Plasma metabolite predictors of metabolic syndrome incidence and reversion
Artikel i vetenskaplig tidskrift, 2024

Background: Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion. Methods: The study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association of 385 annotated metabolites with MetS incidence and MetS reversion after adjusting for potential risk factors. Results: Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.8-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR: 1.56 (95 % CI: 1.33–1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR: 1.44 (95 % CI: 1.25–1.67)), both p < 0.001. The MetS incidence and reversion signatures included several lipids (mainly glycerolipids and glycerophospholipids) and branched-chain amino acids. Conclusion: We identified unique metabolomic signatures, primarily comprised of lipids (including glycolipids and glycerophospholipids) and branched-chain amino acids robustly associated with MetS incidence; and several amino acids and glycerophospholipids associated with MetS reversion. These signatures provide novel insights on potential distinct mechanisms underlying the conditions leading to the incidence or reversion of MetS.

Metabolic syndrome

PREDIMED

Metabolomics

Metabolic syndrome reversion

Metabolic syndrome incidence

Författare

Zhila Semnani-Azad

Harvard School of Public Health

Estefania Toledo

Universidad de Navarra

Instituto de Investigación Sanitaria de Navarra (IdiSNA)

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Nancy Babio

Sant Joan de Reus University Hospital

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Universitat Rovira i Virgili

Miguel Ruiz-Canela

Instituto de Investigación Sanitaria de Navarra (IdiSNA)

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Universidad de Navarra

Clemens Wittenbecher

Chalmers, Life sciences, Livsmedelsvetenskap

Cristina Razquin

Universidad de Navarra

Instituto de Investigación Sanitaria de Navarra (IdiSNA)

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Fenglei Wang

Harvard School of Public Health

Courtney Dennis

Broad Institute

Amy Deik

Broad Institute

Clary B. Clish

Broad Institute

Dolores Corella

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Universitat de Valencia

Montserrat Fitó

Hospital del Mar Medical Research Institute

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Ramon Estruch

Universitat de Barcelona

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Fernando Aros

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Universidad del Pais Vasco / Euskal Herriko Unibertsitatea

Hospital Universitario Araba

Emilio Ros

Universitat de Barcelona

Jesús F. García-Gavilán

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Universitat Rovira i Virgili

Liming Liang

Harvard School of Public Health

Jordi Salas-Salvadó

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Sant Joan de Reus University Hospital

Universitat Rovira i Virgili

Miguel A. Martínez-González

Universidad de Navarra

Harvard School of Public Health

Instituto de Investigación Sanitaria de Navarra (IdiSNA)

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Frank B. Hu

Harvard School of Public Health

Brigham and Women's Hospital

Marta Guasch-Ferré

Novo Nordisk Fonden

Harvard School of Public Health

Metabolism: Clinical and Experimental

0026-0495 (ISSN) 15328600 (eISSN)

Vol. 151 155742

Ämneskategorier

Endokrinologi och diabetes

Kardiologi

Näringslära

DOI

10.1016/j.metabol.2023.155742

PubMed

38007148

Mer information

Senast uppdaterat

2023-12-22