{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:15:26Z","timestamp":1793823326594,"version":"4.6.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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-\u03baB\/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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Current evidence supports a mechanistic framework in which visceral adipose tissue dysfunction and ectopic lipid accumulation, progressing through ceramide-mediated lipotoxicity, NF-\u03baB\/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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1897556","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:07Z","timestamp":1783570987000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The unified cardiometabolic disease continuum: mechanistic stages of a single pathophysiological process"],"prefix":"10.3389","volume":"17","author":[{"given":"Luz Mar\u00eda","family":"Quirino-Vela","sequence":"first","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica, Facultad de Medicina y Cirug\u00eda, Universidad Aut\u00f3noma Benito Ju\u00e1rez de Oaxaca (UABJO)","place":["Oaxaca de Ju\u00e1rez, Oaxaca, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Mayoral-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica, Facultad de Medicina y Cirug\u00eda, Universidad Aut\u00f3noma Benito Ju\u00e1rez de Oaxaca (UABJO)","place":["Oaxaca de Ju\u00e1rez, Oaxaca, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Mat\u00edas-Cervantes","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica, Facultad de Medicina y Cirug\u00eda, Universidad Aut\u00f3noma Benito Ju\u00e1rez de Oaxaca (UABJO)","place":["Oaxaca de Ju\u00e1rez, Oaxaca, Mexico"]},{"name":"SECIHTI-Facultad de Medicina y Cirug\u00eda, UABJO","place":["Oaxaca de Ju\u00e1rez, Oaxaca, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yobana","family":"P\u00e9rez-Cervera","sequence":"additional","affiliation":[{"name":"Centro de Estudios en Ciencias de la Salud y la Enfermedad, Facultad de Odontolog\u00eda, Universidad Aut\u00f3noma Benito Ju\u00e1rez de Oaxaca","place":["Oaxaca de Ju\u00e1rez, Oaxaca, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n A.","family":"Garc\u00eda-Montalvo","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Tecnol\u00f3gico Nacional de M\u00e9xico\/Instituto Tecnol\u00f3gico de Oaxaca","place":["Oaxaca, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Alpuche","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica, Facultad de Medicina y Cirug\u00eda, Universidad Aut\u00f3noma Benito Ju\u00e1rez de Oaxaca (UABJO)","place":["Oaxaca de Ju\u00e1rez, Oaxaca, 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