Deutz Nicolaas E P, Singer Pierre, Wierzchowska-McNew Raven A, Viana Marina V, Ben-David Itai A, Pantet Olivier, Thaden John J, Ten Have Gabriella A M, Engelen Mariëlle P K J, Berger Mette M
Center for Translational Research in Aging & Longevity, Texas A&M University, United States of America.
Dept of General Intensive Care and Institute for Nutrition Research, Rabin Medical Center, Beilinson Hospital, Sackler School of Medicine, Tel Aviv University, Israel.
Metabolism. 2023 May;142:155400. doi: 10.1016/j.metabol.2023.155400. Epub 2023 Jan 27.
The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females.
In 51 critically ill ICU patients (26 males, 15 females) and 49 healthy controls (36 males and 27 females), we assessed their general and disease characteristics and collected arterial(ized) blood in the postabsorptive state after pulse administration of 8 ml of a solution containing 18 stable AA tracers. In contrast to the original study, we now fitted the decay curves and calculated non-compartmental whole body amino acid production (WBP) and compartmental measurements of metabolism, including intracellular amino acid production. We measured amino acid enrichments and concentrations by LC-MS/MS and derived statistics using AN(C)OVA.
Critically ill males and females showed an increase in the WBP of many amino acids, including those related to protein breakdown, but females showed greater elevations, or in the event of a reduction, attenuated reductions. Protein breakdown-independent WBP differences remained between males and females, notably increased glutamine and glutamate WBP. Only severely ill females showed a lower increase in WBP of many amino acids in comparison to moderately ill females, suggesting a suppressed metabolism. Compartmental analysis supported the observations.
The present study shows that females have a different response to critical illness in the production of several amino acids and changes in protein breakdown, observations made possible using our innovative stable tracer pulse approach.
Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).
从健康到危重病的病程受多种因素影响，包括新陈代谢，而男性和女性的新陈代谢存在显著差异。危重病患者全身蛋白质分解显著增加，但尚不清楚是否存在性别差异可解释不同的健康结局。因此，我们对一项研究进行了二次分析，在该研究中我们对危重病男性和女性以及相匹配的健康男性和女性使用了一种新型脉冲同位素方法。
在51例危重病重症监护病房患者（26例男性，15例女性）和49例健康对照者（36例男性和27例女性）中，我们评估了他们的一般情况和疾病特征，并在脉冲注射8毫升含有18种稳定氨基酸示踪剂的溶液后，在吸收后状态下采集动脉化血液。与原研究不同的是，我们现在拟合了衰变曲线，并计算了非房室全身氨基酸生成量（WBP）和新陈代谢的房室测量值，包括细胞内氨基酸生成量。我们通过液相色谱 - 串联质谱法测量氨基酸富集度和浓度，并使用方差分析（AN(C)OVA）得出统计数据。
危重病男性和女性的许多氨基酸WBP均增加，包括与蛋白质分解相关的氨基酸，但女性的升高幅度更大，或者在减少的情况下，衰减幅度更小。男性和女性之间仍存在与蛋白质分解无关的WBP差异，尤其是谷氨酰胺和谷氨酸WBP显著增加。与中度患病女性相比，只有重度患病女性的许多氨基酸WBP升高幅度较低，表明新陈代谢受到抑制。房室分析支持了这些观察结果。
本研究表明，女性在几种氨基酸生成和蛋白质分解变化方面对危重病有不同反应，这是使用我们创新的稳定示踪脉冲方法得以观察到的。
数据来自研究NCT02770092（网址：https://clinicaltrials.gov/ct2/show/NCT02770092）和NCT03628365（网址：https://clinicaltrials.gov/ct2/show/NCT03628365）的基线测量。
