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.
P.A. Senior: None. M.R. Rickels: Consultant; Self; Semma Therapeutics, Inc. Research Support; Self; Xeris Pharmaceuticals, Inc. T. Eggerman: None. L. Bayman: None. J. Qidwai: None. R. Alejandro: None. J.F. Markmann: None. L.G. Hunsicker: Advisory Panel; Self; Allergan plc., Bristol-Myers Squibb.