Association of Epicardial Adipose Tissue with Novel Inflammation and Heart Failure Biomarkers in Type 2 Diabetes Patients: Effect of Metabolic Control
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Laboratory Analysis
2.3. Image Analysis
2.4. Statistical Analysis
3. Results
3.1. Clinical Characteristics
3.2. iEAT Volume and Left-Ventricular Function
3.3. Biomarkers of Inflammation
3.4. Novel HF-Related Biomarkers
3.5. EAT and Novel HF-Related Biomarkers
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AGEs | advanced glycation end-products |
ALP | alkaline phosphatase |
ALT | alanine transaminase |
AST | aspartate aminotransferase |
AW | abdominal waist |
BMI | body mass index |
BNP | B-type natriuretic peptide |
CVD | cardiovascular disease |
DPP4i | dipeptidyl peptidase-4 inhibitor |
EAT | epicardial adipose tissue |
EATv | epicardial adipose tissue volume |
EDV | end-diastolic volume left ventricular |
eGFR | estimated glomerular filtration rate |
ESV | end-systolic volume left ventricular |
FFAs | free fatty acids |
GDF15 | growth differentiation factor 15 |
GGC | good glycemic control |
GGT | gamma-glutamyl transferase |
GLP1-ar | glucagon-like peptide 1 agonist receptor |
HC | healthy controls |
HDLc | high-density lipoprotein cholesterol |
HF | heart failure |
HFpEF | heart failure with preserved ejection fraction |
HFrEF | heart failure with reduced ejection fraction |
hsCRP | high-sensitivity C-reactive protein |
hsTnT | high-sensitivity Troponin T |
iEAT | indexed epicardial adipose tissue |
IL | interleukin |
IR | insulin resistance |
LDLc | low-density lipoprotein cholesterol |
LVEF | Left-ventricular ejection fraction |
MDCT | multidetector computed tomography |
MRI | magnetic resonance imaging |
NPs | natriuretic peptides |
NT-proBNP | N-terminal pro-B-type natriuretic peptide |
PGC | poor glycemic control |
ROS | reactive oxygen species |
sHF | subclinical heart failure |
sST2 | soluble suppression of tumorigenicity 2 |
T1D | type 1 diabetes |
T2D | type 2 diabetes |
TC | total cholesterol |
Tg | triglycerides |
TNFα | tumor necrosis factor alpha |
VAT | visceral adipose tissue |
VIF | variance inflation factor |
VLDLc | very low density lipoprotein cholesterol |
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Spearman’s Rank Correlation Coefficient Test | |||
---|---|---|---|
r | p | ||
IL1β | HbA1c | 0.295 | 0.006 |
hsCRP | 0.259 | 0.013 | |
AST | 0.272 | 0.010 | |
LVEF | −0.293 | 0.029 | |
Tg | −0.250 | 0.016 | |
IL6 | BMI | 0.247 | 0.015 |
AW | 0.252 | 0.016 | |
HbA1c | 0.339 | 0.002 | |
hsCRP | 0.563 | <0.001 | |
AST | 0.304 | 0.004 | |
HDL-c | −0.235 | 0.022 | |
TNFα | AW | 0.208 | 0.038 |
HbA1c | 0.268 | 0.012 | |
hsCRP | 0.342 | 0.002 | |
AST | 0.261 | 0.013 | |
ALT | 0.232 | 0.023 | |
ALP | 0.258 | 0.013 | |
iEATv | 0.242 | 0.021 | |
LVEF | −0.263 | 0.025 | |
HDL-c | −0.373 | <0.001 | |
Adiponectin | Age | 0.192 | 0.046 |
ALT | −0.439 | <0.001 | |
GGT | −0.333 | 0.002 | |
Tg | −0.259 | 0.013 | |
HDL-c | 0.328 | 0.002 | |
VLDL-c | −0.241 | 0.020 | |
Leptin | Weight | 0.468 | <0.001 |
BMI | 0.653 | <0.001 | |
AW | 0.553 | <0.001 | |
ALT | 0.243 | 0.018 | |
hsCRP | 0.310 | 0.004 | |
Resistin | BMI | 0.258 | 0.012 |
AW | 0.251 | 0.016 | |
HbA1c | 0.268 | 0.012 | |
hsCRP | 0.298 | 0.005 |
Spearman’s Rank Correlation Coefficient Test | |||||||
---|---|---|---|---|---|---|---|
GDF15 | Galectin-3 | sST2 | |||||
r | p | r | p | r | p | ||
Clinical | Age | 0.56 | <0.0001 | 0.26 | 0.022 | 1 | 1 |
BMI | 0.23 | 0.04 | 0.27 | 0.02 | 0.28 | 0.015 | |
Weight | 0.18 | 0.10 | 0.09 | 0.41 | 0.35 | 0.002 | |
AW | 0.27 | 0.028 | 0.25 | 0.034 | 0.31 | 0.009 | |
Biochemical | HbA1c | 0.35 | 0.002 | 0.27 | 0.026 | 0.26 | 0.029 |
Glucose | 0.31 | 0.006 | 0.23 | 0.053 | 0.37 | 0.001 | |
ALP | 0.29 | 0.010 | 0.25 | 0.033 | 0.14 | 0.22 | |
GGT | 0.27 | 0.020 | −0.92 | 0.44 | 0.24 | 0.04 | |
