04cae5a591fc8e61254b62b06c7a9bf3 jcm-14-08413.pdf 14db1ce8958d4006513f559d75f29b2b34c0e2bc jcm-14-08413.pdf 39c57cdfc91336db6dae9afa61dc7fdade765fcd3680521b6f8b97d0402c951f jcm-14-08413.pdf Title: Epicardial Fat and Heart Failure in Type 2 Diabetes: Metabolism, Imaging and Novel Biomarkers—A Translational Perspective Subject: Heart failure (HF) is a major cardiovascular complication in people with type 2 diabetes (T2D), where heart failure with preserved ejection fraction (HFpEF) is the most common presentation. Despite its high prevalence, HF in T2D often remains undiagnosed during its early stages due to nonspecific symptoms and the limitations of conventional diagnostic tools. Epicardial adipose tissue (EAT), a visceral fat depot surrounding the myocardium, has emerged as a mechanistic and clinically relevant contributor to myocardial dysfunction. In T2D, EAT expansion fosters a pro-inflammatory, fibrotic, and metabolically adverse milieu that may directly promote the onset and progression of HF. This perspective synthesizes current translational evidence on the role of EAT in the pathogenesis of HF among individuals with T2D. We highlight diagnostic challenges related to imaging-based quantification and the limited sensitivity of natriuretic peptide-based screening, while emphasizing the potential relevance of emerging biomarkers such as GDF-15, Galectin-3, sST2, LDL particle size, GGT, and soluble low-density lipoprotein receptor-related protein 1 (sLRP1) to enhance early detection and risk stratification. Additionally, therapeutic approaches—including lifestyle modification, SGLT2 inhibitors, and GLP-1 receptor agonists—are considered for their potential to modulate EAT volume and reduce cardiovascular risk. Advancing knowledge on EAT biology and its circulating biomarkers holds promise to refine HF risk stratification and support translational efforts toward precision cardiometabolic care. Keywords: epicardial adipose tissue (EAT); type 2 diabetes; heart failure with preserved ejection fraction (HFpEF); inflammatory biomarkers; sLRP1; GDF15; Galectin-3; sST2; LDL particle size; cardiac imaging Author: Pedro Gil-Millan, José Rives, José Luis Sánchez-Quesada and Antonio Pérez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Sat Nov 29 15:17:30 2025 CET ModDate: Sun Nov 30 11:58:36 2025 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 24 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1339630 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JINMPK+VnURWPalladioL Type 1 Custom yes yes yes 152 0 OFYESX+URWPalladioL-Bold Type 1 Custom yes yes yes 153 0 TRSXAK+URWPalladioL-Roma Type 1 Custom yes yes yes 154 0 DVVQHE+URWPalladioL-Ital Type 1 Custom yes yes yes 155 0 LHCXDL+EURM10 Type 1 Builtin yes yes yes 240 0 IEOPFG+PalatinoLinotype TrueType WinAnsi yes yes no 200 0 IEOPFG+PalatinoLinotype TrueType WinAnsi yes yes no 281 0 TNHTZS+CMSY10 Type 1 Builtin yes yes yes 338 0 IEOPFG+PalatinoLinotype TrueType WinAnsi yes yes no 617 0 IEOPFG+PalatinoLinotype TrueType WinAnsi yes yes no 648 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-03-06 05:06:27 CET RepresentationInformation: jcm-14-08413.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-03-05 16:13:40 CET Size: 1339630 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 917 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Children: Item: Title: Aim of the Review Item: Title: Heart Failure in Type 2 Diabetes Item: Title: Diabetic Cardiomyopathy: A Distinct Clinical Entity Item: Title: Visceral Adiposity and Cardiac Dysfunction Item: Title: The Role of Epicardial Adipose Tissue in the Development of Heart Failure Children: Item: Title: Anatomy and Physiological Role Item: Title: EAT Expansion and Mechanical Constraint Item: Title: Endocrine and Paracrine Activity of EAT Item: Title: EAT as a Metabolic and Inflammatory Buffer Item: Title: Limitations in Traditional Diagnostic Approaches for Heart Failure in Type 2 Diabetes Children: Item: Title: Plasma Biomarkers Item: Title: Imaging Analysis Item: Title: Novel Biomarkers of Epicardial Fat and Heart Failure Children: Item: Title: Adiponectin and Leptin Item: Title: Resistin and Apelin Item: Title: Interleukin 6 Item: Title: Soluble LRP1 (sLRP1) Item: Title: Small Dense LDL and GGT Item: Title: Galectin-3 Item: Title: Soluble ST2 (sST2) Item: Title: Growth Differentiation Factor 15 (GDF-15) Item: Title: Integration of Plasma Biomarkers with EAT and Translational Evidence Item: Title: Therapeutic Interventions: Impact on Heart Failure, Epicardial Adipose Tissue, and Biomarkers Item: Title: Conclusions Item: Title: References Info: Title: Epicardial Fat and Heart Failure in Type 2 Diabetes: Metabolism, Imaging and Novel Biomarkers—A Translational Perspective Author: Pedro Gil-Millan, José Rives, José Luis Sánchez-Quesada and Antonio Pérez Subject: Heart failure (HF) is a major cardiovascular complication in people with type 2 diabetes (T2D), where heart failure with preserved ejection fraction (HFpEF) is the most common presentation. Despite its high prevalence, HF in T2D often remains undiagnosed during its early stages due to nonspecific symptoms and the limitations of conventional diagnostic tools. Epicardial adipose tissue (EAT), a visceral fat depot surrounding the myocardium, has emerged as a mechanistic and clinically relevant contributor to myocardial dysfunction. In T2D, EAT expansion fosters a pro-inflammatory, fibrotic, and metabolically adverse milieu that may directly promote the onset and progression of HF. This perspective synthesizes current translational evidence on the role of EAT in the pathogenesis of HF among individuals with T2D. We highlight diagnostic challenges related to imaging-based quantification and the limited sensitivity of natriuretic peptide-based screening, while emphasizing the potential relevance of emerging biomarkers such as GDF-15, Galectin-3, sST2, LDL particle size, GGT, and soluble low-density lipoprotein receptor-related protein 1 (sLRP1) to enhance early detection and risk stratification. Additionally, therapeutic approaches—including lifestyle modification, SGLT2 inhibitors, and GLP-1 receptor agonists—are considered for their potential to modulate EAT volume and reduce cardiovascular risk. Advancing knowledge on EAT biology and its circulating biomarkers holds promise to refine HF risk stratification and support translational efforts toward precision cardiometabolic care. 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