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1. Anti-Inflammatory Effects of the Mediterranean Diet in the Early and Late Stages of Atheroma Plaque Development

Author

Jordi Salas-Salvadó, María P. Portillo, Olga Castañer, Sara Arranz, Rosa Casas, Dolores Corella, Mireia Urpi-Sarda, R. M. Lamuela-Raventos, Emilio Sacanella, Ramon Estruch, José Lapetra, [Casas, Rosa] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Villarroel 170, E-08036 Barcelona, Spain, [Sacanella, Emilio] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Villarroel 170, E-08036 Barcelona, Spain, [Arranz, Sara] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Villarroel 170, E-08036 Barcelona, Spain, [Estruch, Ramon] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Villarroel 170, E-08036 Barcelona, Spain, [Casas, Rosa] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Sacanella, Emilio] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Arranz, Sara] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Corella, Dolores] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Castaner, Olga] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Lamuela-Raventos, Rosa-Maria] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Salas-Salvado, Jordi] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Lapetra, Jose] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Portillo, Maria P.] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Estruch, Ramon] Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain, [Urpi-Sarda, Mireia] Univ Barcelona, Sch Pharm, Dept Nutr & Food Sci, Av Joan XXIII S-N, E-08028 Barcelona, Spain, [Lamuela-Raventos, Rosa-Maria] Univ Barcelona, Sch Pharm, Dept Nutr & Food Sci, Av Joan XXIII S-N, E-08028 Barcelona, Spain, [Corella, Dolores] Univ Valencia, Sch Med, Dept Epidemiol, Valencia, Spain, [Corella, Dolores] Univ Valencia, Sch Med, Dept Biochem & Mol Biol, Valencia, Spain, [Castaner, Olga] Hosp Mar Med Res Inst IMIM, Cardiovasc Risk & Nutr & REGICOR Res Grp, Barcelona, Spain, [Salas-Salvado, Jordi] Univ Rovira & Virgili, Hosp Univ Sant Joan Reus, IISPV, Human Nutr Unit, Reus, Spain, [Lapetra, Jose] Distrito Sanitario Atenc Primaria Sevilla, Dept Family Med, Res Unit, Seville, Spain, [Portillo, Maria P.] Univ Basque Country, UPV EHU, Lucio Lascaray Res Ctr, Dept Nutr & Food Sci,Nutr & Obes Grp, Vitoria, Spain, Instituto de Salud Carlos III, Spain, 'Ramon y Cajal' program of MINECO, Fondo Social Europeo, Universitat de Barcelona, Alimentació, Nutrició, Creixement i Salut Mental, Bioquímica i Biotecnologia, and Universitat Rovira i Virgili

Subjects
Male, 0301 basic medicine, Pathology, Mediterranean diet, High-risk, 030204 cardiovascular system & hematology, Diet, Mediterranean, Dieta mediterrània, Gastroenterology, 0302 clinical medicine, Risk Factors, Elderly people, Chemokine CCL4, Chemokine CCL5, Diet, Fat-Restricted, Aged, 80 and over, Bioquímica y tecnología, Interleukin-18, Middle Aged, Inflammatory biomarkers, Plaque, Atherosclerotic, Interleukin-10, Lipoproteins, LDL, Biochemistry and technology, Cardiovascular diseases, Cardiovascular Diseases, Plasma concentration, Cytokines, Female, lcsh:RB1-214, medicine.medical_specialty, Article Subject, medicine.drug_class, Immunology, Vascular Cell Adhesion Molecule-1, Activation, Primary care, Bioquímica i biotecnologia, Low-grade inflammation, Anti-inflammatory, 03 medical and health sciences, Mediterranean cooking, Elderly persons, Cardiovascular-disease, Internal medicine, Cuina mediterrània, lcsh:Pathology, medicine, Humans, Aged, Markers, 030109 nutrition & dietetics, Interleukin-6, Malalties cardiovasculars, business.industry, Pattern, Cell Biology, medicine.disease, Atherosclerosis, Atheroma, Clinical Study, 0962-9351, Placa ateroscleròtica, business
Abstract

