Modulation of circulating levels of advanced glycation end products and its impact on intima-media thickness of both common carotid arteries: CORDIOPREV randomised controlled trial.


Journal

Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637

Informations de publication

Date de publication:
14 Oct 2024
Historique:
received: 21 07 2024
accepted: 21 09 2024
medline: 15 10 2024
pubmed: 15 10 2024
entrez: 14 10 2024
Statut: epublish

Résumé

Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD). 1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal-MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention. The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p < 0.001). The Mediterranean diet, but not the low-fat diet, produced an upregulation of AGE metabolism, with increased AGER1 and GloxI gene expression as well as increased GSH and sRAGE levels in Non-increased IMT-CC patients (all p < 0.05). Although the Mediterranean diet increased MG levels in Increased IMT-CC patients, this increment was lower compared to the low-fat diet (all p < 0.05). Our results suggest that an improvement in modulation of AGE metabolism, which facilitates better management of circulating AGE levels, may be one of the mechanisms through which the Mediterranean diet, compared to a low-fat diet, reduces the progression of atherosclerosis in patients with CHD. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 , Clinicaltrials.gov number, NCT00924937.

Sections du résumé

BACKGROUND BACKGROUND
Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD).
METHODS METHODS
1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal-MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention.
RESULTS RESULTS
The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p < 0.001). The Mediterranean diet, but not the low-fat diet, produced an upregulation of AGE metabolism, with increased AGER1 and GloxI gene expression as well as increased GSH and sRAGE levels in Non-increased IMT-CC patients (all p < 0.05). Although the Mediterranean diet increased MG levels in Increased IMT-CC patients, this increment was lower compared to the low-fat diet (all p < 0.05).
CONCLUSIONS CONCLUSIONS
Our results suggest that an improvement in modulation of AGE metabolism, which facilitates better management of circulating AGE levels, may be one of the mechanisms through which the Mediterranean diet, compared to a low-fat diet, reduces the progression of atherosclerosis in patients with CHD. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 , Clinicaltrials.gov number, NCT00924937.

Identifiants

pubmed: 39402581
doi: 10.1186/s12933-024-02451-4
pii: 10.1186/s12933-024-02451-4
doi:

Substances chimiques

Glycation End Products, Advanced 0
Receptor for Advanced Glycation End Products 0
Biomarkers 0
AGER protein, human 0
sRAGE protein, human 0
GLO1 protein, human EC 4.4.1.5
MOK protein, human EC 2.7.11.22
Antigens, Neoplasm 0
Lactoylglutathione Lyase EC 4.4.1.5
Mitogen-Activated Protein Kinases EC 2.7.11.24

Banques de données

ClinicalTrials.gov
['NCT00924937']

Types de publication

Journal Article Randomized Controlled Trial Comparative Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

361

Subventions

Organisme : Instituto de Salud Carlos III
ID : PI18/01822
Organisme : Consejería de Salud y Familias, Junta de Andalucía
ID : PC-0283-2017
Organisme : Ministerio de Ciencia e Innovación
ID : AGL2012-39615
Organisme : Fundación Patrimonio Comunal Olivarero
ID : Cordioprev-CEAS, 1/2016

Informations de copyright

© 2024. The Author(s).

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Auteurs

Francisco M Gutierrez-Mariscal (FM)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Alejandro Lopez-Moreno (A)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Jose D Torres-Peña (JD)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Purificacion Gomez-Luna (P)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Antonio P Arenas-de Larriva (AP)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Juan Luis Romero-Cabrera (JL)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Raul M Luque (RM)

CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.
Department of Cell Biology, Physiology and Immunology, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, University of Córdoba, 14004, Córdoba, Spain.

Jaime Uribarri (J)

Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Pablo Perez-Martinez (P)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Javier Delgado-Lista (J)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain.

Elena M Yubero-Serrano (EM)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain. elena.yubero@ig.csic.es.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. elena.yubero@ig.csic.es.
Department of Food and Health, Instituto de la Grasa, Spanish National Research Council (CSIC), Seville, Spain. elena.yubero@ig.csic.es.

Jose Lopez-Miranda (J)

Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain. jlopezmir@uco.es.
CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. jlopezmir@uco.es.

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