Pierce, K.A. (Kerry A.)

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    Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies
    (Springer Science and Business Media LLC, 2019) Martinez-Gonzalez, M.A. (Miguel Ángel); Clish, C.B. (Clary B.); Salas-Huetos, A. (Albert); Pierce, K.A. (Kerry A.); Fito, M. (Montserrat); Hu, F.B. (Frank B.); Li, J. (Jun); Gomez-Gracia, E. (Enrique); Toledo, E. (Estefanía); Romaguera, D. (Dora); Lapetra, J. (José); Guasch-Ferre, M. (Marta); Razquin, C. (Cristina); Liang, L. (Liming); Ros, E. (Emilio); Ruiz-Canela, M. (Miguel); Alonso-Gomez, A. (Ángel); Dennis, C. (Courtney); Estruch, R. (Ramón); Serra-Majem, L. (Luis); Corella, D. (Dolores); Salas-Salvado, J. (Jordi)
    Background: The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identifcation of new predictor biomarkers. Biomarkers potentially modifable 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 efect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the efects of these metabolites on CVD or T2D risk. Methods: Two unstratifed 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 quantifed 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 signifcant 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 signifcant efect 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 efects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found.