Zieleniewska Natalia, Jamiołkowski Jacek, Kondraciuk Marcin, Ciborowski Michal, Ptaszyńska Katarzyna, Chlabicz Małgorzata, Dubatówka Marlena, Roszkowska Urszula, Kowalska Irina, Kamiński Karol
Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Białystok, Poland.
Department of Cardiology and Internal Medicine, University Hospital of Bialystok, Białystok, Poland.
Cardiovasc Diabetol. 2025 Jul 10;24(1):280. doi: 10.1186/s12933-025-02841-2.
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.
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.
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).
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.
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.
即使在看似健康的个体中，糖尿病前期和临床前动脉粥样硬化也是相互关联的状况，会增加心血管疾病风险。代谢组学有助于深入了解这些疾病背后的早期代谢变化。
本研究旨在采用靶向代谢组学方法，调查心血管疾病风险较低至中等的人群中与糖尿病前期和临床前动脉粥样硬化相关的共同和独特代谢特征。
对来自比亚韦斯托克PLUS队列的447名参与者（平均年龄39.7±9.6岁）进行横断面分析。根据糖化血红蛋白（HbA1c）和口服葡萄糖耐量试验（OGTT）标准诊断糖尿病前期。通过颈动脉超声评估临床前动脉粥样硬化。靶向代谢组学分析使用高效液相色谱-串联质谱法（HPLC-MS/MS）涵盖434种代谢物以及218种代谢物总和或比率。统计分析包括方差分析（ANOVA）、线性回归、相关性分析和代谢物集富集分析（MSEA）。
糖尿病前期与临床前动脉粥样硬化显著相关（30.8%对19.5%，p = 0.006）。糖尿病前期比动脉粥样硬化具有更广泛的代谢影响，尤其影响氨基酸和脂质代谢。谷氨酸、乳酸和L-丙氨酸与糖尿病前期密切相关。氧化三甲胺（TMAO）与糖尿病前期及其与动脉粥样硬化的相互作用独特相关，表明存在依赖于背景的代谢反应。谷氨酰胺酶活性是这两种状况共同的强大代谢特征。通路分析揭示了谷胱甘肽和叶酸代谢、线粒体功能和氧化还原调节方面的共同紊乱。
糖尿病前期比临床前动脉粥样硬化伴有更明显的代谢改变。TMAO和谷氨酰胺酶活性可能是这些状况之间关键的代谢联系。这些发现突出了代谢组学在识别与预防心脏代谢疾病相关的早期生物标志物和机制方面的潜力。
