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Slieker, R.C.* ; Donnelly, L.A.* ; Akalestou, E.* ; Lopez-Noriega, L.* ; Melhem, R.* ; Güneş, A.* ; Abou Azar, F.* ; Efanov, A.* ; Georgiadou, E.* ; Muniangi-Muhitu, H.* ; Sheikh, M.* ; Giordano, G.N.* ; Åkerlund, M.* ; Ahlqvist, E.* ; Ali, A.* ; Banasik, K.* ; Brunak, S.* ; Barovic, M. ; Bouland, G.A.* ; Burdet, F.* ; Canouil, M.* ; Dragan, I.* ; Elders, P.J.M.* ; Fernandez, C.* ; Festa, A.* ; Fitipaldi, H.* ; Froguel, P.* ; Gudmundsdottir, V.* ; Gudnason, V.* ; Gerl, M.J.* ; van der Heijden, A.A.* ; Jennings, L.L.* ; Hansen, M.K.* ; Kim, M.* ; Leclerc, I.* ; Klose, C.* ; Kuznetsov, D.* ; Mansour Aly, D.* ; Mehl, F.* ; Marek, D.* ; Melander, O.* ; Niknejad, A.* ; Ottosson, F.* ; Pavo, I.* ; Duffin, K.C.* ; Syed, S.K.* ; Shaw, J.L.* ; Cabrera, O.* ; Pullen, T.J.* ; Simons, K.* ; Solimena, M. ; Suvitaival, T.* ; Wretlind, A.* ; Rossing, P.* ; Lyssenko, V.* ; Legido Quigley, C.* ; Groop, L.* ; Thorens, B.* ; Franks, P.W.* ; Lim, G.E.* ; Estall, J.* ; Ibberson, M.* ; Beulens, J.W.J.* ; ’t Hart, L.M.* ; Pearson, E.R.* ; Rutter, G.A.*

Identification of biomarkers for glycaemic deterioration in type 2 diabetes.

Nat. Commun. 14:2533 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 2-aminoadipic Acid; Obese Women; Weight-loss; Protein; Receptor; Expression; Homocitrulline; Association; Deficiency; Metabolism
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 14, Issue: 1, Pages: , Article Number: 2533 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
Grants Faculty of Medicine at Lund University
Swedish Research Council
Swedish Foundation for Strategic Research
Wellcome Trust New Investigator Award
Wellcome Trust Investigator Award
MRC
Experimental Challenge Grant (DIVA)
Diabetes UK Project
Canada Research Chair in Adipocyte Development
Swedish governmental funding of clinical research (ALF)
Vinnova Swelife
Innovative Medicines Initiative 2 Joint Undertaking
Innovation Canada
European Union
EFPIA
Swiss State Secretariat for Education, Research and Innovation (SERI)
Icelandic Research Fund
Netherlands Organisation for Health Research and Development
CIHR
Wellcome Trust
CIHR Project Grant