Incremental Prognostic Value of Glucose Variability and the Lactate-to-Albumin Ratio Beyond APACHE II After a 48-Hour Landmark in Critically Ill Adults: A Retrospective Cohort Study

Abstract

Background/Objectives: Glucose variability (GV) and the lactate-to-albumin ratio (LAR) have been associated with adverse outcomes in critically ill patients, but their incremental prognostic contribution beyond established severity assessment remains uncertain. This study evaluated the associations of GV and LAR with subsequent mortality and their incremental value beyond APACHE II in a conditional 48 h landmark cohort. Methods: This single-center retrospective cohort study included 384 critically ill adults who were alive and remained in the ICU through 48 h and had sufficient glucose, lactate, and albumin measurements. GV was quantified using the coefficient of variation (CV) from six glucose measurements closest to 0, 8, 16, 24, 32, and 48 h. The primary outcome was all-cause mortality during the 7 days following the 48 h landmark. Firth penalized logistic regression was used for prognostic modeling. Incremental performance was assessed sequentially for APACHE II, APACHE II + LAR, and APACHE II + LAR + GV using discrimination, calibration, Brier score, bootstrap internal validation, and decision-curve analysis. Sensitivity analyses adjusted for mean glycemia and restricted predictor information to the first 24 h. Results: Eighty-eight patients (22.9%) died during the 7-day post-landmark period. APACHE II (OR: 1.19 per point, 95% CI: 1.12–1.27; p < 0.001), LAR (OR: 1.97 per unit, 95% CI: 1.48–2.69; p < 0.001), and GV (OR: 1.07 per 1-percentage-point increase in CV, 95% CI: 1.02–1.11; p = 0.002) were independently associated with mortality. The AUC increased from 0.804 for APACHE II alone to 0.844 after addition of LAR and to 0.857 after further addition of GV. The additional AUC increase attributable to GV after LAR was modest (ΔAUC = 0.013, 95% CI: −0.004 to 0.030; p = 0.145), although model fit and Brier performance improved. The optimism-corrected C-index of the integrated model was 0.851. GV remained independently associated with mortality after adjustment for mean glucose (OR: 1.06, 95% CI: 1.02–1.11; p = 0.002) and in the temporally matched 24 h analysis (OR: 1.05, 95% CI: 1.01–1.09; p = 0.008). Conclusions: Among critically ill adults who survived to a 48 h landmark, LAR and GV provided prognostic information beyond APACHE II. Most of the incremental improvement in discrimination was attributable to LAR, whereas GV provided a smaller additional contribution that remained consistent across sensitivity analyses. These findings support further evaluation of LAR and GV as complementary prognostic markers, but external validation is required before clinical implementation.