The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation

M. Kizilgul, J. J. Wilhelm, T. B. Dunn, G. J. Beilman, T. L. Pruett, S. Chinnakotla, K. Amin, B. J. Hering, M. D. Bellin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

AIM: Islet autotransplantation (IAT) is considered a 'non-immune' model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT.

METHODS: We identified 9 patients undergoing TPIAT with elevated GADA pre-TPIAT (8 non-diabetic and 1 with C-peptide positive DM), otherwise demographically similar to GADA negative TPIAT recipients (n=341). Metabolic and clinical measures related to islet cell function were recorded both before and after TPIAT.

RESULTS: None of the 9 TPIAT patients achieved insulin independence after surgery, vs. 33% of GADA negative patients (n=318 with 1-yr follow-up). The two patients with the highest titters of GADA (>250 IU/mL) both experienced islet graft failure, despite normoglycaemia pre-TPIAT and high islet mass transplanted (5276 and 9378 IEQ per kg), with elevated HbA1c levels post-TPIAT (8.3%, 9.6%). The remaining 7 seven were insulin dependent with partial graft function and HbA1c levels <7%.

CONCLUSION: Insulin dependence was more frequent in 9 patients with elevated GADA prior to TPIAT than in GADA negative TPIAT recipients, with graft failure in 2 cases. We speculate that beta-cell autoimmunity may occur in a small subset of TPIAT recipients and that beta cell antibody testing prior to TPIAT may be warranted to identify individuals at higher risk for insulin dependence.

Original languageEnglish (US)
Pages (from-to)301-305
Number of pages5
JournalDiabetes and Metabolism
Volume45
Issue number3
DOIs
StatePublished - Jun 2019

Bibliographical note

Funding Information:
We are incredibly grateful to the islet manufacturing and clinical care teams that are instrumental to the success of the TPIAT program at our institution, with special thanks to Muhamad Abdulla, David Heller, Tom Gilmore, Zach Swanson, Jacob Ricks, Louise Berry, and Marie Cook. Muhammed Kizilgul was supported by a grant from The Scientific and Technical Research Council of Turkey (TUBITAK).

Publisher Copyright:
© 2018 Elsevier Masson SAS

Keywords

  • Autoimmune
  • Chronic pancreatitis
  • Diabetes mellitus
  • Glutamic acid decarboxylase
  • Islet auto-transplantation

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