TY - JOUR
T1 - Metabolites Associated with Malnutrition in the Intensive Care Unit Are Also Associated with 28-Day Mortality
AU - Mogensen, Kris M.
AU - Lasky-Su, Jessica
AU - Rogers, Angela J.
AU - Baron, Rebecca M.
AU - Fredenburgh, Laura E.
AU - Rawn, James
AU - Robinson, Malcolm K.
AU - Massarro, Anthony
AU - Choi, Augustine M.K.
AU - Christopher, Kenneth B.
N1 - Funding Information:
This work was supported by the ASPEN Rhoads Research Foundation.
Publisher Copyright:
© The American Society for Parenteral and Enteral Nutrition.
PY - 2017/2
Y1 - 2017/2
N2 - Background: We hypothesized that metabolic profiles would differ in critically ill patients with malnutrition relative to those without. Materials and Methods: We performed a prospective cohort study on 85 adult patients with systemic inflammatory response syndrome or sepsis admitted to a 20-bed medical intensive care unit (ICU) in Boston. We generated metabolomic profiles using gas and liquid chromatography and mass spectroscopy. We followed this by logistic regression and partial least squares discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis and network model construction of chemical-protein target interactions to identify groups of metabolites and pathways that were differentiates in patients with and without malnutrition. Results: Of the cohort, 38% were malnourished at admission to the ICU. Metabolomic profiles differed in critically ill patients with malnutrition relative to those without. Ten metabolites were significantly associated with malnutrition (P <.05). A parsimonious model of 5 metabolites effectively differentiated patients with malnutrition (AUC = 0.76), including pyroglutamine and hypoxanthine. Using pathway enrichment analysis, we identified a critical role of glutathione and purine metabolism in predicting nutrition. Nutrition status was associated with 28-day mortality, even after adjustment for known phenotypic variables associated with ICU mortality. Importantly, 7 metabolites associated with nutrition status were also associated with 28-day mortality. Conclusion: Malnutrition is associated with differential metabolic profiles early in critical illness. Common to all of our metabolome analyses, glutathione and purine metabolism, which play principal roles in cellular redox regulation and accelerated tissue adenosine triphosphate degradation, respectively, were significantly altered with malnutrition.
AB - Background: We hypothesized that metabolic profiles would differ in critically ill patients with malnutrition relative to those without. Materials and Methods: We performed a prospective cohort study on 85 adult patients with systemic inflammatory response syndrome or sepsis admitted to a 20-bed medical intensive care unit (ICU) in Boston. We generated metabolomic profiles using gas and liquid chromatography and mass spectroscopy. We followed this by logistic regression and partial least squares discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis and network model construction of chemical-protein target interactions to identify groups of metabolites and pathways that were differentiates in patients with and without malnutrition. Results: Of the cohort, 38% were malnourished at admission to the ICU. Metabolomic profiles differed in critically ill patients with malnutrition relative to those without. Ten metabolites were significantly associated with malnutrition (P <.05). A parsimonious model of 5 metabolites effectively differentiated patients with malnutrition (AUC = 0.76), including pyroglutamine and hypoxanthine. Using pathway enrichment analysis, we identified a critical role of glutathione and purine metabolism in predicting nutrition. Nutrition status was associated with 28-day mortality, even after adjustment for known phenotypic variables associated with ICU mortality. Importantly, 7 metabolites associated with nutrition status were also associated with 28-day mortality. Conclusion: Malnutrition is associated with differential metabolic profiles early in critical illness. Common to all of our metabolome analyses, glutathione and purine metabolism, which play principal roles in cellular redox regulation and accelerated tissue adenosine triphosphate degradation, respectively, were significantly altered with malnutrition.
KW - critical care
KW - intensive care
KW - metabolism
KW - metabolomics
KW - mortality
KW - nutrition status
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U2 - 10.1177/0148607116656164
DO - 10.1177/0148607116656164
M3 - Article
C2 - 27406941
AN - SCOPUS:85011580145
SN - 0148-6071
VL - 41
SP - 188
EP - 197
JO - Journal of Parenteral and Enteral Nutrition
JF - Journal of Parenteral and Enteral Nutrition
IS - 2
ER -