The following is a summary of “Association between primary graft function and 5-year outcomes of islet allogeneic transplantation in type 1 diabetes: a retrospective, multicentre, observational cohort study in 1210 patients from the Collaborative Islet Transplant Registry,” published in the June 2023 issue of Diabetes & Endocrinology by Chetboun et al.

Allogeneic islet transplantation is a validated treatment for type 1 diabetes; however, transplanted islet graft function declines over time for unknown reasons. Researchers investigated the relationship between primary graft function (PGF) and 5-year islet transplantation outcomes. In this retrospective, multicenter, observational cohort study, researchers enrolled all patients from the Collaborative Islet Transplant Registry who received islet transplantation alone (ITA recipients) or islet-after-kidney transplantation (IAK recipients) between January 19, 1999, and July 17, 2020, and had a calculable PGF (exposure of interest) measured 28 days after the last islet infusion using a validated composite index of islet graft function (BETA-2 score). 

The primary outcome was cumulative incidence of unsuccessful islet transplantation, which was defined as an HbA_1c of 70% (53 mmol/mol) or higher, or severe hypoglycemia (requiring third-party intervention to correct), or a fasting C-peptide concentration of less than 0.2 ng/mL. The secondary outcomes were graft exhaustion (fasting C-peptide 0.3 ng/mL), inadequate glucose control (HbA_1ct  7% [53 mmol/mol] or severe hypoglycemia), and the need for exogenous insulin therapy (14 consecutive days). The associations between PGF and islet transplantation outcomes were investigated using a competing risk analysis adjusted for all covariates suspected or known to affect transplantation outcomes. Using the bootstraps resampling technique, a PGF-based predictive model was created and internally validated.

In 39 centers around the world, researchers enrolled 1,210 patients with a calculable PGF (of those without missing data, the mean age was 47 years [SD 10], 712 [59.5%] were female, and 865 [97.9%] were White), who received a median of 10.8 thousand islet-equivalents per kilogram of body weight (interquartile range [IQR]: 7.4–13.0). 986 (82.4%) were beneficiaries of the ITA, while 211 (17.6%) were recipients of the IAK. About 452 (37.4%) of 1,210 patients received a single islet infusion, while 758 (62.6%) received multiple infusions. Mean PGF was 14.3 (SD: 8.8). The 5-year cumulative incidence of failed islet transplantation was 70.7% (95% CI 67.2–73.9) and was inversely and linearly related to PGF, with an adjusted sub-hazard ratio (sHR) of 0.77 (95% CI 0.72–0.82) per 5-unit increase in BETA-2 score (P<00001). Secondary endpoints were similarly related to PGF. Model-adjusted median C-statistic values of PGF for predicting 5-year cumulative incidences of failed islet transplantation, graft exhaustion, inadequate glucose control, and exogenous insulin therapy were 0.70 (range 0.69–0.71), 0.76 (0.74–0.77), 0.65 (0.64–0.66), and 0.72 (0.71–0.73), respectively.

Source: sciencedirect.com/science/article/abs/pii/S2213858723000827