Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Division of Nutrition, Harvard Medical School, Boston, MA, USA; Programs in Metabolism and Medical & Population Genetics, The Broad Institute of M.I.T and Harvard, Cambridge, MA, USA.
Programs in Metabolism and Medical & Population Genetics, The Broad Institute of M.I.T and Harvard, Cambridge, MA, USA; Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Clin Nutr ESPEN. 2024 Aug;62:28-32. doi: 10.1016/j.clnesp.2024.04.025. Epub 2024 May 13.
Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment. This study aimed to define the metabolic response when HPN is cycled during the daytime compared to overnight.
This secondary analysis leveraged samples from a clinical trial in adults with short bowel syndrome consuming HPN (ClinicalTrials.gov: NCT04743960). Enrolled patients received 1 week of HPN overnight followed by 1 week of HPN during the daytime. Fasting blood samples were collected following each study period and global metabolic profiles were examined from plasma samples. Differential metabolite abundance was determined from normalized and scaled data using adjusted Linear Models for MicroArray Data models followed by pathway enrichment analysis.
Nine patients (mean age, 52.6 years; 78% female; mean BMI 20.7 kg/m) provided samples. Among 622 identified metabolites, changes were observed in 36 metabolites at P < 0.05 with higher abundance of fatty acids, long-chain and polyunsaturated fatty acids (Dihomo-gamma-linolenic acid, arachidonate (20:4n6), docosahexaenoate (DHA; 22:6n3)) and glycerolipids with daytime infusions. Enrichment analysis identified changes in pathways related to the biosynthesis of unsaturated fatty acids, d-arginine, and d-ornithine metabolism, and linoleic acid metabolism (P<0.05).
Daytime infusions of HPN may result in changes in circulating lipids and amino acid composing metabolic pathways previously implicated in circadian rhythms. As this is the first untargeted metabolomics study of HPN, larger studies are needed.
家庭肠外营养（HPN）通常在夜间循环进行，由于昼夜节律失调，预计会导致葡萄糖不耐受和睡眠中断。本研究旨在定义与夜间相比，HPN 在白天循环时的代谢反应。
本二次分析利用了短肠综合征成人接受 HPN 治疗的临床试验中的样本（ClinicalTrials.gov：NCT04743960）。入组患者接受了 1 周的夜间 HPN 治疗，随后进行了 1 周的日间 HPN 治疗。在每个研究期后采集空腹血样，并从血浆样本中检查全代谢谱。使用调整后的微阵列数据模型的线性模型对标准化和缩放数据进行差异代谢物丰度测定，然后进行途径富集分析。
9 名患者（平均年龄 52.6 岁；78%为女性；平均 BMI 为 20.7kg/m）提供了样本。在 622 种鉴定的代谢物中，有 36 种代谢物的变化具有统计学意义（P<0.05），日间输注时脂肪酸、长链和多不饱和脂肪酸（二同型-γ-亚麻酸、花生四烯酸（20:4n6）、二十二碳六烯酸（DHA；22:6n3））和甘油脂质的丰度更高。富集分析确定了与不饱和脂肪酸、d-精氨酸和 d-鸟氨酸代谢以及亚油酸代谢相关的途径发生了变化（P<0.05）。
日间输注 HPN 可能导致循环脂质和组成代谢途径的氨基酸发生变化，这些变化先前与昼夜节律有关。由于这是 HPN 的第一项非靶向代谢组学研究，因此需要更大的研究。
