Prolonged Insulin Independence After Islet Allotransplants in Recipients with Type 1 Diabetes

We sought to determine the long‐term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received one to two islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus et...

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Bibliographic Details
Published in:American journal of transplantation 2008-11, Vol.8 (11), p.2463-2470
Main Authors: Bellin, M. D., Kandaswamy, R., Parkey, J., Zhang, H.‐J., Liu, B., Ihm, S. H., Ansite, J. D., Witson, J., Bansal‐Pakala, P., Balamurugan, A. N., Papas, K., Sutherland, D. E. R., Moran, A., Hering, B. J.
Format: Article
Language:English
Subjects:
Adult
Allograft survival
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antilymphocyte Serum - therapeutic use
Biological and medical sciences
Cyclosporine - therapeutic use
Diabetes Mellitus, Type 1 - therapy
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etanercept
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Everolimus
Female
Humans
Immunoglobulin G - therapeutic use
Immunosuppressive Agents - therapeutic use
Insulin - metabolism
islet graft
islet transplantation
islets
Islets of Langerhans - cytology
Islets of Langerhans Transplantation - methods
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Receptors, Tumor Necrosis Factor - therapeutic use
Recurrence
Sirolimus - analogs & derivatives
Sirolimus - therapeutic use
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
thymoglobulin
Treatment Outcome
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary:We sought to determine the long‐term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received one to two islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor‐α blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 ± 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A1c levels and C‐peptide production) and for adverse events associated with the study protocol. Of the six recipients, five were insulin‐independent at 1 year, and four continue to be insulin‐independent at a mean of 3.4 ± 0.4 years posttransplant. None of the six recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 ± 21.2 mL/min/1.73 m2 pretransplant to 82.6 ±19.1 mL/min/1.73 m2 at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of >3 years in four of six recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long‐term graft survival. In 4 of 6 type 1 diabetic islet allotransplant recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance, insulin independence was maintained for a mean of >3 years.
ISSN:1600-6135
1600-6143
DOI:10.1111/j.1600-6143.2008.02404.x