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)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
2-aminoadipic Acid; Obese Women; Weight-loss; Protein; Receptor; Expression; Homocitrulline; Association; Deficiency; Metabolism
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2023
Prepublished im Jahr
0
HGF-Berichtsjahr
2023
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 14,
Heft: 1,
Seiten: ,
Artikelnummer: 2533
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502600-001
Förderungen
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
Copyright
Erfassungsdatum
2023-11-27