ArticleResearch square2026
Global carbohydrate metabolism is increased and beta hydroxybutyrate decreased in sepsis vulnerable children compared to sepsis tolerant children; a cohort study.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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20 authors.
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Abstract
Background: Sepsis investigators propose tolerance is conferred when the dormancy response increases beta hydroxybutyrate to protect organs; whereas, vulnerability occurs when a 'metabolic switch' to aerobic glycolysis decreases beta hydroxybutyrate promoting persistent immune cell activation without organ protection. We previously identified tolerant (PedSep A 2% mortality), susceptible (PedSep B 12% mortality and PedSep C 10% mortality) and vulnerable (PedSep D 34% mortality) phenotypes in the PHENOtyping pediatric sepsis induced Multiple organ failure Study (PHENOMS). We hypothesized that carbohydrate metabolism was increased and beta hydroxybutyrate decreased in PedSep D compared to PedSep A in this study. Methods: Metabolomics were assayed in biobanked plasma samples previously collected at 24-48 hours of sepsis in 375 children ages 44 weeks post gestation to 17 years, using the Metabolon Discovery Panel. Welch's t-tests identified differences between PedSep B, C, and D with A. Results: Compared to PedSep A (n =130) PedSep B had similar carbohydrate metabolism and beta hydroxybutyrate but dysregulated branch chain amino acid metabolism (n = 92; p < 0.05); PedSep C had similar carbohydrate metabolism but decreased beta hydroxybutyrate (n = 100; p< 0.05); and, PedSep D had increased carbohydrate metabolism with decreased beta hydroxybutyrate (n = 53; p < 0.05). Causal inference analysis found direct associations of increased glycolysis with decreased beta hydroxybutyrate, and death. Conclusions: Only PedSep D had increased carbohydrate metabolism with decreased beta hydroxybutyrate providing rationale for designing clinical trials of low carbohydrate ketogenic nutrition to decrease glycolysis, restore dormancy, and improve outcome in these high-risk children.
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