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Identification of biomarkers for glycaemic deterioration in type 2 diabetes.
Slieker, Roderick C; Donnelly, Louise A; Akalestou, Elina; Lopez-Noriega, Livia; Melhem, Rana; Günes, Aysim; Abou Azar, Frederic; Efanov, Alexander; Georgiadou, Eleni; Muniangi-Muhitu, Hermine; Sheikh, Mahsa; Giordano, Giuseppe N; Åkerlund, Mikael; Ahlqvist, Emma; Ali, Ashfaq; Banasik, Karina; Brunak, Søren; Barovic, Marko; Bouland, Gerard A; Burdet, Frédéric; Canouil, Mickaël; Dragan, Iulian; Elders, Petra J M; Fernandez, Celine; Festa, Andreas; Fitipaldi, Hugo; Froguel, Phillippe; Gudmundsdottir, Valborg; Gudnason, Vilmundur; Gerl, Mathias J; van der Heijden, Amber A; Jennings, Lori L; Hansen, Michael K; Kim, Min; Leclerc, Isabelle; Klose, Christian; Kuznetsov, Dmitry; Mansour Aly, Dina; Mehl, Florence; Marek, Diana; Melander, Olle; Niknejad, Anne; Ottosson, Filip; Pavo, Imre; Duffin, Kevin; Syed, Samreen K; Shaw, Janice L; Cabrera, Over; Pullen, Timothy J; Simons, Kai.
Afiliação
  • Slieker RC; Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam Cardiovascular Sciences, Amsterdam UMC, location VUMC, Amsterdam, the Netherlands.
  • Donnelly LA; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
  • Akalestou E; Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK.
  • Lopez-Noriega L; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Melhem R; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Günes A; CHUM Research Centre and University of Montreal, Montreal, QC, Canada.
  • Abou Azar F; IRCM and University of Montreal, Montreal, QC, Canada.
  • Efanov A; CHUM Research Centre and University of Montreal, Montreal, QC, Canada.
  • Georgiadou E; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, US.
  • Muniangi-Muhitu H; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Sheikh M; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Giordano GN; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Åkerlund M; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Ahlqvist E; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Ali A; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Banasik K; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Brunak S; Novo Nordisk Foundation Center for Protein Research, Copenhagen, Denmark.
  • Barovic M; Novo Nordisk Foundation Center for Protein Research, Copenhagen, Denmark.
  • Bouland GA; Paul Langerhans Institute Dresden (PLID) of the Helmholtz Center Munich at the University Hospital Carl Gustav Carus and Medical Faculty, Dresden, Germany.
  • Burdet F; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
  • Canouil M; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Dragan I; INSERM U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille University Hospital, Lille, F-59000, France.
  • Elders PJM; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Fernandez C; Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, the Netherlands.
  • Festa A; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Fitipaldi H; Eli Lilly Regional Operations GmbH, Vienna, Austria.
  • Froguel P; 1st Medical Department, LK Stockerau, Niederösterreich, Austria.
  • Gudmundsdottir V; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Gudnason V; INSERM U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille University Hospital, Lille, F-59000, France.
  • Gerl MJ; Division of Systems Biology, Department of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK.
  • van der Heijden AA; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Jennings LL; Icelandic Heart Association, Kopavogur, Iceland.
  • Hansen MK; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Kim M; Icelandic Heart Association, Kopavogur, Iceland.
  • Leclerc I; Lipotype GmbH, Dresden, Germany.
  • Klose C; Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, the Netherlands.
  • Kuznetsov D; Novartis Institutes for Biomedical Research, Cambridge, MA, 02139, USA.
  • Mansour Aly D; Cardiovascular and Metabolic Disease Research, Janssen Research & Development, Spring House, PA, USA.
  • Mehl F; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Marek D; Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicines, King's College London, London, UK.
  • Melander O; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Niknejad A; CHUM Research Centre and University of Montreal, Montreal, QC, Canada.
  • Ottosson F; Lipotype GmbH, Dresden, Germany.
  • Pavo I; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Duffin K; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Syed SK; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Shaw JL; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Cabrera O; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Pullen TJ; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Simons K; Department of Clinical Sciences, Lund University, Malmö, Sweden.
Nat Commun ; 14(1): 2533, 2023 05 03.
Article em En | MEDLINE | ID: mdl-37137910
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 422;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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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Ilhotas Pancreáticas / Diabetes Mellitus Tipo 2 Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Ilhotas Pancreáticas / Diabetes Mellitus Tipo 2 Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Holanda