Metabolic phenotyping and a prognostic score for simultaneous pancreas-kidney transplantation in type 2 diabetes mellitus with kidney failure: a single-center exploratory study based on the Chinese population

Selection criteria for simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) and kidney failure are extrapolated from type 1 diabetes and do not capture the metabolic heterogeneity of T2DM, particularly in East Asian populations. We developed and internally validated an exploratory prognostic score based on pretransplant metabolic phenotyping. In this single-center cohort study (2015–2025), 218 patients with T2DM and kidney failure received SPK ( n = 128) or kidney transplantation alone (KTA; n = 90). Phenotyping comprised dynamic C-peptide, insulin resistance (HOMA-IR) and visceral fat area (VFA). LASSO Cox regression was used to derive the Chinese SPK-T2DM Prognostic Score (CSTPS), validated internally by nested cross-validation and bootstrap correction. The primary endpoint comprised all-cause death, death-censored kidney graft failure or major adverse cardiovascular events (MACE), all applicable to both groups; pancreas graft failure was analyzed separately. All SPK–KTA comparisons were associative. Over a median follow-up of 4.8 years, the primary endpoint occurred in 22 of 128 SPK recipients (17.2%) and 57 of 90 KTA recipients (63.3%) (unadjusted hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.15–0.41, P < 0.001). Glycemic control was also better after SPK (HbA1c < 7.0%: 78.9% versus 31.1%, P < 0.001). Five variables were retained: C-peptide120 ≥ 1.5 ng/mL, HOMA-IR < 4.5, VFA < 100 cm², diabetes duration < 15 years and age < 55 years. Discrimination was modest (C-statistic 0.537, 95% CI 0.396–0.683) and the score was not significantly associated with the SPK-specific endpoint (HR 0.92 per 10-point increase, P = 0.34). Crude event rates across strata were 8.3%, 28.9% and 44.4% (log-rank P = 0.046); the interaction test suggested heterogeneity of the treatment association ( P = 0.032). Metabolic phenotyping identified five variables associated with post-SPK outcomes, but the resulting score achieved only modest stratification and no validated discrimination; few events, outcome-driven thresholds and the absence of external validation preclude its use for prediction or as an indication tool. Independent external validation is required. ClinicalTrials.gov, NCT05497232. Registered 11 August 2022. Retrospectively registered. NCT05497232 (ClinicalTrials.gov).