Evidence mapPaperPMID 42494872Full record

ReviewFrontiers in endocrinology2026

The unified cardiometabolic disease continuum: mechanistic stages of a single pathophysiological process.

Luz María Quirino-Vela, Miguel A Mayoral-Chávez, Carlos A Matías-Cervantes, Yobana Pérez-Cervera, Iván A García-Montalvo, Juan Alpuche

Abstract readReview
In one paragraph

Review in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Luz María Quirino-VelaLaboratorio de Bioquímica, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca (UABJO), Oaxaca de Juárez, Oaxaca, Mexico.
Miguel A Mayoral-ChávezLaboratorio de Bioquímica, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca (UABJO), Oaxaca de Juárez, Oaxaca, Mexico.
Carlos A Matías-CervantesLaboratorio de Bioquímica, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca (UABJO), Oaxaca de Juárez, Oaxaca, Mexico.
Yobana Pérez-CerveraCentro de Estudios en Ciencias de la Salud y la Enfermedad, Facultad de Odontología, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez, Oaxaca, Mexico.
Iván A García-MontalvoDivisión de Estudios de Posgrado e Investigación, Tecnológico Nacional de México/Instituto Tecnológico de Oaxaca, Oaxaca, Mexico.
Juan AlpucheLaboratorio de Bioquímica, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca (UABJO), Oaxaca de Juárez, Oaxaca, Mexico.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Type 2 diabetes mellitus (T2DM), atherosclerotic cardiovascular disease (ASCVD), heart failure with preserved ejection fraction (HFpEF), metabolic dysfunction-associated steatotic liver disease (MASLD), hypertension, and chronic kidney disease (CKD) share risk factors and may represent endpoints of a pathophysiological cardiometabolic continuum. We analyzed data suggesting these phenotypes arise along a unified cardiometabolic disease (UCD) continuum with distinct stages, biomarkers, and therapeutic targets. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Searches combined terms for mechanistic drivers (visceral adipose tissue, ceramides, lipotoxicity, NF-κB/NLRP3 signaling, gut microbiota, TMAO, adipokines, endothelial dysfunction, epicardial fat, metabolic flexibility) and clinical endpoints. Priority was given to peer-reviewed translational studies, major outcome trials, and consensus statements published between 2017-2026. Results: Current evidence supports a mechanistic framework in which visceral adipose tissue dysfunction and ectopic lipid accumulation, progressing through ceramide-mediated lipotoxicity, NF-κB/NLRP3-driven inflammation, gut microbiome-derived endotoxemia and TMAO, adipokine dysregulation, endothelial dysfunction, epicardial fat-mediated cardiac remodeling, impaired metabolic flexibility, and a cardiorenal amplification loop. Stage-specific mediators (e.g., ceramides, NLRP3, TMAO, leptin-adiponectin ratio) serve as biomarkers. The benefits of GLP-1 receptor agonists, SGLT2 inhibitors, and finerenone across T2DM, ASCVD, HFpEF, MASLD, and CKD reflect pharmacologic modulation of this continuum. Discussion: Data support a UCD model where T2DM, ASCVD, MASLD, HFpEF, hypertension, and CKD are manifestations of a progressive pathophysiological continuum. Framing these conditions as stages of a continuum informs risk stratification, biomarker development, and mechanism-guided therapy, providing a framework for designing trials targeting the continuum rather than individual endpoints.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Metabolic DiseasesAnimalsBiomarkersGastrointestinal MicrobiomeHumansBiomarkerscardiometabolic continuumcardiometabolic riskceramidesepicardial adipose tissuegut microbiomeNLRP3 inflammasomepathophysiological processesunified cardiometabolic disease

Identifiers

PMID42494872
PMCPMC13391316

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.