Identification of biomarkers for glycaemic deterioration in type 2 diabetes.

Autor: Slieker RC; Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam Cardiovascular Sciences, Amsterdam UMC, location VUMC, Amsterdam, the Netherlands.; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands., Donnelly LA; Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK., Akalestou E; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, 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; CHUM Research Centre and University of Montreal, Montreal, QC, Canada., Güneş A; IRCM and University of Montreal, Montreal, QC, Canada., Abou Azar F; CHUM Research Centre and University of Montreal, Montreal, QC, Canada., Efanov A; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, US., Georgiadou E; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK., 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; Department of Clinical Sciences, Lund University, Malmö, Sweden., Åkerlund M; Department of Clinical Sciences, Lund University, Malmö, Sweden., Ahlqvist E; Department of Clinical Sciences, Lund University, Malmö, Sweden., Ali A; Steno Diabetes Center Copenhagen, Gentofte, Denmark., Banasik K; Novo Nordisk Foundation Center for Protein Research, Copenhagen, Denmark., Brunak S; Novo Nordisk Foundation Center for Protein Research, Copenhagen, Denmark., Barovic M; Paul Langerhans Institute Dresden (PLID) of the Helmholtz Center Munich at the University Hospital Carl Gustav Carus and Medical Faculty, Dresden, Germany., Bouland GA; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands., Burdet F; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Canouil M; 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., Dragan I; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Elders PJM; Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, the Netherlands., Fernandez C; Department of Clinical Sciences, Lund University, Malmö, Sweden., Festa A; Eli Lilly Regional Operations GmbH, Vienna, Austria.; 1st Medical Department, LK Stockerau, Niederösterreich, Austria., Fitipaldi H; Department of Clinical Sciences, Lund University, Malmö, Sweden., Froguel P; 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.; Division of Systems Biology, Department of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK., Gudmundsdottir V; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Icelandic Heart Association, Kopavogur, Iceland., Gudnason V; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Icelandic Heart Association, Kopavogur, Iceland., Gerl MJ; Lipotype GmbH, Dresden, Germany., van der Heijden AA; Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, the Netherlands., Jennings LL; Novartis Institutes for Biomedical Research, Cambridge, MA, 02139, USA., Hansen MK; Cardiovascular and Metabolic Disease Research, Janssen Research & Development, Spring House, PA, USA., Kim M; Steno Diabetes Center Copenhagen, Gentofte, Denmark.; Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicines, King's College London, London, UK., Leclerc I; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.; CHUM Research Centre and University of Montreal, Montreal, QC, Canada., Klose C; Lipotype GmbH, Dresden, Germany., Kuznetsov D; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Mansour Aly D; Department of Clinical Sciences, Lund University, Malmö, Sweden., Mehl F; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Marek D; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Melander O; Department of Clinical Sciences, Lund University, Malmö, Sweden., Niknejad A; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Ottosson F; Department of Clinical Sciences, Lund University, Malmö, Sweden.; Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark., Pavo I; Eli Lilly Regional Operations GmbH, Vienna, Austria., Duffin K; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, US., Syed SK; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, US., Shaw JL; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, US., Cabrera O; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, US., Pullen TJ; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.; Department of Diabetes, Guy's Campus King's College London, London, UK., Simons K; Lipotype GmbH, Dresden, Germany., Solimena M; Paul Langerhans Institute Dresden (PLID) of the Helmholtz Center Munich at the University Hospital Carl Gustav Carus and Medical Faculty, Dresden, Germany.; Molecular Diabetology, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany., Suvitaival T; Steno Diabetes Center Copenhagen, Gentofte, Denmark., Wretlind A; Steno Diabetes Center Copenhagen, Gentofte, Denmark., Rossing P; Steno Diabetes Center Copenhagen, Gentofte, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Lyssenko V; Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway.; Genomics, Diabetes and Endocrinology Unit, Department of Clinical Sciences Malmö, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden., Legido Quigley C; Steno Diabetes Center Copenhagen, Gentofte, Denmark.; Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicines, King's College London, London, UK., Groop L; Department of Clinical Sciences, Lund University, Malmö, Sweden.; Finnish Institute of Molecular Medicine, Helsinki University, Helsinki, Finland., Thorens B; Center for Integrative Genomics, University of Lausanne, CH-1015, Lausanne, Switzerland., Franks PW; Department of Clinical Sciences, Lund University, Malmö, Sweden.; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA., Lim GE; CHUM Research Centre and University of Montreal, Montreal, QC, Canada., Estall J; IRCM and University of Montreal, Montreal, QC, Canada., Ibberson M; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Beulens JWJ; Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam Cardiovascular Sciences, Amsterdam UMC, location VUMC, Amsterdam, the Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands., 't Hart LM; Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam Cardiovascular Sciences, Amsterdam UMC, location VUMC, Amsterdam, the Netherlands. lmthart@lumc.nl.; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands. lmthart@lumc.nl.; Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. lmthart@lumc.nl., Pearson ER; Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK. E.Z.Pearson@dundee.ac.uk., Rutter GA; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. g.rutter@imperial.ac.uk.; CHUM Research Centre and University of Montreal, Montreal, QC, Canada. g.rutter@imperial.ac.uk.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. g.rutter@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 03; Vol. 14 (1), pp. 2533. Date of Electronic Publication: 2023 May 03.
DOI: 10.1038/s41467-023-38148-7
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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