Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, 3000, Leuven, Belgium.
Crit Care. 2021 Oct 25;25(1):373. doi: 10.1186/s13054-021-03772-6.
Recent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis.
This is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test.
In critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1-3 (P < 0.0001) via infusing insulin at a higher dose (P < 0.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1-3 and significantly lower than the ICU admission values for both groups (P < 0.0001).
Tight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.
最近的证据表明，在重症疾病发作后早期接受低宏量营养素摄入可能会增加酮体的可用性，从而产生潜在的保护作用。胰岛素控制血糖对循环酮体的影响尚不清楚。虽然降低血糖可能会激活酮生成，但高胰岛素浓度可能会产生相反的效果。我们假设，先前报道的在接受早期肠外营养的重症患者中严格血糖控制的保护作用可能部分是通过酮生成的激活介导的。
这是对重症监护病房中严格血糖控制与宽松血糖控制的 3 项随机对照试验的二次分析，包括 700 名重症儿童和 2748 名重症成人。所有患者均接受早期肠外营养作为当代标准治疗的一部分。在研究循环酮体在改善预后中的潜在中介作用之前，我们进行了时间过程分析，以调查严格血糖控制是否会显著影响酮生成，并确定是否存在最大影响的一天。我们从重症监护病房入院开始至第 3 天，在 100 名重症儿童和 100 名重症成人的 2 个匹配亚组中定量检测血浆/血清 3-羟基丁酸浓度。通过 Kruskal-Wallis 检验比较组间的单变量差异。通过 Wilcoxon 符号秩检验比较研究日之间 3-羟基丁酸浓度的差异。
在接受早期肠外营养的重症儿童和成人中，与宽松血糖控制相比，严格血糖控制在第 1-3 天降低了平均早晨血糖（P < 0.0001），方法是输注更高剂量的胰岛素（P < 0.0001）。整个研究期间，两组的热量摄入没有差异。在儿童和成人中，严格血糖控制均未影响 3-羟基丁酸浓度，两组在重症监护病房第 1-3 天均受到抑制，且均明显低于两组的重症监护病房入院值（P < 0.0001）。
在早期肠外营养的背景下，与宽松血糖控制相比，严格血糖控制并未影响重症患者的 3-羟基丁酸浓度。因此，在这种情况下严格血糖控制的保护作用不能归因于酮体可用性的增加。
