One-Year HbA1c Predicts Long-Term Pancreas Graft Survival Following SPK Transplantation: A US Population Cohort Study

Abstract

Understanding which factors shape long-term pancreas graft outcomes after the critical first year post-transplantation is an ongoing challenge. This study assesses one-year HbA1c as a predictor of subsequent pancreas graft survival. A retrospective cohort study was conducted using the UNOS registry on all simultaneous pancreas-kidney (SPK) transplants between 2017 and 2023. Regression models with multiple imputations for missing data were used to evaluate predictors of long-term function. Non-linear relationships were modelled with restricted cubic splines (RCS). Among 2,917 SPK recipients (median follow-up 44 months, IQR: 25-60), one-year HbA1c was the strongest independent predictor of long-term graft survival. An HbA1c of 6.8% versus 4.4% (95th vs. 5th percentile) was associated with significantly worse graft survival (aHR = 2.48, 95% CI: 1.72-3.58). Simulated trial sample size calculations found that detecting a statistically and clinically significant reduction in one-year HbA1c from 7% to 6.5% would require 65 patients per group, whereas detecting a reduction in one-year graft loss from 12% to 9% would require 1,631 patients per group. HbA1c at 1 year is a robust, continuous marker of long-term graft function and may serve as a feasible, objective surrogate endpoint in future clinical trials, enabling smaller, more efficient study designs to evaluate interventions.

Keywords: glycosylated hemoglobin (HbA1c); graft survival; long-term outcomes; pancreas transplantation; simultaneous pancreas-kidney transplantation.

FIGURE 1

Flowchart of recipients included in the study.

FIGURE 2

(A) Histogram showing the distribution of 1-year HbA1c levels in the study cohort; (B) Kaplan-Meier survival curves illustrating crude univariable long-term graft survival over days post- transplantation (starting from 1 year after transplantation), stratified by HbA1c levels of <5.7% and ≥5.7%.

FIGURE 3

Model terms ranked by significance in predicting long-term pancreas graft survival.

FIGURE 4

Adjusted hazard ratio for pancreas graft survival based on recipient (A) HbA1c (% DCCT) and (B) eGFR (mL/min/1.73 m²) at 1 year. The non-linear relationship is shown with restricted cubic splines analysis. HbA1c was modeled with 4 knots, while eGFR used 3 knots.

FIGURE 5

Sample sizes required to detect the desired minimum clinically important difference across the range of values on the x-axis (A) a change in one-year mean HbA1c from 7% (e.g., a reduction from 7% to 6.5% would require 65 patients per group) and (B) a relative risk reduction in graft loss from 20% at 1 year (e.g., a reduction from 20% to 16% would require 1,444 patients per group).