TY - JOUR

T1 - Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study

T2 - results from two case-cohort studies

AU - Razquin, Cristina

AU - Ruiz-Canela, Miguel

AU - Clish, Clary B

AU - Li, Jun

AU - Toledo, Estefania

AU - Dennis, Courtney

AU - Liang, Liming

AU - Salas-Huetos, Albert

AU - Pierce, Kerry A

AU - Guasch-Ferré, Marta

AU - Corella, Dolores

AU - Ros, Emilio

AU - Estruch, Ramon

AU - Gómez-Gracia, Enrique

AU - Fitó, Montse

AU - Lapetra, Jose

AU - Romaguera, Dora

AU - Alonso-Gómez, Angel

AU - Serra-Majem, Lluis

AU - Salas-Salvadó, Jordi

AU - Hu, Frank B

AU - Martínez-González, Miguel A

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - 2-Aminoadipic Acid/blood

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers/blood

KW - Cardiovascular Diseases/blood

KW - Diabetes Mellitus, Type 2/blood

KW - Diet, Mediterranean

KW - Female

KW - Humans

KW - Incidence

KW - Lysine/blood

KW - Male

KW - Middle Aged

KW - Pipecolic Acids/blood

KW - Primary Prevention

KW - Prospective Studies

KW - Randomized Controlled Trials as Topic

KW - Risk Assessment

KW - Risk Factors

KW - Risk Reduction Behavior

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1186/s12933-019-0958-2

DO - 10.1186/s12933-019-0958-2

M3 - Journal article

C2 - 31722714

VL - 18

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

SN - 1475-2840

M1 - 151

ER -