# First-Day Glycemic Exposure and 28-Day Mortality in the ICU: A Multicenter Cohort Study

## TL;DR

High blood sugar levels in the first day of ICU care are linked to higher 28-day mortality, and a new model helps predict risk early.

## Contribution

Introduces GlucoSurvAI, an interpretable model for early ICU mortality risk prediction using first-day glycemic exposure.

## Key findings

- Higher first-day TWAG (≥140 mg/dL) is associated with increased 28-day mortality.
- GlucoSurvAI achieved high accuracy (AUROC 0.967) in predicting mortality risk.
- Vasopressors and corticosteroids on day 1 are linked to higher mortality.

## Abstract

Early glycemic exposure in the ICU is common and clinically modifiable, yet bedside assessment often relies on single glucose values rather than exposure-aware metrics. Interpretable, first-day prediction may support individualized glycemic targets and early intervention.

To examine the association between first-day time-weighted average glucose (TWAG) and 28-day mortality, and to evaluate GlucoSurvAI, an interpretable ensemble model for first-day risk stratification.

Retrospective cohort study using electornic health records from 13 U.S. hospitals. Among 18,868 adult ICU encounters, 8,048 patients from 7 U.S. hospitals met inclusion criteria (≥1 glucose value and hospital length of stay ≥24 hours).

First-day glycemic exposure summarized as TWAG, categorized as <100, 100–139 (reference), 140–179, and ≥180 mg/dL. Prespecified covariates included diabetes/prediabetes, first-day insulin and glucose, corticosteroids, vasopressors, shock, cancer, glucose-monitoring intensity, and clinical site.

Primary outcome: 28-day all-cause mortality. Associations were estimated with multivariable Cox models (adjusted hazard ratios [aHRs], 95% CIs). GlucoSurvAI performance was assessed using Area Under the Receiver Operating Characteristic (AUROC) and Brier score; SHapley Additive exPlanations (SHAP) provided 28-day interpretability.

Of 8,048 patients, most were euglycemic (70–180 mg/dL) on day 1, although hyperglycemic excursions were frequent. Higher TWAG was associated with higher 28-day mortality: 140–179 mg/dL aHR 1.42 (95% CI, 1.25–1.62); ≥180 mg/dL aHR 1.41 (95% CI, 1.17–1.69). TWAG <100 mg/dL showed a nonsignificant trend toward higher survival. GlucoSurvAI achieved AUROC 0.967 (±0.008) with a low Brier score (~0.026). Adjusted SHAP analyses paralleled Cox results, identifying 100–139 mg/dL as the exposure range associated with decreased mortality, with risk increasing ≥140 mg/dL. First-day vasopressors and corticosteroids were also associated with higher mortality; insulin exposure marked higher risk after adjustment.

During the first ICU day, exposure-aware TWAG assessmentidentified a practical upper boundary near 140 mg/dL associated with higher 28-day mortality. An interpretable ensemble integrating TWAG, treatments, and physiology provided accurate first-day risk estimates, supporting risk-informed, individualized glycemic targets and earlier intervention in high-risk ICU patients.