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 feeding 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 feeding 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, 208,153 glucose measurements collected during enteral feeding were available from 6,944 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 9.4 [9.4-9.5; estimated marginal means, 95% CI] mmol/L at 10:00 in the morning and a trough of 8.5 [8.4-8.5] 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 feeding. This 24-hour pattern persists after adjustment for potential sources of bias, suggesting it may be the result of endogenous biological rhythmicity.

The authors have declared no competing interest.

This work was supported by a VENI grant (2020-09150161910128) from the Netherlands Organization for Health Research and Development (ZonMw) and an institutional project grant from the LUMC.

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The Institutional Review Board at the Beth Israel Deaconess Medical Center granted a waiver of informed consent for the data collected in the MIMIC-IV database (that was used in this study).

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