Evidence mapPaperPMID 41444601Full record

ArticleCardiovascular diabetology2025

Improved sex-specific cardiovascular risk prediction with multi-omics data in people with type 2 diabetes.

Ruijie Xie, Christian Herder, Sha Sha, Hermann Brenner, Sigrid Carlsson, Ben Schöttker

Abstract readComparative Study
In one paragraph

Article in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Ruijie XieDivision of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Christian HerderInstitute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Sha ShaDivision of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Hermann BrennerDivision of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Sigrid CarlssonDivision of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Ben SchöttkerDivision of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. b.schoettker@dkfz.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo evaluate whether integrating proteomics, metabolomics, and a cardiovascular disease specific polygenic risk score (CVD-PRS) in the SCORE2-Diabetes model improves sex-specific 10-year prediction of major adverse cardiovascular events (MACE) in individuals with type 2 diabetes (T2D).

methodsGenome-wide association study (GWAS), plasma proteomics (with the Olink Explore 3072 platform), and metabolomics (with nuclear magnetic resonance spectroscopy by Nightingale Health) data were measured in the UK Biobank. A novel sex-specific protein algorithm was developed using bootstrap-LASSO (Least absolute shrinkage and selection operator) regression. The CVD-PRS and sex-specific metabolite algorithms were used from previous UK Biobank projects. In a subset of 990 participants with T2D, age 40-69 years, with no prior MACE, and complete multi-omics data, we evaluated, which omics data improved the SCORE2-Diabetes model performance using Harrell's C-index.

resultsOverall 9 proteins were selected for males and 7 for females and adding them to the SCORE2-Diabetes model significantly improved discrimination in the total population (C-index increase from 0.766 to 0.835 (P < 0.001)). Further adding of metabolites significantly improved model performance (C-index, 0.846, P = 0.035), which was mostly attributable to model improvement among males (∆C-index, 0.012, P = 0.078) but not among females (∆C-index, 0.004, P = 0.723). Further adding the CVD-PRS did not statistically significantly improve the SCORE2-Diabetes + proteomics + metabolomics model further in the total population (C-index, 0.848 (P = 0.070)).

conclusionsSex-specific proteomic signatures markedly improved 10-year MACE risk prediction in individuals with T2D. In men but not in women, further integration of metabolomics may enhance model performance whereas adding the CVD-PRS is not needed. External validation is warranted.

Indexed as

Cardiovascular DiseasesDecision Support TechniquesDiabetes Mellitus, Type 2MetabolomicsProteomicsAdultAgedBiomarkersFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHeart Disease Risk FactorsHumansMaleMiddle AgedMultiomicsBiomarkersCardiovascular riskMulti-omicsProteomicsSCORE2-diabetesSex-specificType 2 diabetes

Identifiers

PMID41444601
PMCPMC12837037

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.