8ddfcd75b4efd23a53200461b24aa5bc jcm-14-04687.pdf 0bd9ef979c048548515361d10651a76774736048 jcm-14-04687.pdf 66b0862f64ca48130036ced9b8aed1fe2a8622f584afbac89c8faf19e8888cae jcm-14-04687.pdf Title: Association of Epicardial Adipose Tissue with Novel Inflammation and Heart Failure Biomarkers in Type 2 Diabetes Patients: Effect of Metabolic Control Subject: Background: Type 2 diabetes (T2D patients) have a 74% increased risk of heart failure (HF), but traditional HF biomarkers lack sensitivity in early disease detection. Increased epicardial adipose tissue volume (EATv) is associated with cardiovascular risk in T2D, and novel biomarkers such as growth differentiation factor 15 (GDF15), Galectin-3, and soluble suppression of tumorigenicity 2 (sST2) are inflammation biomarkers linked to HF. Methods: We investigated associations between EATv, inflammation biomarkers, and the effect of metabolic control in 14 healthy controls (HCs) and 36 newly diagnosed T2D patients both before (poor glycemic control, PGC) and after 12 months of glycemic optimization (good glycemic control, GGC). EATv indexed to body surface area (iEATv) was quantified by multidetector computed tomography, and biomarker levels were measured by immunoassays. Results: PGC patients had higher iEATv (59.53 21.67 vs. 36.84 16.57 cm3/m2, p = 0.0017) and elevated GDF15, Galectin-3, and sST2 levels (all p < 0.05) than HC subjects. The glycemic optimization reduced iEATv (p = 0.0232) and sST2 (p = 0.048), while GDF15 and Galectin-3 remained unchanged. Multivariable analysis confirmed independent associations between iEATv, GDF15 ( = 0.27, p = 0.027) and sST2 ( = 0.29, p = 0.02). Conclusions: These results support the link between systemic inflammation, EAT expansion, and cardiac dysfunction, and they point to the role of epicardial fat in early HF risk of T2D patients. Keywords: epicardial adipose tissue (EAT); type 2 diabetes (T2D); cardiovascular risk; heart failure (HF); inflammatory biomarkers; GDF15; Galectin-3; sST2; metabolic control (MC) Author: Pedro Gil-Millan, José Rives, David Viladés, Álvaro García-Osuna, Idoia Genua, Inka Miñambres, Margarita Grau-Agramunt, Ignasi Gich, Mercedes Camacho, Sonia Benitez, Josep Julve, José Luis Sánchez-Quesada and Antonio Pérez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Jul 2 13:18:23 2025 CEST ModDate: Wed Jul 2 13:21:16 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 552417 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QDCWHF+EURM10 Type 1 Builtin yes yes yes 10 0 JINMPK+VnURWPalladioL Type 1 Custom yes yes yes 15 0 OLOHMJ+URWPalladioL-Roma Type 1 Custom yes yes yes 21 0 CDWERA+URWPalladioL-Bold Type 1 Custom yes yes yes 27 0 NDGHIQ+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 VFNYCD+CMSY10 Type 1 Builtin yes yes yes 37 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 72 0 IBIJEF+Symbol Type 1C Custom yes yes yes 82 0 IBIJDF+Arial,Bold TrueType WinAnsi yes yes no 87 0 IBIJEH+Arial TrueType WinAnsi yes yes no 90 0 IBIHHG+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 93 0 IBIHHI+PalatinoLinotype TrueType WinAnsi yes yes no 96 0 IBIJDF+Arial,Bold TrueType WinAnsi yes yes no 107 0 IBIJEH+Arial TrueType WinAnsi yes yes no 110 0 IBIHHI+PalatinoLinotype TrueType WinAnsi yes yes no 113 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-10-21 03:49:03 CEST RepresentationInformation: jcm-14-04687.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-10-20 18:33:34 CEST Size: 552417 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 307 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Population Destination: subsection.2.1 Item: Title: Laboratory Analysis Destination: subsection.2.2 Item: Title: Image Analysis Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Clinical Characteristics Destination: subsection.3.1 Item: Title: iEAT Volume and Left-Ventricular Function Destination: subsection.3.2 Item: Title: Biomarkers of Inflammation Destination: subsection.3.3 Item: Title: Novel HF-Related Biomarkers Destination: subsection.3.4 Item: Title: EAT and Novel HF-Related Biomarkers Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Association of Epicardial Adipose Tissue with Novel Inflammation and Heart Failure Biomarkers in Type 2 Diabetes Patients: Effect of Metabolic Control Author: Pedro Gil-Millan, José Rives, David Viladés, Álvaro García-Osuna, Idoia Genua, Inka Miñambres, Margarita Grau-Agramunt, Ignasi Gich, Mercedes Camacho, Sonia Benitez, Josep Julve, José Luis Sánchez-Quesada and Antonio Pérez Subject: Background: Type 2 diabetes (T2D patients) have a 74% increased risk of heart failure (HF), but traditional HF biomarkers lack sensitivity in early disease detection. Increased epicardial adipose tissue volume (EATv) is associated with cardiovascular risk in T2D, and novel biomarkers such as growth differentiation factor 15 (GDF15), Galectin-3, and soluble suppression of tumorigenicity 2 (sST2) are inflammation biomarkers linked to HF. Methods: We investigated associations between EATv, inflammation biomarkers, and the effect of metabolic control in 14 healthy controls (HCs) and 36 newly diagnosed T2D patients both before (poor glycemic control, PGC) and after 12 months of glycemic optimization (good glycemic control, GGC). EATv indexed to body surface area (iEATv) was quantified by multidetector computed tomography, and biomarker levels were measured by immunoassays. Results: PGC patients had higher iEATv (59.53 21.67 vs. 36.84 16.57 cm3/m2, p = 0.0017) and elevated GDF15, Galectin-3, and sST2 levels (all p < 0.05) than HC subjects. The glycemic optimization reduced iEATv (p = 0.0232) and sST2 (p = 0.048), while GDF15 and Galectin-3 remained unchanged. Multivariable analysis confirmed independent associations between iEATv, GDF15 ( = 0.27, p = 0.027) and sST2 ( = 0.29, p = 0.02). Conclusions: These results support the link between systemic inflammation, EAT expansion, and cardiac dysfunction, and they point to the role of epicardial fat in early HF risk of T2D patients. Keywords: epicardial adipose tissue (EAT); type 2 diabetes (T2D); cardiovascular risk; heart failure (HF); inflammatory biomarkers; GDF15; Galectin-3; sST2; metabolic control (MC) Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Jul 02 13:18:23 CEST 2025 ModDate: Wed Jul 02 13:21:16 CEST 2025 ID: 0xa2531af4e5b38ee67879d17868c8858b, 0xa2531af4e5b38ee67879d17868c8858b Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: NDGHIQ+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: NDGHIQ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: VFNYCD+CMSY10 FontSubset: true FirstChar: 0 LastChar: 20 FontDescriptor: FontName: VFNYCD+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true ToUnicode: true Font: BaseFont: OLOHMJ+URWPalladioL-Roma FontSubset: true FirstChar: 1 LastChar: 250 FontDescriptor: FontName: 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