The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation
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 t...
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| Veröffentlicht in: | Diabetes & metabolism 2019-06, Vol.45 (3), p.301-305 |
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| creator | Kizilgul, M. Wilhelm, J.J. Dunn, T.B. Beilman, G.J. Pruett, T.L. Chinnakotla, S. Amin, K. Hering, B.J. Bellin, M.D. |
| description | 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.
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.
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 |
| doi_str_mv | 10.1016/j.diabet.2018.01.001 |
| format | Article |
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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.
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%.
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.</description><identifier>ISSN: 1262-3636</identifier><identifier>EISSN: 1878-1780</identifier><identifier>DOI: 10.1016/j.diabet.2018.01.001</identifier><identifier>PMID: 29395812</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Adult ; Autoantibodies ; Autoimmune ; Chronic pancreatitis ; Diabetes mellitus ; Diabetes Mellitus, Type 1 - immunology ; Diabetes Mellitus, Type 1 - surgery ; Female ; Glutamate Decarboxylase - immunology ; Glutamic acid decarboxylase ; Humans ; Islet auto-transplantation ; Islets of Langerhans Transplantation - methods ; Male ; Middle Aged ; Pancreatectomy - methods ; Pancreatitis, Chronic - immunology ; Pancreatitis, Chronic - surgery ; Prognosis ; Transplantation, Autologous ; Young Adult</subject><ispartof>Diabetes & metabolism, 2019-06, Vol.45 (3), p.301-305</ispartof><rights>2018 Elsevier Masson SAS</rights><rights>Copyright © 2018 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-b8ee88334708b1bd9a3c9f2a1c22ce239986c113787515da4e2498dbc6c20a213</citedby><cites>FETCH-LOGICAL-c362t-b8ee88334708b1bd9a3c9f2a1c22ce239986c113787515da4e2498dbc6c20a213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S126236361830003X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29395812$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kizilgul, M.</creatorcontrib><creatorcontrib>Wilhelm, J.J.</creatorcontrib><creatorcontrib>Dunn, T.B.</creatorcontrib><creatorcontrib>Beilman, G.J.</creatorcontrib><creatorcontrib>Pruett, T.L.</creatorcontrib><creatorcontrib>Chinnakotla, S.</creatorcontrib><creatorcontrib>Amin, K.</creatorcontrib><creatorcontrib>Hering, B.J.</creatorcontrib><creatorcontrib>Bellin, M.D.</creatorcontrib><title>The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation</title><title>Diabetes & metabolism</title><addtitle>Diabetes Metab</addtitle><description>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.
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.
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%.
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.</description><subject>Adult</subject><subject>Autoantibodies</subject><subject>Autoimmune</subject><subject>Chronic pancreatitis</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Diabetes Mellitus, Type 1 - surgery</subject><subject>Female</subject><subject>Glutamate Decarboxylase - immunology</subject><subject>Glutamic acid decarboxylase</subject><subject>Humans</subject><subject>Islet auto-transplantation</subject><subject>Islets of Langerhans Transplantation - methods</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pancreatectomy - methods</subject><subject>Pancreatitis, Chronic - immunology</subject><subject>Pancreatitis, Chronic - surgery</subject><subject>Prognosis</subject><subject>Transplantation, Autologous</subject><subject>Young Adult</subject><issn>1262-3636</issn><issn>1878-1780</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu1TAUjBAVLYU_QMhLNgl-5OFskFDFo1Klbtq15dgnub5K7GA70PtL_UpOldIlq2NpZs4czxTFB0YrRln7-VhZpwfIFadMVpRVlLJXxQWTnSxZJ-lrfPOWl6IV7XnxNqUjEngv5JviHEffSMYvise7A5A1hsmHlJ0hyU3ejc5ob4CEkUzzlvWCgDbOEgtGxyE8nGadgGif3RCsg0ScJ6vODnxO5I_LB2IOMXiUrbgoAkLZJbJ5C3EKzk8kh6znFxRMDstpV7o0QyZ6Q0bUPq0z2qA--HfF2ajnBO-f52Vx__3b3dXP8ub2x_XV15vSiJbncpAAUgpRd1QObLC9FqYfuWaGcwNc9L1sDWOik13DGqtr4HUv7WBaw6nmTFwWn_a9GMuvDVJWi0sGZjwEwpYU6zG9vm6bBqn1TjUxpBRhVGt0i44nxah6akkd1d6SempJUaawBJR9fHbYhgXsi-hfLUj4shMA__nbQVTJYLgGrIuYlbLB_d_hL_enquU</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>Kizilgul, M.