361-OR: BETA-2 Score Is Highly Predictive of Graft Function after Islet Transplant: Analysis of Clinical Islet Transplant Consortium Trials

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. Supplement_1
• Main Authors: SENIOR, PETER A., RICKELS, MICHAEL R., EGGERMAN, THOMAS, BAYMAN, LEVENT, QIDWAI, JULIE, ALEJANDRO, RODOLFO, MARKMANN, JAMES F., HUNSICKER, LAWRENCE G.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2020
• Subjects: Clinical trials; Consortia; Diabetes mellitus (insulin dependent); Graft rejection; Grafts; Hypoglycemia; Immunosuppression; Pancreatic islet transplantation
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db20-361-OR

The safety and efficacy of islet transplant for type 1 diabetes complicated by severe hypoglycemia was tested in a series of trials by the Clinical Islet Transplant (CIT) consortium. We sought to validate BETA-2 score and its utility to track change in graft function over time. 128 subjects (age 48.2 ± 10.9 years, 61.3% female) participated in 7 trials testing different approaches to immunosuppression, with 58 subjects enrolled in a follow-up observational study for up to 8 years. All subjects received 1-3 islet infusions of >4000 IE/kg at least 75 days apart. BETA-2 was calculated at 2.5, 6, 9, 12 months and then annually. Mean follow up was 45.0 months. Graft failure was defined as stimulated C-peptide < 0.3 ng/ml. The effect of time dependent BETA-2 on hazard of subsequent graft loss was estimated by joint analysis. In 120/128 subjects with graft function at day 75, CIT led to a rapid increase in BETA-2 to 24.3 ± 16.4 and remained stable for up to 8 years. 21 subjects who lost graft function after day 75 had lower BETA-2 than subjects who maintained graft function (D75: 14.5 ± 10.0 vs. 21.8 ± 11.1, p = 0.006). Joint analysis showed time dependent BETA-2 was highly predictive of graft loss (a 1 point drop in BETA-2 increased hazard of subsequent graft loss by 17% (eta = -0.19 ± 0.05, p = 0.0001). BETA-2 is a simple, yet powerful tool to describe and predict clinically important changes in graft function.