Identification of biomarkers for glycaemic deterioration in type 2 diabetes
dc.contributor.author | Slieker, Roderick C. | |
dc.contributor.author | Donnelly, Louise A. | |
dc.contributor.author | Akalestou, Elina | |
dc.contributor.author | Lopez-Noriega, Livia | |
dc.contributor.author | Melhem, Rana | |
dc.contributor.author | Güneş, Ayşim | |
dc.contributor.author | Abou Azar, Frederic | |
dc.contributor.author | Efanov, Alexander | |
dc.contributor.author | Georgiadou, Eleni | |
dc.contributor.author | Muniangi-Muhitu, Hermine | |
dc.contributor.author | Sheikh, Mahsa | |
dc.contributor.author | Giordano, Giuseppe N. | |
dc.contributor.author | Åkerlund, Mikael | |
dc.contributor.author | Ahlqvist, Emma | |
dc.contributor.author | Ali, Ashfaq | |
dc.contributor.author | Banasik, Karina | |
dc.contributor.author | Brunak, Søren | |
dc.contributor.author | Barovic, Marko | |
dc.contributor.author | Bouland, Gerard A. | |
dc.contributor.author | Burdet, Frédéric | |
dc.contributor.author | Canouil, Mickaël | |
dc.contributor.author | Dragan, Iulian | |
dc.contributor.author | Elders, Petra J. M. | |
dc.contributor.author | Fernandez, Celine | |
dc.contributor.author | Festa, Andreas | |
dc.contributor.author | Fitipaldi, Hugo | |
dc.contributor.author | Froguel, Phillippe | |
dc.contributor.author | Gudmundsdottir, Valborg | |
dc.contributor.author | Gudnason, Vilmundur | |
dc.contributor.author | Gerl, Mathias J. | |
dc.contributor.author | van der Heijden, Amber A. | |
dc.contributor.author | Jennings, Lori L. | |
dc.contributor.author | Hansen, Michael K. | |
dc.contributor.author | Kim, Min | |
dc.contributor.author | Leclerc, Isabelle | |
dc.contributor.author | Klose, Christian | |
dc.contributor.author | Kuznetsov, Dmitry | |
dc.contributor.author | Mansour Aly, Dina | |
dc.contributor.author | Mehl, Florence | |
dc.contributor.author | Marek, Diana | |
dc.contributor.author | Melander, Olle | |
dc.contributor.author | Niknejad, Anne | |
dc.contributor.author | Ottosson, Filip | |
dc.contributor.author | Pavo, Imre | |
dc.contributor.author | Duffin, Kevin | |
dc.contributor.author | Syed, Samreen K. | |
dc.contributor.author | Shaw, Janice L. | |
dc.contributor.author | Cabrera, Over | |
dc.contributor.author | Pullen, Timothy J. | |
dc.contributor.author | Simons, Kai | |
dc.contributor.author | Solimena, Michele | |
dc.contributor.author | Suvitaival, Tommi | |
dc.contributor.author | Wretlind, Asger | |
dc.contributor.author | Rossing, Peter | |
dc.contributor.author | Lyssenko, Valeriya | |
dc.contributor.author | Legido Quigley, Cristina | |
dc.contributor.author | Groop, Leif | |
dc.contributor.author | Thorens, Bernard | |
dc.contributor.author | Franks, Paul W. | |
dc.contributor.author | Lim, Gareth E. | |
dc.contributor.author | Estall, Jennifer | |
dc.contributor.author | Ibberson, Mark | |
dc.contributor.author | Beulens, Joline W. J. | |
dc.contributor.author | ’t Hart, Leen M | |
dc.contributor.author | Pearson, Ewan R. | |
dc.contributor.author | Rutter, Guy A. | |
dc.date.accessioned | 2023-09-29T11:50:29Z | |
dc.date.available | 2023-09-29T11:50:29Z | |
dc.date.created | 2023-06-09T11:09:39Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://hdl.handle.net/11250/3093115 | |
dc.description.abstract | We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Nature | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Identification of biomarkers for glycaemic deterioration in type 2 diabetes | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2023 The Author(s) | en_US |
dc.source.articlenumber | 2533 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.doi | 10.1038/s41467-023-38148-7 | |
dc.identifier.cristin | 2153282 | |
dc.source.journal | Nature Communications | en_US |
dc.identifier.citation | Nature Communications. 2023, 14 (1), 2533. | en_US |
dc.source.volume | 14 | en_US |
dc.source.issue | 1 | en_US |
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