Cardiovascular Diabetology (Nov 2019)

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

  • Cristina Razquin,
  • Miguel Ruiz-Canela,
  • Clary B. Clish,
  • Jun Li,
  • Estefania Toledo,
  • Courtney Dennis,
  • Liming Liang,
  • Albert Salas-Huetos,
  • Kerry A. Pierce,
  • Marta Guasch-Ferré,
  • Dolores Corella,
  • Emilio Ros,
  • Ramon Estruch,
  • Enrique Gómez-Gracia,
  • Montse Fitó,
  • Jose Lapetra,
  • Dora Romaguera,
  • Angel Alonso-Gómez,
  • Lluis Serra-Majem,
  • Jordi Salas-Salvadó,
  • Frank B. Hu,
  • Miguel A. Martínez-González

DOI
https://doi.org/10.1186/s12933-019-0958-2
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 12

Abstract

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Abstract 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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