ArticleCell reports. Medicine2022
Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study.
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Article in Cell reports. Medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed, 85 citations in OpenAlex.
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- TyG-Centered Endocrine-Metabolic Architecture in Patients with Thyroid Dysfunction: A Systems Phenotyping Study.Metabolites · 2026Article
- Genetic and molecular signatures highlight diverse pathways linking obesity to type 2 diabetes.Nature communications · 2026Article
- Plasma metabolite association profiles for type 2 diabetes genetic clusters in Finnish men.Diabetologia · 2026Article
- Five tenets for advancing evidence-based precision medicine.Nature medicine · 2026Review
- Diabetes mellitus as a multisystem disease: understanding subtypes, complications, and the link with steatotic liver diseases in humans.Hormones (Athens, Greece) · 2026Review
- Gut microbiota and metabolic disease risk in youth.Cell reports. Medicine · 2026Review
- The Extent and Phenotype of Coronary Artery Disease in Diabetes and Prediabetes: Insights From Imaging Studies and Potential Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Beyond Glucose-Rethinking Prediabetes for Precision Prevention.Diabetes care · 2026Review
- Aetiological clustering of newly diagnosed type 2 diabetes using machine learning: a retrospective cross-sectional study in Dubai, UAE.BMJ open · 2025Article
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- From omics to AI-mapping the pathogenic pathways in type 2 diabetes.FEBS letters · 2025Review
- Longitudinal Metabolic Trajectories in Diabetes Prevention Program Participants Reveal Subgroups With Varying Micro- and Macrovascular Complication Risks.Diabetes care · 2025Article
- Recognising, quantifying and accounting for classification uncertainty in type 2 diabetes subtypes.Diabetologia · 2025Observational
- Appraisal of Clinical Explanatory Variables in Subtyping of Type 2 Diabetes Using Machine Learning Models.Journal of clinical medicine · 2025Article
- Cohort profile of the Heidelberg study on diabetes and complications HEIST-DiC.Scientific reports · 2025Article
- Glyoxalase 1 Inducer,Antioxidants (Basel, Switzerland) · 2025Article
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Authors and funding
61 authors at 20 institutions in 10 countries.
Agata Wesolowska-AndersenWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Caroline A BrorssonDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Roberto BizzottoC.N.R. Institute of Neuroscience, Padova, Italy.
Andrea MariC.N.R. Institute of Neuroscience, Padova, Italy.
Andrea TuraC.N.R. Institute of Neuroscience, Padova, Italy.
Robert KoivulaWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Anubha MahajanWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Ana VinuelaDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Juan Fernandez TajesWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Sapna SharmaResearch Unit Molecular Endocrinology And Metabolism, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Mark HaidResearch Unit Molecular Endocrinology And Metabolism, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Cornelia PrehnResearch Unit Molecular Endocrinology And Metabolism, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Anna ArtatiResearch Unit Molecular Endocrinology And Metabolism, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Mun-Gwan HongAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden.
Petra B MusholtR&D Global Development, Translational Medicine & Clinical Pharmacology (TMCP), Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
Azra KurbasicUniversity of Lund, Clinical Sciences, Malmö, Sweden.
Federico De MasiDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Kostas TsirigosDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Helle Krogh PedersenDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Valborg GudmundsdottirDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Cecilia Engel ThomasDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Karina BanasikNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Chrisopher JennisonDepartment of Mathematical Sciences, University of Bath, Bath, UK.
Angus JonesUniversity of Exeter Medical School, Exeter, UK.
Gwen KennedyThe Immunoassay Biomarker Core Laboratory, Shool of Medicine, University of Dundee, Dundee, UK.
Jimmy BellResearch Centre for Optimal Health, Deparment of Life Sciences, University of Westminster, London, UK.
Louise ThomasResearch Centre for Optimal Health, Deparment of Life Sciences, University of Westminster, London, UK.
Gary FrostSection for Nutrition Research, Faculty of Medicine, Hammersmith Campus, Imperial College London, London, UK.
Henrik ThomsenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kristine AllinNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Tue Haldor HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Henrik VestergaardNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Femke RuttersDepartment of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, the Netherlands.
Petra EldersDepartment of General Practice, Amsterdam UMC-location VUmc, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Leen t'HartDepartment of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-location VUmc, Amsterdam, the Netherlands.
Amelie BonnefondINSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille University Hospital, Lille, France.
Mickaël CanouilINSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille University Hospital, Lille, France.
Soren BrageMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Tarja KokkolaDepartment of Medicine, University of Eastern Finland, Kuopio, Finland.
Alison HeggieInstitute of Cellular Medicine, Newcastle University, Newcastle, UK.
Donna McEvoyDiabetes Research Network, Royal Victoria Infirmary, Newcastle, UK.
Andrew HattersleyUniversity of Exeter Medical School, Exeter, UK.
Timothy McDonaldUniversity of Exeter Medical School, Exeter, UK.
Harriet TeareCentre for Health, Law and Emerging Technologies (HeLEX), Faculty of Law, University of Oxford, Oxford, UK.
Martin RidderstraleUniversity of Lund, Clinical Sciences, Malmö, Sweden.
Mark WalkerTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
Ian ForgieUniversity of Dundee, Dundee, UK.
Giuseppe N GiordanoR&D Global Development, Translational Medicine & Clinical Pharmacology (TMCP), Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
Philippe FroguelINSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille University Hospital, Lille, France.
Imre PavoEli Lilly Regional Operations GmbH, Vienna, Austria.
Hartmut RuettenR&D Global Development, Translational Medicine & Clinical Pharmacology (TMCP), Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Emmanouil DermitzakisDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Paul W FranksUniversity of Lund, Clinical Sciences, Malmö, Sweden.
Jochen M SchwenkAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden.
Jerzy AdamskiResearch Unit Molecular Endocrinology And Metabolism, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Ewan PearsonUniversity of Dundee, Dundee, UK.
Mark I McCarthyWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Søren BrunakDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
IMI DIRECT Consortium
University of Copenhagen · DKCentre for Human Genetics · GBTechnical University of Denmark · DKHelmholtz Zentrum München · DECentre National de la Recherche Scientifique · FRNeuroscience Institute · ITSanofi (Germany) · DEUniversity of Dundee · GBUniversity of Exeter · GBAmsterdam University Medical Centers · NLNewcastle University · GBScience for Life Laboratory · SEUniversity of Geneva · CHUniversity of Westminster · GBHammersmith Hospital · GBLeiden University Medical Center · NLNational University of Singapore · SGRoyal Victoria Infirmary · GBUniversity of Bath · GBUniversity of Cambridge · GB
Funding
Integrating genome-scale data to reveal causal mechanisms in type 2 diabetesU01DK105535 · NIDDK · UNIVERSITY OF OXFORD · PI GLOYN, ANNA LOUISE · 2015 to 2019
$1.7MMedical Research Council MC_UU_00006/4Medical Research Council MC_UU_12015/3Medical Research Council MR/X001210/1NIDDK NIH HHS U01 DK105535Wellcome Trust 090532Wellcome Trust 098381Wellcome Trust 102820/Z/13/ZWellcome Trust 106130Wellcome Trust 203141Wellcome Trust 212259
Abstract
The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments.
Indexed as
AdultDiabetes Mellitus, Type 2Disease ProgressionFemaleFollow-Up StudiesGenetic Predisposition to DiseaseGenomicsHumansMaleMiddle AgedPhenotypeRisk Factorsarchetypesdisease progressionglycaemic deteriorationmulti-omicspatient clusteringpatient stratificationprecision medicinesoft-clusteringtype 2 diabetes
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