Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies

BACKGROUND: The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic aci...

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Detalles Bibliográficos
Autores principales: Razquin, Cristina, Ruiz-Canela, Miguel, Clish, Clary B., Li, Jun, Toledo, Estefania, Dennis, Courtney, Liang, Liming, Salas-Huetos, Albert, Pierce, Kerry A., Guasch-Ferré, Marta, Corella, Dolores, Ros, Emilio, Estruch, Ramon, Gómez-Gracia, Enrique, Fitó, Montse, Lapetra, Jose, Romaguera, Dora, Alonso-Gómez, Angel, Serra-Majem, Lluis, Salas-Salvadó, Jordi, Hu, Frank B., Martínez-González, Miguel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Original Investigation
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852717/
https://www.ncbi.nlm.nih.gov/pubmed/31722714
http://dx.doi.org/10.1186/s12933-019-0958-2
Descripción
Sumario:BACKGROUND: The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk. METHODS: Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography–tandem mass spectrometry, at baseline and after 1-year of intervention. RESULTS: In weighted Cox regression models, we found that baseline lysine (HR(+1 SD increase) = 1.26; 95% CI 1.06–1.51) and 2-AAA (HR(+1 SD increase) = 1.28; 95% CI 1.05–1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites. CONCLUSIONS: Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found. Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003

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