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Introducción y objetivos La desregulación del metabolismo de los ácidos grasos en la mitocondria es un mecanismo involucrado en el desarrollo de insuficiencia cardiaca (IC) y fibrilación auricular (FA). Se evaluó la asociación entre la concentración plasmática de acilcarnitinas y la incidencia de IC o FA y si la dieta mediterránea (DietMed) puede atenuar la asociación entre las acilcarnitinas y el riesgo de IC o FA. Métodos Dos estudios de casos y controles anidados en el ensayo Prevención con dieta mediterránea (PREDIMED). Se incluyó a participantes con elevado riesgo cardiovascular en España: 326 casos incidentes de IC y 509 de FA se emparejaron individualmente con 1 a 3 controles. Las acilcarnitinas en plasma se midieron con espectrometría de masas en tándem con cromatografía líquida de alta resolución. Se ajustaron modelos de regresión logística condicional para estimar las OR multivariables y los IC95%. Se evaluaron interacciones multiplicativas y aditivas por el grupo de intervención, obesidad (índice de masa corporal ≥ 30) y diabetes mellitus tipo 2. Resultados Las altas concentraciones de acilcarnitinas de cadena mediana y larga se asociaron con un mayor riesgo de IC (respectivamente, ORporDE ajustada=1,28; IC95%, 1,09-1,51, y ORporDE ajustada=1,21; IC95%, 1,04-1,42). Se observó una asociación significativa entre las acilcarnitinas de cadena larga y el riesgo de FA: 1,20 (1,06-1,36). Se encontró una interacción aditiva entre las acilcarnitinas de cadena larga y la FA con la DietMed suplementada con aceite de oliva virgen extra (p de interacción=0,036) y con la obesidad (p=0,022) de forma inversa y directa respectivamente. Conclusiones En las personas con alto riesgo cardiovascular, las altas concentraciones de acilcarnitinas de cadena larga se asocian con mayor riesgo de IC y FA incidentes. Una intervención con DietMed+aceite de oliva virgen extra puede reducir el riesgo asociado con las acilcarnitinas de cadena larga (AU)

Introduction and objectives Fatty acid metabolic dysregulation in mitochondria is a common mechanism involved in the development of heart failure (HF) and atrial fibrillation (AF). We evaluated the association between plasma acylcarnitine levels and the incidence of HF or AF, and whether the mediterranean diet (MedDiet) may attenuate the association between acylcarnitines and HF or AF risk. Methods Two case-control studies nested within the Prevención con dieta mediterránea (PREDIMED) trial. High cardiovascular risk participants were recruited in Spain: 326 incident HF and 509 AF cases individually matched to 1 to 3 controls. Plasma acylcarnitines were measured with high-throughput liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were fitted to estimate multivariable OR and 95%CI. Additive and multiplicative interactions were assessed by intervention group, obesity (body mass index ≥ 30 kg/m2), and type 2 diabetes. Results Elevated levels of medium- and long-chain acylcarnitines were associated with increased HF risk (adjusted ORperDE, 1.28; 95%CI, 1.09-1.51 and adjusted ORperDE, 1.21; 95%CI, 1.04-1.42, respectively). A significant association was observed for AF risk with long-chain acylcarnitines: 1.20 (1.06-1.36). Additive interaction of the association between long-chain acylcarnitines and AF by the MediDiet supplemented with extra virgin olive oil (P for additive interaction=.036) and by obesity (P=.022) was observed in an inverse and direct manner, respectively. Conclusions Among individuals at high cardiovascular risk, elevated long-chain acylcarnitines were associated with a higher risk of incident HF and AF. An intervention with MedDiet+extra-virgin olive oil may reduce AF risk associated with long-chain acylcarnitines (AU)

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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 1H-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. Trial registration at www.controlled-trials.com: ISRCTN35739639.

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