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dc.contributor.authorHosking, Joanne
dc.contributor.authorPinkney, Jonathan
dc.contributor.authorJeffery, Alison
dc.contributor.authorCominetti, O
dc.contributor.authorDa Silva, L
dc.contributor.authorCollino, S
dc.contributor.authorKussmann, M
dc.contributor.authorHager, J
dc.contributor.authorMartin, F
dc.date.accessioned2020-01-23T13:01:10Z
dc.date.issued2019-11
dc.identifier.issn1399-543X
dc.identifier.issn1399-5448
dc.identifier.urihttp://hdl.handle.net/10026.1/15339
dc.description.abstract

BACKGROUND: While insulin resistance (IR) is associated with specific metabolite signatures in adults, there have been few truly longitudinal studies in healthy children, either to confirm which abnormalities are present, or to determine whether they precede or result from IR. Therefore, we investigated the association of serum metabolites with IR in childhood in the Earlybird cohort. METHODS: The Earlybird cohort is a well-characterized cohort of healthy children with annual measurements from age 5 to 16 years. For the first time, longitudinal association analyses between individual serum metabolites and homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) have been performed taking into account the effects of age, growth, puberty, adiposity, and physical activity. RESULTS: IR was higher in girls than in boys and was associated with increasing body mass index (BMI). In longitudinal analysis IR was associated with reduced concentrations of branched-chain amino acids (BCAA), 2-ketobutyrate, citrate and 3-hydroxybutyrate, and higher concentrations of lactate and alanine. These findings demonstrate the widespread biochemical consequences of IR for intermediary metabolism, ketogenesis, and pyruvate oxidation during normal child growth and development. CONCLUSIONS: Longitudinal analysis can differentiate metabolite signatures that precede or follow the development of greater levels of IR. In healthy normal weight children, higher levels of IR are associated with reduced levels of BCAA, ketogenesis, and fuel oxidation. In contrast, elevated lactate concentrations preceded the rise in IR. These changes reveal the metabolite signature of insulin action during normal growth, and they contrast with previous findings in obese children and adults that represent the consequences of IR and obesity.

dc.format.extent832-841
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoen
dc.publisherWiley
dc.subjectamino acids
dc.subjectbiochemistry
dc.subjectinsulin resistance
dc.subjectlongitudinal
dc.subjectphenotyping
dc.titleInsulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72)
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000474896100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue7
plymouth.volume20
plymouth.publication-statusPublished
plymouth.journalPediatric Diabetes
dc.identifier.doi10.1111/pedi.12884
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA03 Allied Health Professions, Dentistry, Nursing and Pharmacy
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/FoH - Community and Primary Care
plymouth.organisational-group/Plymouth/Research Groups/Institute of Health and Community
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBBB
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CCT&PS
plymouth.organisational-group/Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR)
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeDenmark
dcterms.dateAccepted2019-06-19
dc.rights.embargodate2020-6-28
dc.identifier.eissn1399-5448
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1111/pedi.12884
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review


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