Role of human plasma metabolites in prediabetes and type 2 diabetes from the IMI-DIRECT study
Our findings identify known BCAAs and lipids, along with novel N-lactoyl-amino acid metabolites, significantly associated with prediabetes and diabetes, that mediate the effect of diabetes from baseline to follow-up (18 and 48 months). Causal inference using genetic variants shows the role of lipid metabolism and n-3 fatty acids as being causal for metabolite-to-type 2 diabetes whereas the sum of hexoses is causal for type 2 diabetes-to-metabolite. Identified metabolite markers are useful for stratifying individuals based on their risk progression and should enable targeted interventions.
Authors
- Søren Brunak (ORCID: https://orcid.org/0000-0003-0316-5866)
- Robert W. Koivula (ORCID: https://orcid.org/0000-0002-1646-4163)
- Cornelia Prehn (ORCID: https://orcid.org/0000-0002-1274-4715)
- Juan Fernández‐Tajes (ORCID: https://orcid.org/0000-0003-1515-2421)
- Paul W. Franks (ORCID: https://orcid.org/0000-0002-0520-7604)
- Imre Pávó (ORCID: https://orcid.org/0000-0002-2016-7049)
- Giuseppe N. Giordano (ORCID: https://orcid.org/0000-0002-6719-6680)
- Jochen M. Schwenk (ORCID: https://orcid.org/0000-0001-8141-8449)
- Qiuling Dong (ORCID: https://orcid.org/0000-0002-3369-4120)
- Angus G. Jones (ORCID: https://orcid.org/0000-0002-0883-7599)
- Tarja Kokkola (ORCID: https://orcid.org/0000-0002-3303-3912)
- Jerzy Adamski (ORCID: https://orcid.org/0000-0001-9259-0199)
- Ana Viñuela (ORCID: https://orcid.org/0000-0003-3771-8537)
- Gabi Kastenmüller (ORCID: https://orcid.org/0000-0002-2368-7322)
- Mark Haid (ORCID: https://orcid.org/0000-0001-6118-1333)
- Harald Grallert (ORCID: https://orcid.org/0000-0002-6876-9655)
- Roberto Bizzotto (ORCID: https://orcid.org/0000-0002-8251-1730)
- Ewan R. Pearson (ORCID: https://orcid.org/0000-0001-9237-8585)
- Konstantinos D. Tsirigos (ORCID: https://orcid.org/0000-0001-5280-1107)
- Jonathan Adam
- Federico De Masi
- Manolis Dermitzakis
- Mark Walker (ORCID: https://orcid.org/0000-0002-2526-9810)
- Andrea Mari (ORCID: https://orcid.org/0000-0002-1436-5591)
- Timothy J. McDonald (ORCID: https://orcid.org/0000-0003-3559-6660)
- Mark I. McCarthy
- Hartmut Ruetten
- Anna Artati
- Andrea Tura
- Sapna Sharma
- Oluf Pedersen
- Ian M. Forgie
Institutions
- University of Geneva (CH)
- University of Copenhagen (DK)
- SIB Swiss Institute of Bioinformatics (CH)
- Centre for Human Genetics (GB)
- University of Ljubljana (SI)
- National University of Singapore (SG)
- University of Eastern Finland (FI)
- University of Dundee (GB)
- Lund University (SE)
- University of Exeter (GB)
- Royal Devon & Exeter NHS Foundation Trust (GB)
- Science for Life Laboratory (SE)
- Novo Nordisk Foundation (DK)
- Ninewells Hospital (GB)
- Gentofte Hospital (DK)
- Helmholtz Zentrum München (DE)
- University of Oxford (GB)
- Oxford Centre for Diabetes, Endocrinology and Metabolism (GB)
- Sanofi (Germany) (DE)
- Genomics (United Kingdom) (GB)
- Deutsches Diabetes-Zentrum e.V. (DE)
- National Research Council (IT)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
- Ludwig-Maximilians-Universität München (DE)
- Newcastle University (GB)
- KTH Royal Institute of Technology (SE)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Diabetologia
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1007/s00125-024-06282-6
- Citations
- 14
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 5.41
Funders
- European Federation of Pharmaceutical Industries and Associations
- European Commission