Objective.To evaluate the long-term effects of a Mediterranean diet (MeDiet) intervention on the plasma concentrations of inflammatory and plaque stability-related molecules in elderly people at high risk for cardiovascular disease.Design and Setting. 66 participants from primary care centers affiliated with the Hospital Clinic of Barcelona were randomized into 3 groups: MeDiet plus extra virgin olive oil (EVOO) or nuts and a low-fat diet (LFD). At baseline and at 3 and 5 years, we evaluated the changes in the plasma concentrations of 24 inflammatory biomarkers related to the different stages of the atherosclerotic process by Luminex®.Results.At 3 and 5 years, both MeDiet groups showed a significant reduction of IL-6, IL-8, MCP-1, and MIP-1β(P<0.05; all) compared to LFD. IL-1β, IL-5, IL-7, IL-12p70, IL-18, TNF-α, IFN-γ, GCSF, GMCSF, and ENA78 (P<0.05; all) only decreased in the MeDiet+EVOO group and E-selectin and sVCAM-1 (P<0.05; both) in the MeDiet+nuts group.Conclusions. Long-term adherence to MeDiet decreases the plasma concentrations of inflammatory biomarkers related to different steps of atheroma plaque development in elderly persons at high cardiovascular risk.

Published
2017
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2. Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores

Author

Laura Quiles, José V. Sorlí, Miquel Fiol, Fernando Arós, Manuel Ortega-Calvo, Jordi Salas-Salvadó, Josep Basora, Ramon Estruch, Emilio Ros, Olga Portolés, Oscar Coltell, Dolores Corella, Miguel Ángel Martínez-González, Montserrat Fitó, Olga Castañer, Lluis Serra-Majem, Javier Díez Espino, Jose M. Ordovas, Enrique Gómez-Gracia, [Corella, Dolores] Univ Valencia, Sch Med, Dept Prevent Med & Publ Hlth, Valencia 46010, Spain, [Sorli, Jose V.] Univ Valencia, Sch Med, Dept Prevent Med & Publ Hlth, Valencia 46010, Spain, [Quiles, Laura] Univ Valencia, Sch Med, Dept Prevent Med & Publ Hlth, Valencia 46010, Spain, [Portoles, Olga] Univ Valencia, Sch Med, Dept Prevent Med & Publ Hlth, Valencia 46010, Spain, [Corella, Dolores] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Coltell, Oscar] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Sorli, Jose V.] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Estruch, Ramon] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Quiles, Laura] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Angel Martinez-Gonzalez, Miguel] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Salas-Salvado, Jordi] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Castaner, Olga] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Aros, Fernando] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Ortega-Calvo, Manuel] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Serra-Majem, Lluis] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Gomez-Gracia, Enrique] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Portoles, Olga] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Fiol, Miquel] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Diez Espino, Javier] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Basora, Josep] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Fito, Montserrat] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Ros, Emilio] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Ordovas, Jose M.] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid 28029, Spain, [Coltell, Oscar] Univ Jaume 1, Dept Comp Languages & Syst, Sch Technol & Expt Sci, Castellon de La Plana 12071, Spain, [Estruch, Ramon] IDIBAPS, Hosp Clin, Dept Internal Med, Barcelona 08036, Spain, [Angel Martinez-Gonzalez, Miguel] Univ Navarra, Dept Prevent Med & Publ Hlth, Navarra Inst Hlth Res IdisNa, Pamplona 31009, Spain, [Salas-Salvado, Jordi] Univ Rovira & Virgili, Human Nutr Unit, Dept Biochem & Biotechnol, IISPV, Reus 43003, Spain, [Basora, Josep] Univ Rovira & Virgili, Human Nutr Unit, Dept Biochem & Biotechnol, IISPV, Reus 43003, Spain, [Castaner, Olga] Hosp del Mar Med Res Inst IMIM, Cardiovasc Risk & Nutr Res Grp, Barcelona 08003, Spain, [Fito, Montserrat] Hosp del Mar Med Res Inst IMIM, Cardiovasc Risk & Nutr Res Grp, Barcelona 08003, Spain, [Aros, Fernando] Hosp Txagorritxu, Dept Cardiol, Vitoria 01009, Spain, [Ortega-Calvo, Manuel] Ctr Salud Palmeritas, Dept Family Med, Dist Sanitario Atenc Primaria Sevilla, Seville 41003, Spain, [Serra-Majem, Lluis] Univ Las Palmas Gran Canaria, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria 35001, Spain, [Gomez-Gracia, Enrique] Univ Malaga, Sch Med, Dept Epidemiol, E-29071 Malaga, Spain, [Fiol, Miquel] Hosp Son Espases, Palma Inst Hlth Res IdISPa, Palma De Mallorca 07014, Spain, [Diez Espino, Javier] Univ Navarra, Dept Prevent Med & Publ Hlth, Navarra Inst Hlth Res IdisNA, Serv Navarro Salud Osasunbidea, Pamplona 31009, Spain, [Ros, Emilio] Hosp Clin Barcelona, Inst Invest Biomed August Pi Sunyer IDIBAPS, Lipid Clin, Endocrinol & Nutr Serv, E-08036 Barcelona, Spain, [Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA, [Ordovas, Jose M.] CNIC, Dept Cardiovasc Epidemiol & Populat Genet, Madrid 28029, Spain, [Ordovas, Jose M.] IMDEA Alimentac, Madrid 28049, Spain, Spanish Ministry of Health (Instituto de Salud Carlos III), Ministerio de Economia y Competitividad-Fondo Europeo de Desarrollo Regional, University Jaume I, Generalitat Valenciana, FEDER funds, U.S. Department of Agriculture-Agricultural Research Service (ARS), Alimentació, Nutrició, Creixement i Salut Mental, Departament de Medicina i Cirurgia, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Jaume I University (España), Generalitat Valenciana (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), and United States Department of Agriculture. Agricultural Research Service

