Recurrence of immunological markers for type 1 (insulin-dependent) diabetes mellitus in immunosuppressed patients after pancreas transplantation

Abstract

Background: Type 1 (insulin dependent) diabetes mellitus (IDDM) is an autoimmune disease in which autoantibodies against islet cells develop concomitantly with or even preceding diagnosis. Because the recurrence of diabetes can be the cause of graft failure in patients with pancreas transplantation, we studied the possible recurrence of IDDM immunomarkers after transplantation.

Methods: The following determinations were performed every 1-2 years after transplantation in 50 immunosuppressed IDDM patients with simultaneous kidney and pancreas transplantation (bladder drainage of exocrine secretion): islet cell antibodies (ICA) by direct immunofluorescence, antibodies against glutamic acid decarboxylase (GADab) by radiobinding assay, and the oral glucose tolerance test. The mean follow-up was 4.1+/-6.3 (range 1 to 9 years).

Results: GADab were detected in 11 patients after transplantation, 10 of whom had been positive beforehand. ICA reappearance after transplantation was detected in seven patients (14%). The presence of ICA was related to GADab positivity (P=0.001) and HLA DR3 patients (P=0.04), but not with pancreatitis and rejection episodes, immunosuppression induction therapy, or donor HLA haplotype. During follow-up, an abnormal oral glucose tolerance test was more frequent in ICA-positive patients (P=0.02), with no differences in metabolic control or insulin secretion.

Conclusion: We conclude that GADab persist and ICA reappear despite immunosuppressive therapy in patients with functioning pancreas transplants. The relevance and the risk that this implies for IDDM development should be determined.