Multi-omics subgroups associated with glycaemic deterioration in type 2 diabetes: an IMI-RHAPSODY Study
Frontiers in Endocrinology, vol. 15, pp. 1350796
Abstract
Introduction: Type 2 diabetes (T2D) onset, progression and outcomes differ substantially between individuals. Multi-omics analyses may allow a deeper understanding of these differences and ultimately facilitate personalised treatments. Here, in an unsupervised "bottom-up" approach, we attempt to group T2D patients based solely on -omics data generated from plasma. Methods: Circulating plasma lipidomic and proteomic data from two independent clinical cohorts, Hoorn Diabetes Care System (DCS) and Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS), were analysed using Similarity Network Fusion. The resulting patient network was analysed with Logistic and Cox regression modelling to explore relationships between plasma -omic profiles and clinical characteristics. Results: =3.7e-11;2.5e-06, DCS and GoDARTS, respectively; Homeostatic model assessment 2 (HOMA2)-B; -IR; -S, p=0.0008;4.2e-11;1.1e-09, only in DCS). The main molecular signatures separating the two groups included triacylglycerols, sphingomyelin, testican-1 and interleukin 18 receptor. Conclusions: Using an unsupervised network-based fusion method on plasma lipidomics and proteomics data from two independent cohorts, we were able to identify two subgroups of T2D patients differing in terms of disease severity. The molecular signatures identified within these subgroups provide insights into disease mechanisms and possibly new prognostic markers for T2D.
Authors 17
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Centre Hospitalier de l’Université de Montréal · Université de Montréal
Affiliation as printed
Centre de Recherche du CHUM, Faculty of Medicine, University of Montreal, Montreal, QC, Canada
Centre de Recherche du CHUM, Faculty of Medicine, University of Montreal, Canada
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SIB Swiss Institute of Bioinformatics
Affiliation as printed
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Switzerland
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SIB Swiss Institute of Bioinformatics
Affiliation as printed
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Switzerland
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Affiliation as printed
Section of Cell Biology and Functional Genomics, Department of Metabolism, Diabetes and Reproduction, Imperial College of London, London, United Kingdom
Section of Cell Biology and Functional Genomics, Department of Metabolism, Diabetes and Reproduction, Imperial College of London, London, United Kingdom,
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Janssen Research & Development (United States)
Affiliation as printed
Janssen Research and Development, Philadelphia, PA, United States
Janssen Research and Development, Philadelphia, PA, United States,
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Amsterdam Public Health · Amsterdam University Medical Centers
Affiliation as printed
Amsterdam Public Health, Amsterdam, Netherlands
Department of Epidemiology and Data Sciences, Amsterdam University Medical Center, Amsterdam, Netherlands
Department of Epidemiology and Data Sciences, Amsterdam University Medical Center, Netherlands
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Leen M. ‘t Hart Aachen Department of Biomedical Data Sciences Section Molecular Epidemiology Department of Cell and Chemical Biology
Leiden University Medical Center · Amsterdam Public Health · Amsterdam University Medical Centers
Affiliation as printed
Amsterdam Public Health, Amsterdam, Netherlands
Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
Department of Epidemiology and Data Sciences, Amsterdam University Medical Center, Amsterdam, Netherlands
Amsterdam Public Health, Amsterdam, Netherlands,
Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands,
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands,
Department of Epidemiology and Data Sciences, Amsterdam University Medical Center, Amsterdam, Netherlands,
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
Department of Cell and Chemical Biology, Leiden University Medical Center, Netherlands
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Affiliation as printed
Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom,
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Affiliation as printed
Lipotype GmbH, Dresden, Germany
Lipotype GmbH, Germany
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Affiliation as printed
Lipotype GmbH, Dresden, Germany
Lipotype GmbH, Dresden, Germany,
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SIB Swiss Institute of Bioinformatics
Affiliation as printed
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Switzerland
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Affiliation as printed
Lipotype GmbH, Dresden, Germany
Lipotype GmbH, Germany
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Amsterdam Public Health · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, Netherlands
Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, Netherlands,
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Affiliation as printed
Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
Division of Population Health & Genomics, School of Medicine, University of Dundee, United Kingdom
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Guy A. Rutter corresponding
Nanyang Technological University · Centre Hospitalier de l’Université de Montréal · Imperial College London · Université de Montréal
Affiliation as printed
Centre de Recherche du CHUM, Faculty of Medicine, University of Montreal, Montreal, QC, Canada
Lee Kong Chian School of Medicine, Nan Yang Technological University, Singapore, Singapore
Section of Cell Biology and Functional Genomics, Department of Metabolism, Diabetes and Reproduction, Imperial College of London, London, United Kingdom
Centre de Recherche du CHUM, Faculty of Medicine, University of Montreal, Canada
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Mark R. Ibberson corresponding
SIB Swiss Institute of Bioinformatics
Affiliation as printed
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
Vital-IT Group, SIB Swiss Institute of Bioinformatics, Switzerland
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