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Recurrence of Type 1 Diabetes Mellitus

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Transplantation of the Pancreas

Abstract

Simultaneous pancreas–kidney (SPK) transplantation is the best option for patients with type 1 diabetes (T1D) and end-stage kidney (ESKD) disease. While most SPK recipients experience long-term euglycemia, about 5% experience T1D recurrence (T1DR), and return to insulin therapy 5–20 years after transplantation. Since the identification of our first patient with T1DR two decades ago, we have assessed autoimmunity in our patients. This includes evaluating T1D-associated autoantibodies (GAD65, IA2 and ZnT8), autoreactive T cells against islet antigens, and pancreas transplant (PT) biopsies. We have shown that most patients with T1DR experience sero-conversion for multiple autoantibodies. In addition, autoreactive memory T cells have been identified in the peripheral blood, PT, and peri-PT lymph nodes. PT biopsies generally exhibit insulitis, the typical lesion of T1D, affecting pancreatic islets in the PT. Somewhat surprisingly, PT biopsies may show considerable insulin staining in the beta islet cells, and mixed meal tolerance tests may demonstrate persistent c-peptide secretion, despite the clinical presentation with severe hyperglycemia. This has led to attempts to treat our patients with T1DR. This chapter describes therapeutic efforts, as well as projections for the future, along with our hope that this will translate to possible treatment for T1D.

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Abbreviations

ESKD:

End-stage kidney disease

H&E:

Hematoxylin and eosin

IGRP:

Islet-specific glucose-6-phosphatase catalytic subunit-related protein

IVIg:

Intravenous immunoglobulin

MMTT:

Mixed meal tolerance test

PB:

Peripheral blood

SPK:

Simultaneous pancreas–kidney

SPKT:

Simultaneous pancreas–kidney transplant

T1D:

Type 1 diabetes

T1DR:

Type 1 diabetes recurrence

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Authors and Affiliations

  1. Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, USA

    George W. Burke III, Gaetano Ciancio, Mahmoud Morsi, Jose Figueiro & Linda Chen

  2. Division of Kidney-Pancreas Transplantation, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

    George W. Burke III, Gaetano Ciancio, Mahmoud Morsi, Jose Figueiro & Linda Chen

  3. Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA

    George W. Burke III & Alberto Pugliese

  4. Division of Endocrinology, Department of Medicine, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, FL, USA

    Junichiro Sageshima & Francesco Vendrame

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  1. George W. Burke III
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  2. Gaetano Ciancio
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  4. Jose Figueiro
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  5. Linda Chen
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  6. Junichiro Sageshima
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  7. Francesco Vendrame
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  8. Alberto Pugliese
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Correspondence to George W. Burke III .

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Editors and Affiliations

  1. Department of Surgery, State University of New York (SUNY), Downstate Health Sciences University, Brooklyn, NY, USA

    Rainer W. G. Gruessner

  2. Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA

    Angelika C. Gruessner

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Burke, G.W. et al. (2023). Recurrence of Type 1 Diabetes Mellitus. In: Gruessner, R.W.G., Gruessner, A.C. (eds) Transplantation of the Pancreas. Springer, Cham. https://doi.org/10.1007/978-3-031-20999-4_56

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