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Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients

Authors :
Tasneem R. Abdel-Karim
James S. Hodges
Kevan C. Herold
Timothy L. Pruett
Karthik V. Ramanathan
Bernhard J. Hering
Ty B. Dunn
Varvara A. Kirchner
Gregory J. Beilman
Melena D. Bellin
Source :
Transplant International, Vol 37 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

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.

Details

Language :
English
ISSN :
14322277
Volume :
37
Database :
Directory of Open Access Journals
Journal :
Transplant International
Publication Type :
Academic Journal
Accession number :
edsdoj.59a5c9a352c64d349d9c0a3738f741f5
Document Type :
article
Full Text :
https://doi.org/10.3389/ti.2024.12320