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

Research output: Contribution to journalArticle

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 1 2019

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Pancreatectomy
Glutamate Decarboxylase
Autologous Transplantation
Chronic Pancreatitis
Antibodies
Insulin
Transplants
Type 1 Diabetes Mellitus
Diabetes Mellitus
C-Peptide
Autoimmunity
Islets of Langerhans

Keywords

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

PubMed: MeSH publication types

  • Journal Article

Cite this

@article{5dc63ed39a4847eda57d9677615dcd98,
title = "The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation",
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.",
keywords = "Autoimmune, Chronic pancreatitis, Diabetes mellitus, Glutamic acid decarboxylase, Islet auto-transplantation",
author = "M. Kizilgul and Wilhelm, {J. J.} and Dunn, {Ty B} and Beilman, {Gregory J} and Pruett, {Timothy L} and Srinath Chinnakotla and Khalid Amin and Hering, {Bernhard J} and Bellin, {Melena D}",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.diabet.2018.01.001",
language = "English (US)",
volume = "45",
pages = "301--305",
journal = "Diabetes and Metabolism",
issn = "0338-1684",
publisher = "Elsevier Masson",
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TY - JOUR

T1 - The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation

AU - Kizilgul, M.

AU - Wilhelm, J. J.

AU - Dunn, Ty B

AU - Beilman, Gregory J

AU - Pruett, Timothy L

AU - Chinnakotla, Srinath

AU - Amin, Khalid

AU - Hering, Bernhard J

AU - Bellin, Melena D

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - Autoimmune

KW - Chronic pancreatitis

KW - Diabetes mellitus

KW - Glutamic acid decarboxylase

KW - Islet auto-transplantation

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U2 - 10.1016/j.diabet.2018.01.001

DO - 10.1016/j.diabet.2018.01.001

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VL - 45

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JO - Diabetes and Metabolism

JF - Diabetes and Metabolism

SN - 0338-1684

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