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.
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.
EBioMedicine. 2024 Jun;104:105169. doi: 10.1016/j.ebiom.2024.105169. Epub 2024 May 30.
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.
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.
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.
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.
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).
昼夜节律计时系统协调着包括葡萄糖代谢和胰岛素敏感性在内的生理功能的日常节律。本研究旨在控制潜在偏倚来源的情况下，描述接受持续肠内营养的重症患者的血糖水平 24 小时变化。
从 Medical Information Mart for Intensive Care (MIMIC)-IV 数据库中提取至少在重症监护病房（ICU）中停留 4 天并接受肠内营养的成年患者的时间标记临床数据。采用线性混合效应和 XGBoost 模型来确定时间对血糖值的影响。
共从 6929 例 ICU 患者（3948 名男性和 2981 名女性）中获得了 207647 次肠内营养期间的血糖测量值。使用线性混合效应模型，时间对血糖水平有显著影响（p<0.001），早上 10 点时血糖峰值为 9.6[9.5-9.6；估计边缘均值，95%CI]mmol/L，晚上 2 点时血糖谷值为 8.6[8.5-8.6]mmol/L。XGBoost 回归模型也发现了时间对血糖水平的类似影响。
这些结果表明，即使在持续接受肠内营养的情况下，ICU 患者的血糖水平也存在明显的 24 小时变化。这种 24 小时模式在调整潜在偏倚来源后仍然存在，这表明它可能是内源性生物节律性的结果。
这项工作得到了荷兰健康研究与发展组织（ZonMw）的 VENI 拨款、机构项目拨款和荷兰研究委员会（NWO）的资助。
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