</creator><creator>Wilhelm, J.J.</creator><creator>Dunn, T.B.</creator><creator>Beilman, G.J.</creator><creator>Pruett, T.L.</creator><creator>Chinnakotla, S.</creator><creator>Amin, K.</creator><creator>Hering, B.J.</creator><creator>Bellin, M.D.</creator><general>Elsevier Masson SAS</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201906</creationdate><title>The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation</title><author>Kizilgul, M. ; Wilhelm, J.J. ; Dunn, T.B. ; Beilman, G.J. ; Pruett, T.L. ; Chinnakotla, S. ; Amin, K. ; Hering, B.J. ; Bellin, M.D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-b8ee88334708b1bd9a3c9f2a1c22ce239986c113787515da4e2498dbc6c20a213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Autoantibodies</topic><topic>Autoimmune</topic><topic>Chronic pancreatitis</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Diabetes Mellitus, Type 1 - surgery</topic><topic>Female</topic><topic>Glutamate Decarboxylase - immunology</topic><topic>Glutamic acid decarboxylase</topic><topic>Humans</topic><topic>Islet auto-transplantation</topic><topic>Islets of Langerhans Transplantation - methods</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pancreatectomy - methods</topic><topic>Pancreatitis, Chronic - immunology</topic><topic>Pancreatitis, Chronic - surgery</topic><topic>Prognosis</topic><topic>Transplantation, Autologous</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kizilgul, M.</creatorcontrib><creatorcontrib>Wilhelm, J.J.</creatorcontrib><creatorcontrib>Dunn, T.B.</creatorcontrib><creatorcontrib>Beilman, G.J.</creatorcontrib><creatorcontrib>Pruett, T.L.</creatorcontrib><creatorcontrib>Chinnakotla, S.</creatorcontrib><creatorcontrib>Amin, K.</creatorcontrib><creatorcontrib>Hering, B.J.</creatorcontrib><creatorcontrib>Bellin, M.D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kizilgul, M.</au><au>Wilhelm, J.J.</au><au>Dunn, T.B.</au><au>Beilman, G.J.</au><au>Pruett, T.L.</au><au>Chinnakotla, S.</au><au>Amin, K.</au><au>Hering, B.J.</au><au>Bellin, M.D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation</atitle><jtitle>Diabetes & metabolism</jtitle><addtitle>Diabetes Metab</addtitle><date>2019-06</date><risdate>2019</risdate><volume>45</volume><issue>3</issue><spage>301</spage><epage>305</epage><pages>301-305</pages><issn>1262-3636</issn><eissn>1878-1780</eissn><abstract>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.
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.
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%.
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.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>29395812</pmid><doi>10.1016/j.diabet.2018.01.001</doi><tpages>5</tpages></addata></record> |
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| ispartof | Diabetes & metabolism, 2019-06, Vol.45 (3), p.301-305 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Adult Autoantibodies Autoimmune Chronic pancreatitis Diabetes mellitus Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - surgery Female Glutamate Decarboxylase - immunology Glutamic acid decarboxylase Humans Islet auto-transplantation Islets of Langerhans Transplantation - methods Male Middle Aged Pancreatectomy - methods Pancreatitis, Chronic - immunology Pancreatitis, Chronic - surgery Prognosis Transplantation, Autologous Young Adult |
| title | The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation |
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