Key result
Unified cardiometabolic framework links T2DM, ASCVD, HFpEF, and CKD to progressive visceral adipose dysfunction.
Why the study?
T2DM, ASCVD, HFpEF, MASLD, hypertension, and CKD share risk factors and may represent endpoints along a unified pathophysiological cardiometabolic disease continuum.
Reframing distinct cardiometabolic conditions as stages of a single continuum provides a mechanistic rationale for using pleiotropic therapies like GLP-1 RAs and SGLT2 inhibitors.
Offers a unifying cardiometabolic staging model; leaves open prospective validation of visceral adipose tissue-targeted therapies.
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.
No takes yet. Share an insight, caveat, or question.
Quirino-Vela et al. (2026) conducted a review in Cardiometabolic disease (T2DM, ASCVD, HFpEF, MASLD, hypertension, CKD). Unified cardiometabolic disease continuum was evaluated. The unified cardiometabolic disease continuum framework integrates T2DM, ASCVD, MASLD, HFpEF, hypertension, and CKD as progressive stages of a single pathophysiological process driven by visceral adipose tissue dysfunction.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: