%0 Journal Article
%T Identification of biomarkers for glycaemic deterioration in type 2 diabetes
%V 14
%N 1
%P 2533
%U https://www.nature.com/articles/s41467-023-38148-7
%X 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.
%G en
%J Nature Communications
%A Slieker, Roderick C.
%A Donnelly, Louise A.
%A Akalestou, Elina
%A Lopez-Noriega, Livia
%A Melhem, Rana
%A Güneş, Ayşim
%A Abou Azar, Frederic
%A Efanov, Alexander
%A Georgiadou, Eleni
%A Muniangi-Muhitu, Hermine
%A Sheikh, Mahsa
%A Giordano, Giuseppe N.
%A Åkerlund, Mikael
%A Ahlqvist, Emma
%A Ali, Ashfaq
%A Banasik, Karina
%A Brunak, Søren
%A Barovic, Marko
%A Bouland, Gerard A.
%A Burdet, Frédéric
%A Canouil, Mickaël
%A Dragan, Iulian
%A Elders, Petra J. M.
%A Fernandez, Celine
%A Festa, Andreas
%A Fitipaldi, Hugo
%A Froguel, Phillippe
%A Gudmundsdottir, Valborg
%A Gudnason, Vilmundur
%A Gerl, Mathias J.
%A van der Heijden, Amber A.
%A Jennings, Lori L.
%A Hansen, Michael K.
%A Kim, Min
%A Leclerc, Isabelle
%A Klose, Christian
%A Kuznetsov, Dmitry
%A Mansour Aly, Dina
%A Mehl, Florence
%A Marek, Diana
%A Melander, Olle
%A Niknejad, Anne
%A Ottosson, Filip
%A Pavo, Imre
%A Duffin, Kevin
%A Syed, Samreen K.
%A Shaw, Janice L.
%A Cabrera, Over
%A Pullen, Timothy J.
%A Simons, Kai
%A Solimena, Michele
%A Suvitaival, Tommi
%A Wretlind, Asger
%A Rossing, Peter
%A Lyssenko, Valeriya
%A Legido Quigley, Cristina
%A Groop, Leif
%A Thorens, Bernard
%A Franks, Paul W.
%A Lim, Gareth E.
%A Estall, Jennifer
%A Ibberson, Mark
%A Beulens, Joline W. J.
%A ’t Hart, Leen M
%A Pearson, Ewan R.
%A Rutter, Guy A.
%D 2023-05-03