Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients
The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-y...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Transplant International |
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| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/ti.2024.12320/full |
| _version_ | 1797221072903340032 |
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| author | Tasneem R. Abdel-Karim James S. Hodges Kevan C. Herold Timothy L. Pruett Karthik V. Ramanathan Bernhard J. Hering Ty B. Dunn Ty B. Dunn Varvara A. Kirchner Varvara A. Kirchner Gregory J. Beilman Melena D. Bellin Melena D. Bellin |
| author_facet | Tasneem R. Abdel-Karim James S. Hodges Kevan C. Herold Timothy L. Pruett Karthik V. Ramanathan Bernhard J. Hering Ty B. Dunn Ty B. Dunn Varvara A. Kirchner Varvara A. Kirchner Gregory J. Beilman Melena D. Bellin Melena D. Bellin |
| author_sort | Tasneem R. Abdel-Karim |
| collection | DOAJ |
| description | The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period. |
| first_indexed | 2024-04-24T12:59:38Z |
| format | Article |
| id | doaj.art-59a5c9a352c64d349d9c0a3738f741f5 |
| institution | Directory Open Access Journal |
| issn | 1432-2277 |
| language | English |
| last_indexed | 2024-04-24T12:59:38Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| spelling | doaj.art-59a5c9a352c64d349d9c0a3738f741f52024-04-05T16:19:55ZengFrontiers Media S.A.Transplant International1432-22772024-01-013710.3389/ti.2024.1232012320Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant RecipientsTasneem R. Abdel-Karim0James S. Hodges1Kevan C. Herold2Timothy L. Pruett3Karthik V. Ramanathan4Bernhard J. Hering5Ty B. Dunn6Ty B. Dunn7Varvara A. Kirchner8Varvara A. Kirchner9Gregory J. Beilman10Melena D. Bellin11Melena D. Bellin12Department of Pediatrics, University of Minnesota, Minneapolis, MN, United StatesDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United StatesDepartments of Immunobiology and Internal Medicine, Yale University, New Haven, CT, United StatesDepartment of Surgery, University of Minnesota, Minneapolis, MN, United StatesDepartment of Surgery, University of Minnesota, Minneapolis, MN, United StatesDepartment of Surgery, University of Minnesota, Minneapolis, MN, United StatesDepartment of Surgery, University of Minnesota, Minneapolis, MN, United StatesDepartment of Surgery, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Surgery, University of Minnesota, Minneapolis, MN, United StatesDepartment of Surgery, Stanford University, Palo Alto, CA, United StatesDepartment of Surgery, University of Minnesota, Minneapolis, MN, United StatesDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, United StatesDepartment of Surgery, University of Minnesota, Minneapolis, MN, United StatesThe instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.https://www.frontierspartnerships.org/articles/10.3389/ti.2024.12320/fullislet transplantationdiabetesbeta cell deathanti-inflammatoryTPIAT |
| spellingShingle | Tasneem R. Abdel-Karim James S. Hodges Kevan C. Herold Timothy L. Pruett Karthik V. Ramanathan Bernhard J. Hering Ty B. Dunn Ty B. Dunn Varvara A. Kirchner Varvara A. Kirchner Gregory J. Beilman Melena D. Bellin Melena D. Bellin Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients Transplant International islet transplantation diabetes beta cell death anti-inflammatory TPIAT |
| title | Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients |
| title_full | Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients |
| title_fullStr | Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients |
| title_full_unstemmed | Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients |
| title_short | Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients |
| title_sort | peri transplant inflammation and long term diabetes outcomes were not impacted by either etanercept or alpha 1 antitrypsin treatment in islet autotransplant recipients |
| topic | islet transplantation diabetes beta cell death anti-inflammatory TPIAT |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2024.12320/full |
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