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Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants
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Aim. - To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. Methods. - A metabolomics analysis using the 1 H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm. Results. - A total of 33 metabolites were significantly different (P < 0.05) between T2D and non-T2D participants. The multi-metabolite signature of T2D comprised high levels of methylsuccinate, alanine, dimethylglycine and guanidoacetate, and reduced levels of glutamine, methylguanidine, 3-hydroxymandelate and hippurate, and had a 96.4% AUC, which was higher than the metabolites on their own and glucose. Amino-acid and carbohydrate metabolism were the main metabolic alterations in T2D, and various metabotypes were identified in the studied population. Among T2D participants, those with a metabotype of higher levels of phenylalanine, phenylacetylglutamine, p-cresol and acetoacetate had significantly higher levels of plasma glucose. Conclusion. - The multi-metabolite signature of T2D highlights the altered metabolic fingerprint associated mainly with amino-acid, carbohydrate and microbiota metabolism. Metabotypes identified in this patient population could be related to higher risk of long-term cardiovascular events and therefore require further studies. Metabolomics is a useful tool for elucidating the metabolic complexity and interindividual variation in T2D towards the development of stratified precision nutrition and medicine
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URPÍ SARDÀ, Mireia, ALMANZA AGUILERA, Enrique, LLORACH, Rafael, VÁZQUEZ FRESNO, Rosa, ESTRUCH RIBA, Ramon, CORELLA PIQUER, Dolores, SORLÍ, José v., CARMONA PONTAQUE, Francesc, SÀNCHEZ, Àlex (sànchez pla), SALAS SALVADÓ, Jordi, ANDRÉS LACUEVA, Ma. cristina. Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants. _Diabetes & Metabolism_. 2019. Vol. 45, núm. 2, pàgs. 167-174. [consulta: 21 de gener de 2026]. ISSN: 1262-3636. [Disponible a: https://hdl.handle.net/2445/163513]