Evidence map›Paper›PMID 41881293›Full record

ArticleMetabolism: clinical and experimental2026

Metabolomics profiles of type 2 diabetes and insulin resistance and their associations with total mortality.

Jesús F García-Gavilán, Indira Paz-Graniel, Josué A Pérez-Acosta, Miguel Ruiz-Canela, Jun Li, Clary Clish, Cristina Razquin, Huan Yun, Dolores Corella, Ramón Estruch and 13 more

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Article in Metabolism: clinical and experimental, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

23 authors.

Jesús F García-GavilánUniversitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Institut de Recerca Biomèdica Catalunya Sud (IRBCatSud), Reus, Spain.
Indira Paz-GranielUniversitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Institut de Recerca Biomèdica Catalunya Sud (IRBCatSud), Reus, Spain. Electronic address: indiradelsocorro.paz@urv.cat.
Josué A Pérez-AcostaUniversitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Institut de Recerca Biomèdica Catalunya Sud (IRBCatSud), Reus, Spain.
Miguel Ruiz-CanelaCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Department of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain.
Jun LiDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Clary ClishMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cristina RazquinCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Department of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain.
Huan YunDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Dolores CorellaCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Department of Preventive Medicine, University of Valencia, Valencia, Spain.
Ramón EstruchCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
Emilio RosCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain.
Montserrat FitóCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain.
Fenglei WangDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Miquel FiolCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Platform for Clinical Trials, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Palma de Mallorca, Spain.
José LapetraCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Seville, Spain.
Enrique Gómez-GraciaDepartment of Preventive Medicine, University of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.
Liming LiangDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Courtney DenisMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nancy BabioUniversitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Institut de Recerca Biomèdica Catalunya Sud (IRBCatSud), Reus, Spain.
Marta Guasch-FerréDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark.
Miguel Ángel Martínez-GonzálezCIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Department of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Frank B HuDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark.
Jordi Salas-SalvadóUniversitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Institut de Recerca Biomèdica Catalunya Sud (IRBCatSud), Reus, Spain. Electronic address: jordi.salas@urv.cat.

Funding

Mediterranean diet, Metabolites, and Cardiovascular DiseaseR01HL118264 · NHLBI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI HU, FRANK B, LAMUELA-RAVENTÓS, ROSA · 2013 to 2025
$6.8M
Lifestyle Interventions, metabolites, microbiome, and diabetes riskR01DK127601 · NIDDK · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI HU, FRANK B, RUIZ-CANELA, MIGUEL · 2021 to 2024
$1.9M
Dietary Interventions, Metabolites, and Risk of Type 2 DiabetesR01DK102896 · NIDDK · HARVARD SCHOOL OF PUBLIC HEALTH · PI HU, FRANK B, MARTINEZ GONZALEZ, MIGUEL A. · 2014 to 2017
$1.9M
NHLBI NIH HHS R01 HL118264NIDDK NIH HHS R01 DK102896NIDDK NIH HHS R01 DK127601
6 · The paper itself

Abstract

objectiveThis study aimed to identify metabolomic profiles associated with type 2 diabetes and insulin resistance (HOMA-IR) and relate them to the risk of total mortality.

methodsA longitudinal study was conducted in a subset of participants from a diabetes case-cohort study (mean age, 66.5 years; 62% women; 176/699 with incident T2D) within the PREDIMED trial. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year follow-up (validation sample). Multi-metabolite profile scores for type 2 diabetes and HOMA-IR, respectively, were derived using elastic net regression. Cox proportional hazards were fitted to assess the association between metabolomic profiles and total mortality, adjusting for potential confounders. External validation was performed in the NHS/HPFS cohorts.

resultsA total of 31 metabolites were associated with type 2 diabetes and 105 with HOMA-IR. Both metabolomic profiles were significantly associated with a higher risk of total mortality (type 2 diabetes HR = 1.52, 95%CI: 1.04-2.25; HOMA-IR HR = 1.33, 95%CI: 1.00-1.75) in the PREDIMED cohort. Shared metabolites between both metabolomic signatures, including glycine, SDMA, DMGV, and phosphocreatine, were associated with mortality. These associations were replicated in a pooled analysis of three independent American cohorts (type 2 diabetes HR = 1.09, 95%CI: 1.05-1.13; HOMA-IR HR = 1.04, 95%CI: 1.00-1.09).

conclusionsIn an older population at high cardiometabolic risk, metabolomic scores of type 2 diabetes and insulin resistance were associated with total mortality risk, potentially explaining some mechanisms behind the increased risk of mortality observed in epidemiological studies for individuals with glycemic dysregulations.

Indexed as

Diabetes Mellitus, Type 2Insulin ResistanceMetabolomeAgedFemaleHumansLongitudinal StudiesMaleMetabolomicsMiddle AgedBiomarkersDiabetesGlucose metabolismMetabolomic signatureMortalityPlasma metabolites

Identifiers

PMID41881293
PMCPMC13656857

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