Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population

Abstract Introduction Prediabetes and preclinical atherosclerosis are interrelated conditions contributing to cardiovascular risk, even in apparently healthy individuals. Metabolomics provides insights into the early metabolic alterations underpinning these diseases. Objectives This study aimed to i...

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Main Authors: Natalia Zieleniewska, Jacek Jamiołkowski, Marcin Kondraciuk, Michal Ciborowski, Katarzyna Ptaszyńska, Małgorzata Chlabicz, Marlena Dubatówka, Urszula Roszkowska, Irina Kowalska, Karol Kamiński
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cardiovascular Diabetology
Online Access:https://doi.org/10.1186/s12933-025-02841-2
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author Natalia Zieleniewska
Jacek Jamiołkowski
Marcin Kondraciuk
Michal Ciborowski
Katarzyna Ptaszyńska
Małgorzata Chlabicz
Marlena Dubatówka
Urszula Roszkowska
Irina Kowalska
Karol Kamiński
author_facet Natalia Zieleniewska
Jacek Jamiołkowski
Marcin Kondraciuk
Michal Ciborowski
Katarzyna Ptaszyńska
Małgorzata Chlabicz
Marlena Dubatówka
Urszula Roszkowska
Irina Kowalska
Karol Kamiński
author_sort Natalia Zieleniewska
collection DOAJ
description Abstract Introduction Prediabetes and preclinical atherosclerosis are interrelated conditions contributing to cardiovascular risk, even in apparently healthy individuals. Metabolomics provides insights into the early metabolic alterations underpinning these diseases. Objectives This study aimed to investigate the shared and distinct metabolic signatures associated with prediabetes and preclinical atherosclerosis in a population with low to moderate cardiovascular risk, using a targeted metabolomic approach. Methods A cross-sectional analysis was performed on 447 participants (mean age 39.7 ± 9.6 years) from the Białystok PLUS cohort. Prediabetes was diagnosed based on HbA1c and OGTT criteria. Preclinical atherosclerosis was assessed by carotid ultrasound. Targeted metabolomics profiling encompassed 434 metabolites and 218 metabolite sums or ratios using HPLC–MS/MS. Statistical analyses included ANOVA, linear regression, correlation analysis, and metabolite set enrichment analysis (MSEA). Results Prediabetes was significantly associated with preclinical atherosclerosis (30.8% vs. 19.5%, p = 0.006). Prediabetes had a broader metabolic impact than atherosclerosis, particularly affecting amino acid and lipid metabolism. Glutamic acid, lactic acid, and L-alanine were strongly associated with prediabetes. Trimethylamine N-oxide (TMAO) was uniquely linked to both prediabetes and its interaction with atherosclerosis, suggesting a context-dependent metabolic response. Glutaminase activity emerged as a robust shared metabolic feature of both conditions. Pathway analyses revealed converging disturbances in glutathione and folate metabolism, mitochondrial function, and redox regulation. Conclusions Prediabetes is associated with more pronounced metabolic alterations than preclinical atherosclerosis. TMAO and glutaminase activity may represent key metabolic links between these conditions. These findings highlight the potential of metabolomics in identifying early biomarkers and mechanisms relevant to the prevention of cardiometabolic diseases.
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spelling doaj-art-1f5cf6a29c674dbc94b453f88e72239d2025-08-20T03:45:44ZengBMCCardiovascular Diabetology1475-28402025-07-0124111510.1186/s12933-025-02841-2Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy populationNatalia Zieleniewska0Jacek Jamiołkowski1Marcin Kondraciuk2Michal Ciborowski3Katarzyna Ptaszyńska4Małgorzata Chlabicz5Marlena Dubatówka6Urszula Roszkowska7Irina Kowalska8Karol Kamiński9Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of BialystokDepartment of Population Medicine and Lifestyle Diseases Prevention, Medical University of BialystokDepartment of Population Medicine and Lifestyle Diseases Prevention, Medical University of BialystokMetabolomics Laboratory, Clinical Research Centre, Medical University of BialystokDepartment of Cardiology and Internal Medicine, University Hospital of BialystokDepartment of Population Medicine and Lifestyle Diseases Prevention, Medical University of BialystokDepartment of Population Medicine and Lifestyle Diseases Prevention, Medical University of BialystokDepartment of Population Medicine and Lifestyle Diseases Prevention, Medical University of BialystokDepartment of Internal Medicine and Metabolic Diseases, Medical University of BialystokDepartment of Population Medicine and Lifestyle Diseases Prevention, Medical University of BialystokAbstract Introduction Prediabetes and preclinical atherosclerosis are interrelated conditions contributing to cardiovascular risk, even in apparently healthy individuals. Metabolomics provides insights into the early metabolic alterations underpinning these diseases. Objectives This study aimed to investigate the shared and distinct metabolic signatures associated with prediabetes and preclinical atherosclerosis in a population with low to moderate cardiovascular risk, using a targeted metabolomic approach. Methods A cross-sectional analysis was performed on 447 participants (mean age 39.7 ± 9.6 years) from the Białystok PLUS cohort. Prediabetes was diagnosed based on HbA1c and OGTT criteria. Preclinical atherosclerosis was assessed by carotid ultrasound. Targeted metabolomics profiling encompassed 434 metabolites and 218 metabolite sums or ratios using HPLC–MS/MS. Statistical analyses included ANOVA, linear regression, correlation analysis, and metabolite set enrichment analysis (MSEA). Results Prediabetes was significantly associated with preclinical atherosclerosis (30.8% vs. 19.5%, p = 0.006). Prediabetes had a broader metabolic impact than atherosclerosis, particularly affecting amino acid and lipid metabolism. Glutamic acid, lactic acid, and L-alanine were strongly associated with prediabetes. Trimethylamine N-oxide (TMAO) was uniquely linked to both prediabetes and its interaction with atherosclerosis, suggesting a context-dependent metabolic response. Glutaminase activity emerged as a robust shared metabolic feature of both conditions. Pathway analyses revealed converging disturbances in glutathione and folate metabolism, mitochondrial function, and redox regulation. Conclusions Prediabetes is associated with more pronounced metabolic alterations than preclinical atherosclerosis. TMAO and glutaminase activity may represent key metabolic links between these conditions. These findings highlight the potential of metabolomics in identifying early biomarkers and mechanisms relevant to the prevention of cardiometabolic diseases.https://doi.org/10.1186/s12933-025-02841-2
spellingShingle Natalia Zieleniewska
Jacek Jamiołkowski
Marcin Kondraciuk
Michal Ciborowski
Katarzyna Ptaszyńska
Małgorzata Chlabicz
Marlena Dubatówka
Urszula Roszkowska
Irina Kowalska
Karol Kamiński
Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population
Cardiovascular Diabetology
title Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population
title_full Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population
title_fullStr Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population
title_full_unstemmed Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population
title_short Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population
title_sort preclinical atherosclerosis and prediabetes a cross sectional metabolic assessment in apparently healthy population
url https://doi.org/10.1186/s12933-025-02841-2
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