Year: 2017
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Metabolic homeostasis is substantially disrupted in critical illness. Given the pleiotropic effects of vitamin D, we hypothesized that metabolic profiles differ between critically ill patients relative to their vitamin D status. METHODS: We performed a metabolomics study on biorepository samples collected from a single academic medical center on 65 adults with systemic inflammatory response syndrome or sepsis treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to vitamin D status in critical illness, we first generated metabolomic data using gas and liquid chromatography mass spectroscopy. We followed this by partial least squares-discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis to identify groups of metabolites and pathways that were differentiates of vitamin D status. Finally we performed logistic regression to construct a network model of chemical-protein target interactions important in vitamin D status. RESULTS: Metabolomic profiles significantly differed in critically ill patients with 25(OH)D ≤ 15 ng/ml relative to those with levels >15 ng/ml. In particular, increased 1,5-anhydroglucitol, tryptophan betaine, and 3-hydroxyoctanoate as well as decreased 2-arachidonoyl-glycerophosphocholine and N-6-trimethyllysine were strong predictors of 25(OH)D >15 ng/ml. The combination of these five metabolites led to an area under the curve for discrimination for 25(OH)D > 15 ng/ml of 0.82 (95% CI 0.71-0.93). The metabolite pathways related to glutathione metabolism and glutamate metabolism are significantly enriched with regard to vitamin D status. CONCLUSION: Vitamin D status is associated with differential metabolic profiles during critical illness. Glutathione and glutamate pathway metabolism, which play principal roles in redox regulation and immunomodulation, respectively, were significantly altered with vitamin D status.
Source: Critical Care
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: Biology of Vascular, Lung and Blood Diseases, Integrative Metabolomics of Asthma Severity, G2727228598, Role of Cyclooxygenase-2-derived Prostanoids in Polymicrobial Sepsis, Heme Oxygenase-1/Carbon Monoxide in sepsis, Pharmacokinetics and metabolomics of vitamin D supplementation in critical illness, Role of microRNA molecules in therapeutic response to leukotriene modifying agents in asthma, Carbon Monoxide: Novel Opportunities for Therapy, The Inflammasome: A Novel Biomarker in ALI/ARDS, Translational Genetics and Genomics of Airways Diseases, Role of NOS2 in Sepsis-Induced ARDS, G9000167643, Training Program in Molecular and Integrative Physiological Sciences
OpenAlex ID: W2740750635