{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:40:49Z","timestamp":1787020849757,"version":"build-2736575974"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007601","name":"horizon 2020","doi-asserted-by":"publisher","award":["AdvG 2017-785809"],"award-info":[{"award-number":["AdvG 2017-785809"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011878","name":"vlaamse regering","doi-asserted-by":"publisher","award":["METH14\/06"],"award-info":[{"award-number":["METH14\/06"]}],"id":[{"id":"10.13039\/501100011878","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011878","name":"vlaamse regering","doi-asserted-by":"publisher","award":["METH14\/06"],"award-info":[{"award-number":["METH14\/06"]}],"id":[{"id":"10.13039\/501100011878","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003132","name":"agentschap voor innovatie door wetenschap en technologie","doi-asserted-by":"publisher","award":["IWT\/070695"],"award-info":[{"award-number":["IWT\/070695"]}],"id":[{"id":"10.13039\/501100003132","id-type":"DOI","asserted-by":"publisher"}]},{"name":"research foundation flanders, belgium","award":["G.0C78.17N"],"award-info":[{"award-number":["G.0C78.17N"]}]},{"name":"research foundation flanders, belgium","award":["postdoctoral research fellowship"],"award-info":[{"award-number":["postdoctoral research fellowship"]}]},{"name":"research foundation flanders, belgium","award":["G.0C78.17N"],"award-info":[{"award-number":["G.0C78.17N"]}]},{"name":"university hospitals leuven","award":["postdoctoral research fellowship"],"award-info":[{"award-number":["postdoctoral research fellowship"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Crit Care"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma\/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1\u20133 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001) via infusing insulin at a higher dose (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1\u20133 and significantly lower than the ICU admission values for both groups (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13054-021-03772-6","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T10:03:56Z","timestamp":1635156236000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-6393","authenticated-orcid":false,"given":"Jan","family":"Gunst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1252-4982","authenticated-orcid":false,"given":"Astrid","family":"De Bruyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7087-0795","authenticated-orcid":false,"given":"Michael P.","family":"Casaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Vander Perre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-6809","authenticated-orcid":false,"given":"Lies","family":"Langouche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5320-1362","authenticated-orcid":false,"given":"Greet","family":"Van den Berghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"issue":"4","key":"3772_CR1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1097\/MCC.0000000000000841","volume":"27","author":"J Gunst","year":"2021","unstructured":"Gunst J, Casaer MP, Langouche L, Van den Berghe G. Role of ketones, ketogenic diets and intermittent fasting in ICU. Curr Opin Crit Care. 2021;27(4):385\u20139.","journal-title":"Curr Opin Crit Care"},{"issue":"1","key":"3772_CR2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.tem.2013.09.002","volume":"25","author":"JC Newman","year":"2014","unstructured":"Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014;25(1):42\u201352.","journal-title":"Trends Endocrinol Metab"},{"issue":"1","key":"3772_CR3","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/s13054-019-2506-6","volume":"23","author":"C Goossens","year":"2019","unstructured":"Goossens C, Weckx R, Derde S, Dufour T, Vander Perre S, Pauwels L, et al. Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones. 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Ref 12\/2020.04."}],"container-title":["Critical Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13054-021-03772-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13054-021-03772-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13054-021-03772-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T10:04:11Z","timestamp":1635156251000},"score":1,"resource":{"primary":{"URL":"https:\/\/ccforum.biomedcentral.com\/articles\/10.1186\/s13054-021-03772-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,25]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3772"],"URL":"https:\/\/doi.org\/10.1186\/s13054-021-03772-6","relation":{},"ISSN":["1364-8535"],"issn-type":[{"value":"1364-8535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,25]]},"assertion":[{"value":"7 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This is a secondary analysis of 3 monocenter (Leuven, BE) randomized controlled trials (ML 2586 and ClinicalTrials.gov NCT00214916, <i>n<\/i>\u2009=\u2009700; ML1820 and ClinicalTrials.gov NCT00115479, <i>n<\/i>\u2009=\u20091200; ML1094, <i>n<\/i>\u2009=\u20091548). The institutional review board approved the study protocols. Written informed consent was obtained from the patients or next of kin, or (for children) from the parents or legal guardian.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"We declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"373"}}