Identification of biomarkers for glycaemic deterioration in type 2 diabetes

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Slieker, Roderick CAmsterdam UMC - Vrije Universiteit Amsterdam (author)

Identification of biomarkers for glycaemic deterioration in type 2 diabetes

Article/chapterEnglish2023

Publisher, publication year, extent ...

2023

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LIBRIS-ID:oai:lup.lub.lu.se:51a898b1-315b-4e9c-9a12-57c9db304341
https://lup.lub.lu.se/record/51a898b1-315b-4e9c-9a12-57c9db304341URI
https://doi.org/10.1038/s41467-023-38148-7DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Mice
Animals
Male
Diabetes Mellitus, Type 2/metabolism
Blood Glucose/metabolism
Islets of Langerhans/metabolism
Insulin/metabolism
Lipids
Biomarkers/metabolism
Cell Adhesion Molecules/metabolism
Extracellular Matrix Proteins/metabolism

Added entries (persons, corporate bodies, meetings, titles ...)

Donnelly, Louise AUniversity of Dundee (author)
Akalestou, ElinaImperial College London (author)
Lopez-Noriega, LiviaImperial College London (author)
Melhem, RanaUniversity of Montreal (author)
Güneş, AyşimUniversity of Montreal (author)
Abou Azar, FredericUniversity of Montreal (author)
Efanov, AlexanderEli Lilly and Company (author)
Georgiadou, EleniImperial College London (author)
Muniangi-Muhitu, HermineImperial College London (author)
Sheikh, Mahsa (author)
Giordano, Giuseppe NLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-geg (author)
Åkerlund, MikaelLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups(Swepub:lu)medk-mak (author)
Ahlqvist, EmmaLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)infl-eah (author)
Ali, AshfaqSteno Diabetes Center Copenhagen(Swepub:lu)cob-aaf (author)
Banasik, Karina (author)
Brunak, Søren (author)
Barovic, Marko (author)
Bouland, Gerard A (author)
Burdet, Frédéric (author)
Canouil, Mickaël (author)
Dragan, Iulian (author)
Elders, Petra J M (author)
Fernandez, CelineLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)tmb-cfe (author)
Festa, Andreas (author)
Fitipaldi, HugoLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)hu3745fi (author)
Froguel, Phillippe (author)
Gudmundsdottir, Valborg (author)
Gudnason, Vilmundur (author)
Gerl, Mathias J (author)
van der Heijden, Amber A (author)
Jennings, Lori L (author)
Hansen, Michael K (author)
Kim, Min (author)
Leclerc, Isabelle (author)
Klose, Christian (author)
Kuznetsov, Dmitry (author)
Mansour Aly, DinaLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)di3053ma (author)
Mehl, Florence (author)
Marek, Diana (author)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
Niknejad, Anne (author)
Ottosson, FilipLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Danish Serum Institute, Copenhagen(Swepub:lu)immu-flo (author)
Pavo, Imre (author)
Duffin, Kevin (author)
Syed, Samreen K (author)
Shaw, Janice L (author)
Cabrera, Over (author)
Pullen, Timothy J (author)
Simons, Kai (author)
Solimena, Michele (author)
Suvitaival, Tommi (author)
Wretlind, Asger (author)
Rossing, Peter (author)
Lyssenko, ValeriyaLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Bergen,Skåne University Hospital(Swepub:lu)endo-vly (author)
Legido Quigley, Cristina (author)
Groop, LeifLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki(Swepub:lu)endo-lgr (author)
Thorens, Bernard (author)
Franks, Paul WLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Harvard T.H. Chan School of Public Health(Swepub:lu)med-plf (author)
Lim, Gareth E (author)
Estall, Jennifer (author)
Ibberson, Mark (author)
Beulens, Joline W J (author)
't Hart, Leen M (author)
Pearson, Ewan R (author)
Rutter, Guy A (author)
Amsterdam UMC - Vrije Universiteit AmsterdamUniversity of Dundee (creator_code:org_t)

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In:Nature Communications14, s. 1-182041-1723

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By the author/editor: Slieker, Roderic ...; Donnelly, Louise ...; Akalestou, Elina; Lopez-Noriega, L ...; Melhem, Rana; Güneş, Ayşim; show more...; Abou Azar, Frede ...; Efanov, Alexande ...; Georgiadou, Elen ...; Muniangi-Muhitu, ...; Sheikh, Mahsa; Giordano, Giusep ...; Åkerlund, Mikael; Ahlqvist, Emma; Ali, Ashfaq; Banasik, Karina; Brunak, Søren; Barovic, Marko; Bouland, Gerard ...; Burdet, Frédéric; Canouil, Mickaël; Dragan, Iulian; Elders, Petra J ...; Fernandez, Celin ...; Festa, Andreas; Fitipaldi, Hugo; Froguel, Phillip ...; Gudmundsdottir, ...; Gudnason, Vilmun ...; Gerl, Mathias J; van der Heijden, ...; Jennings, Lori L; Hansen, Michael ...; Kim, Min; Leclerc, Isabell ...; Klose, Christian; Kuznetsov, Dmitr ...; Mansour Aly, Din ...; Mehl, Florence; Marek, Diana; Melander, Olle; Niknejad, Anne; Ottosson, Filip; Pavo, Imre; Duffin, Kevin; Syed, Samreen K; Shaw, Janice L; Cabrera, Over; Pullen, Timothy ...; Simons, Kai; Solimena, Michel ...; Suvitaival, Tomm ...; Wretlind, Asger; Rossing, Peter; Lyssenko, Valeri ...; Legido Quigley, ...; Groop, Leif; Thorens, Bernard; Franks, Paul W; Lim, Gareth E; Estall, Jennifer; Ibberson, Mark; Beulens, Joline ...; 't Hart, Leen M; Pearson, Ewan R; Rutter, Guy A; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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