HDL-c | −0.46 | <0.001 | −0.19 | 0.11 | −0.19 | 0.10 | |
LDL-c | −0.28 | 0.016 | −0.24 | 0.84 | −0.50 | 0.67 | |
Inflammation | hsCRP | 0.31 | 0.008 | 0.27 | 0.02 | 0.09 | 0.42 |
TNFα | 0.37 | <0.001 | 0.052 | 0.66 | 0.097 | 0.40 | |
IL6 | 0.25 | 0.02 | 0.27 | 0.02 | −0.058 | 0.61 | |
Cardiac Parameters | iEAT | 0.52 | <0.001 | 0.19 | 0.11 | 0.37 | <0.001 |
LVEF | 0.055 | 0.68 | 0.19 | 0.16 | −0.30 | 0.025 |
Multivariable Lineal Regression Analysis (Stepwise) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Model | Unstandardized Coefficients | Standardized Coefficients | t | p | 95.0% Confidence Interval for B | Collinearity Statistics | ||||
B | Std. Error | Beta | Lower Bound | Upper Bound | Tolerance | VIF | ||||
GDF15 | ||||||||||
1 | (Constant) | −2623.37 | 1039.69 | −2.52 | 0.014 | −4701.70 | −545.05 | |||
Age | 80.60 | 18.40 | 0.48 | 4.38 | 0.001 | 43.82 | 117.38 | 1.00 | 1.00 | |
2 | (Constant) | −2520.87 | 1007.47 | −2.50 | 0.015 | −4535.44 | −506.31 | 0.79 | 1.25 | |
Age | 60.03 | 19.98 | 0.36 | 3 | 0.004 | 20.08 | 99.98 | 0.79 | 1.25 | |
iEAT | 19.41 | 8.54 | 0.27 | 2.27 | 0.027 | 2.32 | 36.51 | |||
Galectin-3 | ||||||||||
1 | (Constant) | 20.57 | 2.36 | 8.70 | 0.001 | 15.85 | 25.30 | |||
HbA1c | 0.64 | 0.26 | 0.297 | 2.42 | 0.01 | 0.11 | 1.17 | 1.00 | 1.00 | |
2 | (Constant) | 20.90 | 2.25 | 9.7 | 0.001 | 16.40 | 25.41 | |||
HbA1c | 0.32 | 0.28 | 0.14 | 1.5 | 0.25 | −0.23 | 0.88 | 0.81 | 1.22 | |
hsCRP | 0.44 | 0.16 | 0.34 | 2.69 | 0.009 | 0.11 | 0.77 | 0.81 | 1.22 | |
sST2 | ||||||||||
1 | (Constant) | 12.91 | 3.61 | 3.57 | <0.01 | 5.67 | 20.14 | |||
HbA1c | 0.90 | 0.40 | 0.28 | 2.21 | 0.031 | 0.08 | 1.72 | 1.00 | 1.00 | |
2 | (Constant) | −7.06 | 9.27 | −0.76 | 0.44 | −25.64 | 11.50 | |||
HbA1c | 0.74 | 0.40 | 0.23 | 1.84 | 0.07 | −0.063 | 1.54 | 0.96 | 1.03 | |
AW | 0.19 | 0.08 | 0.28 | 2.32 | 0.024 | 0.027 | 0.37 | 0.96 | 1.03 | |
3 | (Constant) | −5.27 | 8.99 | −0.58 | 0.56 | −23.29 | 12.74 | |||
HbA1c | 0.56 | 0.39 | 0.17 | 1.42 | 0.16 | −0.22 | 1.35 | 0.92 | 1.07 | |
AW | 0.12 | 0.08 | 0.18 | 1.43 | 0.15 | −0.05 | 0.30 | 0.84 | 1.18 | |
iEAT | 0.14 | 0.06 | 0.29 | 2.24 | 0.02 | 0.01 | 0.26 | 0.81 | 1.22 |
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Gil-Millan, P.; Rives, J.; Viladés, D.; García-Osuna, Á.; Genua, I.; Miñambres, I.; Grau-Agramunt, M.; Gich, I.; Camacho, M.; Benitez, S.; et al. Association of Epicardial Adipose Tissue with Novel Inflammation and Heart Failure Biomarkers in Type 2 Diabetes Patients: Effect of Metabolic Control. J. Clin. Med. 2025, 14, 4687. https://doi.org/10.3390/jcm14134687
Gil-Millan P, Rives J, Viladés D, García-Osuna Á, Genua I, Miñambres I, Grau-Agramunt M, Gich I, Camacho M, Benitez S, et al. Association of Epicardial Adipose Tissue with Novel Inflammation and Heart Failure Biomarkers in Type 2 Diabetes Patients: Effect of Metabolic Control. Journal of Clinical Medicine. 2025; 14(13):4687. https://doi.org/10.3390/jcm14134687
Chicago/Turabian StyleGil-Millan, Pedro, José Rives, David Viladés, Álvaro García-Osuna, Idoia Genua, Inka Miñambres, Margarita Grau-Agramunt, Ignasi Gich, Mercedes Camacho, Sonia Benitez, and et al. 2025. "Association of Epicardial Adipose Tissue with Novel Inflammation and Heart Failure Biomarkers in Type 2 Diabetes Patients: Effect of Metabolic Control" Journal of Clinical Medicine 14, no. 13: 4687. https://doi.org/10.3390/jcm14134687
APA StyleGil-Millan, P., Rives, J., Viladés, D., García-Osuna, Á., Genua, I., Miñambres, I., Grau-Agramunt, M., Gich, I., Camacho, M., Benitez, S., Julve, J., Sánchez-Quesada, J. L., & Pérez, A. (2025). Association of Epicardial Adipose Tissue with Novel Inflammation and Heart Failure Biomarkers in Type 2 Diabetes Patients: Effect of Metabolic Control. Journal of Clinical Medicine, 14(13), 4687. https://doi.org/10.3390/jcm14134687