Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics

Background: Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MA...

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Hauptverfasser: Xie, Ruijie (VerfasserIn) , Seum, Teresa (VerfasserIn) , Sha, Sha (VerfasserIn) , Trares, Kira (VerfasserIn) , Holleczek, Bernd (VerfasserIn) , Brenner, Hermann (VerfasserIn) , Schöttker, Ben (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 13 January 2025
In: Cardiovascular diabetology
Year: 2025, Jahrgang: 24, Pages: 1-12
ISSN:1475-2840
DOI:10.1186/s12933-025-02581-3
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s12933-025-02581-3
Verlag, kostenfrei, Volltext: https://cardiab.biomedcentral.com/articles/10.1186/s12933-025-02581-3
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Verfasserangaben:Ruijie Xie, Teresa Seum, Sha Sha, Kira Trares, Bernd Holleczek, Hermann Brenner and Ben Schöttker

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520 |a Background: Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients. Methods: Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. Sex-specific LASSO regression with bootstrapping identified significant metabolites. The enhanced model’s predictive performance was evaluated using Harrell’s C-index. Results: Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P = 0.037) from 0.660 to 0.678 in the total sample. In external validation with ESTHER, the C-index increase was higher (+ 0.043) and remained statistically significant (P = 0.011). Conclusions: Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine. 
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