Suchergebnisse

BACKGROUND: Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence of an association between glutamate-related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD). METHODS AND RESULTS: Plasma levels of glutamate and glutamine were measured at baseline and 1-year follow-up in a case-cohort study including 980 participants (mean age 68 years; 46% male) from the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow-up, there were 229 incident CVD events (nonfatal stroke, nonfatal myocardial infarction, or CVD death). In fully adjusted models, per 1-SD, baseline glutamate was associated with 43% (95% CI: 16% to 76%) and 81% (39% to 137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine-to-glutamate ratio with 25% (6% to 40%) and 44% (25% to 58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both Plinear trend≤0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (Pinteraction=0.02). No significant effect of the intervention on year-1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent. CONCLUSIONS: Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine-to-glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels. ; This work was supported by the National Institutes of Health, 1R01HL118264. The PREDIMED trial was supported by the official funding agency for Biomedical Research of the Spanish Government, Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial: RTIC G03/140 (Period 2003–2006, Coordinator: R. Estruch, MD, PhD), and RTIC RD 06/0045 (Period 2007–2013, Coordinator: M. A. Martinez-Gonzalez, MD, PhD). We also acknowledge the grants from Centro Nacional de Investigaciones Cardiovasculares CNIC06/2007,Fondo de Investigaci on Sanitaria—Fondo Europeo de Desarrollo Regional (PI04-2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI08/1259, PI10/01407, PI11/01647, PI11/01791), and Consejer ıa de Salud de la Junta de Andaluc ıa (PI0105/2007). Ministerio de Ciencia e Innovaci on (AGL-2009- 13906-C02, AGL2010-22319-C03), Fundaci on Mapfre 2010, Consejeria de Salud de la Junta de Andalucia (PI0105/2007), Agencia Canaria de Investigaci on, Innovaci on y Sociedad de la Informaci on-EU FEDER (PI 2007/050), Public Health Division of the Department of Health of the Autonomous Government of Catalonia and Generalitat Valenciana (ACOMP06109, GVACOMP2010-181, GVACOMP2011-151, CS2010-AP-111, CS2011-AP-042, AP-042/11 and BEST11-263) and Ministerio de Econom ıa (PI07-0954, CNIC-06, AGL2010-22319-C03-03, PI11/02505). CIBEROBN is an initiative of ISCIII, Spain.

BACKGROUND: The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. METHODS AND RESULTS: We designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N-oxide, betaine, choline, phosphocholine, and α-glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1-SD increase in choline and α-glycerophosphocholine metabolites were 1.24 (1.05-1.46) and 1.24 (1.03-1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21-fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36-3.59; P<0.001 for trend) and a 2.27-fold higher risk of stroke (95% confidence interval, 1.24-4.16; P<0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups (P=0.05 for interaction). No significant associations were observed for 1-year changes in individual plasma metabolites and CVD. CONCLUSIONS: A metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk. ; This work was supported by NIH research grant HL118264. The PREDIMED trial was supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial (RTIC G03/140 to Estruch; RTIC RD 06/0045 to Martínez‐González) and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición; and by grants from Centro Nacional de Investigaciones Cardiovasculares (06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (PI04–2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, and PI13/00462), Ministerio de Ciencia e Innovación (AGL‐2009–13906‐C02 and AGL2010–22319‐C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVA‐COMP2010–181, GVACOMP2011–151, CS2010‐AP‐111, and CS2011‐AP‐042), and Regional Government of Navarra (P27/2011). Guasch‐Ferré was supported by a postdoctoral fellowship granted by the Agency for Administration of University and Research Grants of the Autonomous Government of Catalonia (2014‐BP‐A 00017).

Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated. ; This study was supported by research grant R01-DK-102896 from the National Institutes of Health. The Prevención con DietaMediterránea (PREDIMED) trial was supported by the official funding agency for biomedical research of the Spanish government, the Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial [grant RTIC G03/140 (to Ramón Estruch); grant RTIC RD 06/0045 (to Miguel A. Martínez-González)] and through the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición and by grants from Centro Nacional de Investigaciones Cardiovasculares (grant CNIC 06/2007), the Fondo de Investigación Sanitaria Fondo Europeo de Desarrollo Regional (grants PI04–2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, and PI13/00462), the Ministerio de Ciencia e Innovación (grants AGL-2009–13906-C02 and AGL2010–22319-C03), the Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (grant PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (grants ACOMP06109, GVA-COMP2010–181, GVACOMP2011–151, CS2010-AP-111, and CS2011-AP-042), and the Regional Government of Navarra (grant P27/2011). Genotyping of the TCF7L2-rs7903146 polymorphism was supported by PROMETEO17/2017 from the Generalitat Valenciana, and 538/U/2016 from Fundacio la Marato-TV3. Dr. Christopher Papandreou was supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS 2016-2020 INCORPORACIÓ DE CIENTÍFICAS I TECNÒLEGS, SLT002/0016/00428). Dr Marta Guasch-Ferré was supported by a postdoctoral fellowship granted by the Lilly Foundation European Association of Diabetes (EASD) through the Institut d'Investigacions Sanitàries Pere i Virgili (IISPV), Tarragona, Spain. The authors are indebted to George A. Fragkiadakis (Department of Nutrition & Dietetics, Technological Education Institute of Crete, Greece) for his intellectual contributions to this manuscript.

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56–0.64), 0.78 (95% CI 0.75–0.81) and 0.52 (95% CI 0.49–0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption. ; This study was funded by the National Institutes of Health (R01DK102896, F31DK114938, NIH/NHLBI 1R01HL118264, NIH/NHLBI 2R01HL118264), the Spanish Ministry of Health (Instituto de Salud Carlos III, RD 06/0045- Coordinator: MAM-G), the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, RTIC G03/140, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304 and AGL2010-22319-C03-03), and by the Generalitat Valenciana (ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159 and ACOMP/213/165). Dr. Christopher Papandreou was supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS2016-2020 Incorporació de Científics I Tecnòlegs, SLT002/0016/00428). Dr. Marta Guasch-Ferré was supported by EFSD (European Foundation for the Study of Diabetes)/Lilly through the Institut d'Investigacions Sanitàries Pere I Virgili (IISPV).