Introduction and Objective: Despite substantial metabolic benefit, islet transplantation (ITx) shows variable graft durability, with ~30% of recipients not sustaining function over time. We used mixed effects regression within a causal directed acyclic graph (DAG) framework to describe baseline determinants of 1 year graft function.Methods: We evaluated data from 415 ITx recipients from the Collaborative Islet Transplant Registry. A DAG represented relationships between baseline variables, initial ITx decisions and 1 year graft function. A total of 237 baseline variables were grouped into categories: immunosuppressant regimen (IR), era, immune status (IS), center, metabolic status (MS) and donor characteristics (DON). Mixed-effects models estimated each baseline association with 1 year graft function, defined as C-peptide normalized to fasting glucose, adjusted for cumulative islet equivalents (IEQs). Variables were ranked by effect size and summarized per category among those p< 0.05.Results: Categories most strongly associated with 1 year graft function were ERA (mean rank=2, range 2-2]), CENTER (13.5, 6-21), IR (14.8, 1-28), IS (21.7, 3-46), DON (45.5, 8-95), and MET (56.6, 7-103). IEQs rank was low (216). The DAG (Fig) specifies baseline effects on 1 year graft function.Conclusion: This DAG-based framework provides a foundation for future machine learning analysis, identifying key baseline determinants of ITx outcome, including era, centre, IR and IS.
A.L. Carr: None. N. Mehta: None. L. Wilson: Research Support; Current; Eli Lilly and Company, Rezolute Bio, Dexcom, Inc. S. Forbes: None. R. Dodier: None. C. Mosquera-Lopez: Employee; Current; Insulet Corporation. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. P.G. Jacobs: Research Support; Current; Dexcom, Inc., Eli Lilly and Company. Advisory Panel; Current; Sequel Medtech. Consultant; Current; Roche Diabetes Care. Research Support; Current; SFC Fluidics. Consultant; Current; 4YouAndMe.
Breakthrough T1D 3-SRA-2025-1715-S-B
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