Detecting the metabolic transition to personalize nutritional timing: model development and preliminary validation in a large ICU cohort

The metabolic transition from catabolism to anabolism is a key determinant of recovery in critical illness and should guide nutritional therapy. However, no validated clinical marker currently exists to identify this transition, and current clinical practice relies on calendar-based recommendations. We aim to develop and preliminarily validate a physiology-based, trajectory-driven model to detect the metabolic transition window in critically ill patients. We conducted a retrospective cohort study in a tertiary-care general ICU. A daily insulin resistance index (IRI) was computed from glucose and insulin data and corrected for steroid exposure. Transition was defined as a ≥ 30% sustained drop in IRI after its peak, together with ≥ 2 of 8 physiologic recovery criteria (lactate, noradrenaline, vasopressin, adrenaline, inflammatory markers-WBC, %neutrophils, CRP, and albumin). Associations with 90-day mortality and caloric exposure were evaluated using Kaplan–Meier analysis and multivariable landmark Cox models. The cohort included 2,350 patients (age 59.8 ± 16.5 years; SOFA 11.7 ± 3.9; 82% mechanically ventilated). A metabolic transition was identified in 94% of patients, with ~ 60% transitioning by ICU day 3. Transition by day 3 was associated with lower 90-day mortality (HR 0.72, 95% CI 0.65–0.81). Patients who never transitioned had substantially higher mortality. High caloric delivery (≥ 1.0 kcal/kg/h for ≥ 24 h) before transition was independently associated with increased 90-day mortality (OR 1.25, 95% CI 1.01–1.55), with a dose–response pattern. In contrast, high caloric delivery based on calendar timing failed to demonstrate a similar pattern. We developed and validated a physiological model for detecting metabolic transition in critical illness and showed that transition occurs early and strongly predicts survival. Higher caloric delivery before transition is associated with increased mortality, supporting nutrition strategies aligned with physiological recovery rather than fixed calendar days.