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Here, we assessed endogenous circadian rhythms and wake-dependent changes in plasma metabolites in 13 participants (4 females) studied during 40-hours of wakefulness. Four-hourly plasma samples were analyzed by hydrophilic interaction liquid chromatography (HILIC)-LC-MS for 1,740 metabolite signals. Group-averaged (relative to DLMO) and individual participant metabolite profiles were fitted with a combined cosinor and linear regression model. In group-level analyses, 22% of metabolites were rhythmic and 8% were linear, whereas in individual-level analyses, 14% of profiles were rhythmic and 4% were linear. We observed metabolites that were significant at the group-level but not significant in a single individual, and metabolites that were significant in approximately half of individuals but not group-significant. Of the group-rhythmic and group-linear metabolites, only 7% and 12% were also significantly rhythmic or linear, respectively, in \u226550% of participants. Owing to large inter-individual variation in rhythm timing and the magnitude and direction of linear change, acrophase and slope estimates also differed between group- and individual-level analyses. These preliminary findings have important implications for biomarker development and understanding of sleep and circadian regulation of metabolism.<\/jats:p>","DOI":"10.1038\/s41598-019-40353-8","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T12:06:06Z","timestamp":1552565166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis"],"prefix":"10.1038","volume":"9","author":[{"given":"Leilah K.","family":"Grant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Ftouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunda","family":"Nijagal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"De Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dedreia","family":"Tull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm J.","family":"McConville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantha M. 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Grant<sub>,<\/sub> Suzanne Ftouni, Brunda Nijagal, David P. De Souza, Dedreia Tull, Malcolm J. McConville, Shantha M. W. Rajaratnam, Steven W. Lockley, Clare Anderson, L.K.G. received a top up Scholarship from the Cooperative Research Centre for Alertness Safety and Productivity and was supported by an Australian Government Research Training Program (RTP) Scholarship. S.F. served as a Project Leader for the Cooperative Research Centre for Alertness, Safety and Productivity. B.N., D.P.D. and D.T. report no financial conflicts of interest in relation to this work. M.J.M. is an NHMRC Principle Research Fellow. S.M.W.R. reports that he has served as a consultant through his institution to Vanda Pharmaceuticals, Philips Respironics, EdanSafe, The Australian Workers\u2019 Union, National Transport Commission, Transport Accident Commission, New South Wales Department of Education and Communities, and has through his institution received research grants and\/or unrestricted educational grants from Vanda Pharmaceuticals, Shell, Teva Pharmaceuticals, Rio Tinto, Seeing Machines, Takeda Pharmaceuticals North America, Philips Lighting, Philips Respironics, Cephalon, and ResMed Foundation, and reimbursements for conference travel expenses from Vanda Pharmaceuticals. His institution has received equipment donations or other support from Optalert\u2122, Compumedics, and Tyco Healthcare. He has served as an expert witness and\/or consultant to shift work organizations. SMWR also serves as a Program Leader in the Cooperative Research Centre for Alertness, Safety and Productivity. S.W.L. has no conflicts of interests related to the research or results reported in this paper. He is a Program Leader for the Cooperative Research Centre for Alertness Safety and Productivity. In the interests of full disclosure, commercial interests from the last 3 years (2015\u20132018) are listed below. S.W.L. has received consulting fees from the Atlanta Falcons, Atlanta Hawks, Consumer Sleep Solutions, Noble Insights, OpTerra Energy Services Inc., Pegasus Capital Advisors LP, Serrado Capital, Slingshot Insights and Team C Racing and has current consulting contracts with Akili Interactive, Apex 2100 Ltd, Delos Living LLC, Headwaters Inc., Hintsa Performance AG, Light Cognitive, Lighting Science Group Corporation, Mental Workout, PlanLED, Six Senses, and Wyle Integrated Science and Engineering. SWL has received unrestricted equipment gifts from Biological Illuminations LLC, Bionetics Corporation and F.LUX Software LLC; has equity in iSLEEP, Pty; advance author payment and\/or royalties from Oxford University Press; honoraria plus travel, accommodation and\/or meals for invited seminars, conference presentations or teaching from BHP Billiton, Estee Lauder, Informa Exhibitions (USGBC), and Teague; travel, accommodation and\/or meals only (no honoraria) for invited seminars, conference presentations or teaching from Lightfair, U.S.G.B.C., D.I.N. and S.L.T.B.R. and S.W.L. has completed investigator-initiated research grants from Biological Illumination LLC and has an ongoing investigator initiated grant from F. Lux Software LLC; S.W.L. holds a process patent for \u2018Systems and methods for determining and\/or controlling sleep quality\u2019, which is assigned to the Brigham and Women\u2019s Hospital per Hospital policy. S.W.L. has also served as a paid expert on behalf of several public bodies on arbitrations related to work hours and legal proceedings related to light and health. C.A. has received a research award\/prize from Sanofi-Aventis; contract research support from VicRoads, Rio Tinto Coal Australia, National Transport Commission, Tontine\/Pacific Brands and VicRoads; and lecturing fees from Brown Medical School\/Rhode Island Hospital, Ausmed, Healthmed and TEVA Pharmaceuticals; and reimbursements for conference travel expenses from Philips Healthcare. In addition, she has served as a consultant through her institution to the Rail, Bus and Tram Union, the Transport Accident Commission (TAC) and the National Transportation Committee (NTC). She has also served as an expert witness and\/or consultant in relation to fatigue and drowsy driving. C.A. is a Theme Leader in the Cooperative Research Centre for Alertness, Safety and Productivity.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"4428"}}