Subjects
0301 basic medicine, Oncology, Male, obesity, endocrine system diseases, Type 2 diabetes, type-2 diabetes, Transcription Factor 7-Like 2, Dieta mediterrània, 0302 clinical medicine, Nutrigenomics, Risk Factors, Prevalence, TCF7L2-predictive value, Disease, Longitudinal Studies, Prospective Studies, Genetic risk, Genetics, Aged, 80 and over, INSULIN-RESISTANCE, Bioquímica y tecnología, Nutrition and Dietetics, Diabetis, Incidence, Middle Aged, Traits, MEDITERRANEAN DIET, Biochemistry and technology, Obesitat, TRIAL, Female, lcsh:Nutrition. Foods and food supply, Transcription Factor 7-Like 2 Protein, Adult, Genetic Markers, medicine.medical_specialty, endocrine system, Population, BODY-FAT, lcsh:TX341-641, 030209 endocrinology & metabolism, MASS, Bioquímica i biotecnologia, Article, Association, 03 medical and health sciences, Genetic Heterogeneity, Predictive Value of Tests, Internal medicine, Diabetes mellitus, medicine, Humans, Genetic Predisposition to Disease, Gene, Aged, Polymorphism, Genetic, business.industry, Common variants, Prevention, nutritional and metabolic diseases, Genetic Variation, PREDIMED study, medicine.disease, 2072-6643, Weight, Predimed, Obesity, TCF7L2, T2D-genetic risk scores, 030104 developmental biology, Diabetes Mellitus, Type 2, Susceptibility loci, business, Food Science
Abstract

Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects (n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13-2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61-1.66; p = 0.979; p-interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D., This study was funded by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economia y Competitividad-Fondo Europeo de Desarrollo Regional (projects PI051839, PI070240, PI1001407, G03/140, CIBER 06/03, RD06/0045 PI07-0954, CNIC-06, PI11/02505, SAF2009-12304, AGL2010-22319-C03-03, and PRX14/00527; contract JR14/00008), by the University Jaume I (Project P1-1B2013-54) and by the Generalitat Valenciana (AP111/10, AP-042/11, BEST/2015/087, GVACOMP2011-151, ACOMP/2011/145, ACOMP/2012/190, and ACOMP/2013/159). CIBEROBN is an initiative of Institute of Health Carlos III of Spain which is supported by FEDER funds (CB06/03). This material is based upon work supported by the U.S. Department of Agriculture-Agricultural Research Service (ARS), under Agreement No. 58-1950-4-003. Dolores Corella acknowledges the collaboration of the Real Colegio Complutense at Harvard University, Cambridge. MA, USA. The PREDIMED study was registered at controlled-trials.com (http://www.controlledtrials.com/ISRCTN35739639; ethics approval by the Institutional Review Board of the Hospital Clinic at Barcelona, Spain, 16/07/2002, under the protocol number G03/140). The Institutional Review Board of each participating center approved the study protocol, and all participants provided written informed consent. The Institutional Review Board of the Valencia University (protocol number G03/140, 22/05/2003) approved the PREDIMED-Valencia study protocol, and all participants provided written informed consent.

Published
2016

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