Faculty Collaboration Database

Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients. Transpl Int 2024;37:12320

Date

02/15/2024

Pubmed ID

38357216

Pubmed Central ID

PMC10864605

DOI

10.3389/ti.2024.12320

Scopus ID

2-s2.0-85184719005 (requires institutional sign-in at Scopus site)

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.

Author List

Abdel-Karim TR, Hodges JS, Herold KC, Pruett TL, Ramanathan KV, Hering BJ, Dunn TB, Kirchner VA, Beilman GJ, Bellin MD

Author

Ty Blink Dunn MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Autografts
Cytokines
DNA
Diabetes Mellitus
Etanercept
Humans
Inflammation
Insulin
Islets of Langerhans Transplantation
Pancreatectomy
Transplantation, Autologous
Treatment Outcome