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- Title
Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients.
- Authors
Abdel-Karim, Tasneem R.; Hodges, James S.; Herold, Kevan C.; Pruett, Timothy L.; Ramanathan, Karthik V.; Hering, Bernhard J.; Dunn, Ty B.; Kirchner, Varvara A.; Beilman, Gregory J.; Bellin, Melena D.
- 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 3months post-TPIAT. Here, we report 2-year diabetes outcomes and perioperative 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 glucosepotentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFa 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.
- Subjects
ETANERCEPT; GLUCOSE tolerance tests
- Publication
Transplant International, 2024, Vol 37, p1
- ISSN
0934-0874
- Publication type
Article
- DOI
10.3389/ti.2024.12320