Daily variation in blood glucose levels during continuous enteral nutrition in patients on the intensive care unit: a retrospective observational studyResearch in context
Floor W. Hiemstra,
Dirk Jan Stenvers,
Andries Kalsbeek,
Evert de Jonge,
David J. van Westerloo,
Laura Kervezee
Affiliations
Floor W. Hiemstra
Department of Intensive Care, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, the Netherlands; Group of Circadian Medicine, Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, the Netherlands
Dirk Jan Stenvers
Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Andries Kalsbeek
Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands; Netherlands Institute for Neuroscience (NIN), Royal Dutch Academy of Arts and Sciences (KNAW), Meibergdreef 47, Amsterdam 1105 BA, the Netherlands; Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands
Evert de Jonge
Department of Intensive Care, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, the Netherlands
David J. van Westerloo
Department of Intensive Care, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, the Netherlands
Laura Kervezee
Group of Circadian Medicine, Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, the Netherlands; Corresponding author. Group of Circadian Medicine, Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, the Netherlands.
Summary: 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).
