes assessed at 3 months, 1 year, and 5 years.
Interventions
None listed
Sponsors
University Hospital, Montpellier
University Hospital, Grenoble
University Hospital, Toulouse
University Hospital, Strasbourg
University Hospital, Lille
University Hospital, Paris
The Civil Hospitals, Lyon
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosis of type 1 diabetes * Prior beta-cell replacement therapy : islet transplantation or pancreas transplantation * Islet re-transplantation performed after 2005 * Islet re-transplantation performed after documented beta cell graft failure, defined by undetectable C-peptide and/or recurrence of severe hypoglycemia on insulin therapy * Availability of clinical and biological data required for assessment of study outcomes
Exclusion criteria
* Missing or incomplete data preventing assessment of the primary outcome * Patients who did not meet inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Islet graft success | Baseline, 3 months, 1 year, 5 years | Assessed using Igls criteria (optimal or good graft function classification) based on C-peptide, insulin use, hemoglobin A1c, and severe hypoglycemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Control_Glycated hemoglobin (HbA1c) level | Baseline, 3 months, 1 year, 5 years | HbA1c level, measured by HPLC method |
| Glycemic Control_Percentage of individuals with HbA1c < 7% and no severe hypoglycemia | Baseline, 3 months, 12 months, 5 years | — |
| Beta-Cell Function_BETA-2 score | Baseline, 3 months, 1 year, 5 years | Derived from fasting glucose, paired fasting C-peptide, insulin dose and Hba1c and generates a single value between 0 and 42 |
| Beta-Cell Function_BETA score | Baseline, 3 months, 1 year, 5 years | Derived from fasting glucose, HbA1c, stimulated C-peptide, and absence of insulin or oral hypoglycemic agent use and generates a single value between 0 and 8 |
| Beta-Cell Function_Severe hypoglycemia events | Baseline, 3 months, 1 year, 5 years | Percentage of individual with severe hypoglycemia events |
| Beta-Cell Function_Residual beta cell function | Baseline, 3 months, 1 year, 5 years | Percentage of individual with fasting plasma C-peptide \> 0.3 ng/mL |
| Immunological Outcomes_Donor-specific antibodies (DSA) | Baseline, 3 months, 1 year, 5 years | Presence and specificity of donor-specific antibodies (DSA) with classification : * Preformed and de novo * Class I and II specificity * and Mean fluorescence intensity (MFI) |
| Immunological Outcomes_Autoantibodies | Baseline, 3 months, 1 year, 5 years | Dosage of antibodies anti-GAD, anti-IA2, anti-insulin, and anti-ZnT8 |
| Safety of islet re-transplantation_Procedural complications of islet infusions | Baseline, 3 months, 1 year, 5 years | Reported of procedural complications of islet infusions such as portal thrombosis, hematoma, transfusion requirement |
| Safety of islet re-transplantation_Renal function eGFR | Baseline, 3 months, 1 year, 5 years | Estimated GFR from serum creatinine level |
| Safety of islet re-transplantation_Albuminuria | Baseline, 3 months, 1 year, 5 years | Measurement of albuminuria or proteinuria |
| Safety of islet re-transplantation_Immunosuppression-related complications | 3 months, 1 year, 5 years | Reported immunosuppression-related complications such as infections ; malignancy, cardiovascular events |
| Safety of islet re-transplantation_Mortality | 3 months, 1 year, 5 years | Patient death |
Countries
France
Contacts
CONTACTOrianne OV Villard, MD
CONTACTRoxane RD Descaillot
Outcome results
None listed