دورية أكاديمية
Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study.
| العنوان: | Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study. |
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| المؤلفون: | Slieker RC; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands., Donnelly LA; Population Health & Genomics, School of Medicine, University of Dundee, Dundee, U.K., Fitipaldi H; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SUS, Malmö, Sweden., Bouland GA; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands., Giordano GN; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SUS, Malmö, Sweden., Åkerlund M; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SUS, Malmö, Sweden., Gerl MJ; Lipotype GmbH, Dresden, Germany., Ahlqvist E; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SUS, Malmö, Sweden., Ali A; Steno Diabetes Center Copenhagen, Gentofte, Denmark., Dragan I; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Elders P; Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands., Festa A; Eli Lilly Regional Operations GmbH, Vienna, Austria.; 1st Medical Department, LK Stockerau, Niederösterreich, Austria., Hansen MK; Cardiovascular and Metabolic Disease Research, Janssen Research & Development, Spring House, PA., van der Heijden AA; Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands., Mansour Aly D; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SUS, Malmö, Sweden., Kim M; Steno Diabetes Center Copenhagen, Gentofte, Denmark.; Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicines, King's College London, London, U.K., Kuznetsov D; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Mehl F; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Klose C; Lipotype GmbH, Dresden, Germany., Simons K; Lipotype GmbH, Dresden, Germany., Pavo I; Eli Lilly Regional Operations GmbH, Vienna, Austria., Pullen TJ; Department of Diabetes, Guy's Campus, King's College London, London, U.K.; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, U.K., 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.; Cardiovascular and Metabolic Disease Research, Janssen Research & Development, Spring House, PA., Groop L; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SUS, Malmö, Sweden.; Finnish Institute of Molecular Medicine, Helsinki University, Helsinki, Finland., Thorens B; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland., Franks PW; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SUS, Malmö, Sweden.; Department of Nutrition, Harvard School of Public Health, Boston, MA., Ibberson M; Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Rutter GA; Department of Diabetes, Guy's Campus, King's College London, London, U.K.; Lee Kong Chian School of Medicine, Nan Yang Technological University, Singapore., Beulens JWJ; Department of Epidemiology and Data Science, Amsterdam Public Health Institute, 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 Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands lmthart@lumc.nl e.z.pearson@dundee.ac.uk.; Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands., Pearson ER; Population Health & Genomics, School of Medicine, University of Dundee, Dundee, U.K. lmthart@lumc.nl e.z.pearson@dundee.ac.uk. |
| المصدر: | Diabetes [Diabetes] 2021 Nov; Vol. 70 (11), pp. 2683-2693. Date of Electronic Publication: 2021 Aug 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | Diabetes Mellitus, Type 2/*metabolism, Cluster Analysis ; Cohort Studies ; Cross-Sectional Studies ; Humans ; Insulin Resistance |
| مستخلص: | Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of a previous study clustered people with diabetes according to five diabetes subtypes. The aim of the current study is to investigate the etiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic ( N = 12,828), metabolomic ( N = 2,945), lipidomic ( N = 2,593), and proteomic ( N = 1,170) data were obtained in plasma. For each data type, each cluster was compared with the other four clusters as the reference. The insulin-resistant cluster showed the most distinct molecular signature, with higher branched-chain amino acid, diacylglycerol, and triacylglycerol levels and aberrant protein levels in plasma were enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher levels of cytokines. The mild diabetes cluster with high HDL showed the most beneficial molecular profile with effects opposite of those seen in the insulin-resistant cluster. This study shows that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease. (© 2021 by the American Diabetes Association.) |
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| معلومات مُعتمدة: | United Kingdom WT_ Wellcome Trust; 102820/Z/13/Z United Kingdom WT_ Wellcome Trust; WT098424AIA United Kingdom WT_ Wellcome Trust; 212625/Z/18/Z United Kingdom WT_ Wellcome Trust; MR/R022259/1 United Kingdom MRC_ Medical Research Council; MR/J0003042/1 United Kingdom MRC_ Medical Research Council; MR/L020149/1 United Kingdom MRC_ Medical Research Council |
| سلسلة جزيئية: | figshare 10.2337/figshare.15113193 |
| تواريخ الأحداث: | Date Created: 20210811 Date Completed: 20211229 Latest Revision: 20211229 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8564413 |
| DOI: | 10.2337/db20-1281 |
| PMID: | 34376475 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
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| DOI: | 10.2337/db20-1281 |