Daily variation in blood glucose levels during continuous enteral nutrition in patients on the Intensive Care Unit: a retrospective observational study

Background The circadian timing system coordinates daily cycles in physiological functions, including glucose metabolism and insulin sensitivity. Here, the aim was to characterize the 24-hour 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. 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 03:00 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-hour variation in glucose levels in ICU patients even during continuous enteral nutrition. This 24-hour 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 (2020-09150161910128) from the Netherlands Organization for Health Research and Development (ZonMw), an institutional project grant, and by the Dutch Research Council (NWO).