@article{slieker_identification_2023,
	title = {Identification of biomarkers for glycaemic deterioration in type 2 diabetes},
	volume = {14},
	issn = {2041-1723},
	url = {https://www.nature.com/articles/s41467-023-38148-7},
	doi = {10.1038/s41467-023-38148-7},
	abstract = {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 {\textasciitilde}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.},
	language = {en},
	number = {1},
	urldate = {2023-05-04},
	journal = {Nature Communications},
	author = {Slieker, Roderick C. and Donnelly, Louise A. and Akalestou, Elina and Lopez-Noriega, Livia and Melhem, Rana and Güneş, Ayşim and Abou Azar, Frederic and Efanov, Alexander and Georgiadou, Eleni and Muniangi-Muhitu, Hermine and Sheikh, Mahsa and Giordano, Giuseppe N. and Åkerlund, Mikael and Ahlqvist, Emma and Ali, Ashfaq and Banasik, Karina and Brunak, Søren and Barovic, Marko and Bouland, Gerard A. and Burdet, Frédéric and Canouil, Mickaël and Dragan, Iulian and Elders, Petra J. M. and Fernandez, Celine and Festa, Andreas and Fitipaldi, Hugo and Froguel, Phillippe and Gudmundsdottir, Valborg and Gudnason, Vilmundur and Gerl, Mathias J. and van der Heijden, Amber A. and Jennings, Lori L. and Hansen, Michael K. and Kim, Min and Leclerc, Isabelle and Klose, Christian and Kuznetsov, Dmitry and Mansour Aly, Dina and Mehl, Florence and Marek, Diana and Melander, Olle and Niknejad, Anne and Ottosson, Filip and Pavo, Imre and Duffin, Kevin and Syed, Samreen K. and Shaw, Janice L. and Cabrera, Over and Pullen, Timothy J. and Simons, Kai and Solimena, Michele and Suvitaival, Tommi and Wretlind, Asger and Rossing, Peter and Lyssenko, Valeriya and Legido Quigley, Cristina and Groop, Leif and Thorens, Bernard and Franks, Paul W. and Lim, Gareth E. and Estall, Jennifer and Ibberson, Mark and Beulens, Joline W. J. and ’t Hart, Leen M and Pearson, Ewan R. and Rutter, Guy A.},
	month = may,
	year = {2023},
	pages = {2533},
}