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Critically ill patients have profound dysregulation of homeostasis and metabolism. It is not clear if the metabolic response to critical illness differs in women compared to men. Such sex-specific differences in illness response would have consequences for personalized medicine. Our aim was to determine the sex-specific metabolomic response to early critical illness. We performed a post-hoc metabolomics study of the VITdAL-ICU trial where subjects received high dose vitamin D<jats:sub>3<\/jats:sub>or placebo. Using mixed-effects modeling, we studied sex-specific changes in metabolites over time adjusted for age, Simplified Acute Physiology Score II, admission diagnosis, day 0 25-hydroxyvitamin D level, and 25-hydroxyvitamin D response to intervention. In women, multiple members of the sphingomyelin and lysophospholipid metabolite classes had significantly positive Bonferroni corrected associations over time compared to men. Further, multiple representatives of the acylcarnitine, androgenic steroid, bile acid, nucleotide and amino acid metabolite classes had significantly negative Bonferroni corrected associations over time compared to men. Gaussian graphical model analyses revealed sex-specific functional modules. Our findings show that robust and coordinated sex-specific metabolite differences exist early in critical illness.<\/jats:p>","DOI":"10.1038\/s41598-021-83602-5","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T16:46:37Z","timestamp":1613753197000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Metabolomic differences between critically Ill women and men"],"prefix":"10.1038","volume":"11","author":[{"given":"Sowmya","family":"Chary","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Amrein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Lasky-Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Dobnig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth B.","family":"Christopher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"83602_CR1","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1097\/ACM.0000000000002027","volume":"93","author":"SE Geller","year":"2018","unstructured":"Geller, S. 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During her Masters, Dr. Chary was employed at Takeda Pharmaceutical Company and is currently employed by Biogen, Inc. Dr. Chary reports receiving salary and stock options from Takeda and from Biogen. Neither Takeda nor Biogen had any involvement in the VITdAL-ICU trial, the identification of metabolites, the post hoc study design, analysis of metabolomics, interpretation of the data, access to the data or writing of the manuscript. Dr. Lasky-Su served as a consultant and received personal fees from Metabolon, Inc., outside the submitted work. Dr. Amrein reports receiving lecture fees from Fresenius Kabi. Dr. Dobnig reports receiving lecture fees from Fresenius Kabi. Dr. Christopher reports no financial or other relationships that might lead to a conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3951"}}