Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Oct 26, 2024; 16(10): 580-594
Published online Oct 26, 2024. doi: 10.4330/wjc.v16.i10.580
Metabolic dysfunction-associated steatotic liver disease-associated fibrosis and cardiac dysfunction in patients with type 2 diabetes
Simona Cernea, Danusia Onișor, Andrada Larisa Roiban, Theodora Benedek, Nora Rat
Simona Cernea, Department M3/Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureş 540142, Romania
Simona Cernea, Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş 540136, Romania
Danusia Onișor, Department ME2/Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureş, Târgu Mureş 540142, Romania
Danusia Onișor, Gastroenterology Clinic, Mureș County Clinical Hospital, Târgu Mureş 540103, Romania
Andrada Larisa Roiban, Diabetes Compartment, Mediaș Municipal Hospital, Mediaș 551030, Romania
Andrada Larisa Roiban, Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, Târgu Mureş 540142, Romania
Theodora Benedek, Nora Rat, Department M3/Internal Medicine VI, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, Târgu Mureş 540142, Romania
Theodora Benedek, Nora Rat, Department of Cardiology, Emergency County Clinical Hospital, Târgu Mureş 540136, Romania
Author contributions: Cernea S design the study, acquired, analyzed and interpreted the data, wrote the manuscript, designed the figure; Onișor D, Roiban AL and Rat N acquired data and reviewed the paper for important intellectual content; Benedek T interpreted the data and reviewed the paper for important intellectual content.
Supported by the University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș Research Grant, No. 10126/5/17.12.2020.
Institutional review board statement: The study was approved by the Ethics Committees of the Emergency County Clinical Hospital of Târgu Mureș (nr. 8120/05.04.2022), the County Clinical Hospital of Târgu Mureș (nr. 4873/24.05.2022), and the George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș (nr. 1806/22.06.2022).
Informed consent statement: All subjects signed an informed consent before being enrolled in the study.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this paper.
Data sharing statement: Data may be available upon request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Simona Cernea, MD, PhD, Professor, Department M3/Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 38 Gheorghe Marinescu st., Târgu Mureş 540142, Romania. simonacernea@yahoo.com
Received: March 27, 2024
Revised: August 28, 2024
Accepted: September 19, 2024
Published online: October 26, 2024
Processing time: 204 Days and 3.6 Hours
Abstract
BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in the presence of liver fibrosis, increases the risk of cardiovascular morbidity and mortality, but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus (T2DM) is not fully understood.

AIM

To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis.

METHODS

T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle, anthropometric measurements, vital signs, an extensive laboratory panel, and a standard echocardiography. Liver fibrosis was evaluated using two scores [Fibrosis-4 (FIB4) and Non-alcoholic fatty liver disease-Fibrosis Score (NFS)], and subjects were classified as having advanced fibrosis, no fibrosis, or an indeterminate risk. The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses. Statistical significance was set at P < 0.05.

RESULTS

Data from 267 T2DM-MASLD subjects with complete assessment was analyzed. Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular (LV) posterior wall thickness, atrial diameters, LV end-systolic volume, LV mass index (LVMi), and epicardial adipose tissue thickness (EATT). Their mean ejection fraction (EF) was significantly lower (49.19% ± 5.62% vs 50.87% ± 5.14% vs 52.00% ± 3.25%; P = 0.003), and a smaller proportion had an EF ≥ 50% (49.40% vs 68.90% vs 84.21%; P = 0.0017). Their total and mid LV wall motion score indexes were higher (P < 0.05). Additionally, they had markers of diastolic dysfunction, with a higher E/e’ ratio [9.64 ± 4.10 vs 8.44 (2.43-26.33) vs 7.35 ± 2.62; P = 0.026], and over 70% had lateral e’ values < 10 cm/second, though without significant differences between groups. In multiple regression analyses, FIB4 correlated with left atrium diameter (LAD; β = 0.044; P < 0.05), and NFS with both LAD (β = 0.039; P < 0.05) and right atrium diameter (β = 0.041; P < 0.01), Moreover, LVMi correlated positively with age and EATT (β = 1.997; P = 0.0008), and negatively with serum sex-hormone binding protein (SHBP) concentrations (β = -0.280; P = 0.004). SHBP also correlated negatively with LAD (β = -0.036; P < 0.05).

CONCLUSION

T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy. Additionally, LVMi and LAD correlated negatively with serum SHBP concentrations.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Type 2 diabetes mellitus; Liver fibrosis; Cardiac dysfunction; Sex-hormone binding protein

Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) is frequently associated with type 2 diabetes mellitus (T2DM), and both conditions are important risk factors for cardiovascular disease. However, the nature of the cardio-liver interaction, particularly in patients with T2DM, is not completely elucidated. In this study we found that T2DM patients with MASLD-associated fibrosis, quantified by accessible scores (Fibrosis-4 and Non-alcoholic fatty liver disease-Fibrosis Score), present markers of systolic and diastolic dysfunction, as well as cardiac hypertrophy, particularly increased left atrial diameter. The left ventricular mass index and left atrial dimension also correlated negatively with serum concentrations of sex-hormone binding protein, which may serve as a valuable prognostic biomarker. Mechanistic studies that explain the correlations between liver fibrosis and cardiac remodeling in MASLD patients, both with and without T2DM, are greatly needed.