Daily variation in blood glucose levels during continuous enteral nutrition in patients on the intensive care unit: a retrospective observational study

EBioMedicine. 2024 Jun:104:105169. doi: 10.1016/j.ebiom.2024.105169. Epub 2024 May 30.


Background: The circadian timing system coordinates daily cycles in physiological functions, including glucose metabolism and insulin sensitivity. Here, the aim was to characterise the 24-h variation in glucose levels in critically ill patients during continuous enteral nutrition after controlling for potential sources of bias.

Methods: Time-stamped clinical data from adult patients who stayed in the Intensive Care Unit (ICU) for at least 4 days and received enteral nutrition were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Linear mixed-effects and XGBoost modelling were used to determine the effect of time of day on blood glucose values.

Findings: In total, 207,647 glucose measurements collected during enteral nutrition were available from 6,929 ICU patients (3,948 males and 2,981 females). Using linear mixed-effects modelling, time of day had a significant effect on blood glucose levels (p < 0.001), with a peak of 9.6 [9.5-9.6; estimated marginal means, 95% CI] mmol/L at 10:00 in the morning and a trough of 8.6 [8.5-8.6] mmol/L at 02:00 at night. A similar impact of time of day on glucose levels was found with the XGBoost regression model.

Interpretation: These results revealed marked 24-h variation in glucose levels in ICU patients even during continuous enteral nutrition. This 24-h pattern persists after adjustment for potential sources of bias, suggesting it may be the result of endogenous biological rhythmicity.

Funding: This work was supported by a VENI grant from the Netherlands Organisation for Health Research and Development (ZonMw), an institutional project grant, and by the Dutch Research Council (NWO).

Keywords: Circadian rhythm; Critical illness; Daily variation; Electronic health records; Enteral nutrition; Glucose; Intensive care.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Blood Glucose* / metabolism
  • Circadian Rhythm
  • Critical Illness
  • Enteral Nutrition* / methods
  • Female
  • Humans
  • Intensive Care Units*
  • Male
  • Middle Aged
  • Retrospective Studies


  • Blood Glucose