ArticleResearch square2025
Metabolomic Signatures in Adults with Metabolic Syndrome Indicate Preclinical Disruptions in Pathways Associated with High-Density Lipoprotein Cholesterol, Sugar Alcohols.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Metabolic syndrome is a pressing public health issue and risk factor for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD), yet clinical practice is lacking in biomarkers that represent pre-clinical perturbations of the heterogenous subtypes of risk. This study aimed to characterize the baseline metabolome in relation to known clinical characteristics of risk in a sample of obese adults. Methods: Untargeted metabolome data from Results: The sample consisted primarily of female (74%) participants, predominantly white (70%), with an average age of 56 years. After FDR adjustment, two baseline metabolites were significantly associated with age (xylose, threitol), two with BMI (shikimic acid, propane-1,3-diol), one with LDL (tocopherol-alpha), and 42 with HDL cholesterol. Three metabolites were significantly associated with fasting blood glucose (FBG) levels at baseline (glucose, gluconic acid lactone, pelargonic acid). Conclusions: This study identified novel metabolite associations with known markers of T2D and CVD risk. Specific metabolites, such as alpha-tocopherol, branched-chain amino acids (BCAAs), and sugar-derived metabolites like mannose and xylose, were significantly associated with age, BMI, lipid profiles, and glucose measures. Although most sample participants had normal HDL cholesterol at baseline, 42 metabolites including branched chain amino acids were significantly associated with HDL, suggesting pre-clinical perturbations in biological pathways associated with both diabetes and cardiovascular comorbidities. Metabolomic signatures Specific to prediabetes and metabolic syndrome can enhance risk stratification and enable targeted prevention strategies for T2D. Longitudinal studies are needed to understand how these associations change over time in at-risk individuals compared with controls.
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