Observational Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2025; 17(6): 104693
Published online Jun 27, 2025. doi: 10.4254/wjh.v17.i6.104693
Relationship between glucagon and metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus
Yi Sun, Ping Huang, Xiao-Qin Zhao, Zhu-Qi Tang, Tong-Tong Xu, Xin-Wei Wang, Zong-Xian Qi, Wei-Rong Lin, Min-You Li, Yun-Juan Gu
Yi Sun, Ping Huang, Xiao-Qin Zhao, Zhu-Qi Tang, Tong-Tong Xu, Xin-Wei Wang, Yun-Juan Gu, Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong 226000, Jiangsu Province, China
Zong-Xian Qi, Wei-Rong Lin, Min-You Li, R&D Department, Guangzhou Jinde Biotech Company Limited, Guangzhou 510000, Guangdong Province, China
Co-first authors: Yi Sun and Ping Huang.
Author contributions: Sun Y and Huang P contribute equally to this study as co-first authors; Sun Y wrote the first draft (including substantive translation); Huang P analyzed or synthesized the study data; Zhao XQ and Tang ZQ validated the results; Xu TT and Wang XW performed the experiments and data collection; Qi ZX and Lin WR provided the study materials, instrumentation, and analytical tools; Li MY managed and coordinated the planning and implementation of the research activities; Gu YJ designed the study.
Supported by Nantong Municipal Science and Technology Project, No. MS22019005, No. MSZ2023155 and No. JCZ2023004; Nantong University Hospital Research Hospital Construction Project, No. YJXYY202204-XKB09; and Guangzhou Jinde Biotechnology Company Self-selected Clinical Research Projects, No. HXKT20221024.
Institutional review board statement: The study was reviewed and approved by the ethics committee of Nantong University Affiliated Hospital (Approval No. 2018-k016).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors disclosed no potential conflict of interest relevant to this article.
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.
Data sharing statement: Dataset available from the corresponding author at desette@ntu.edu.cn. Participants gave informed consent for data sharing and the presented data are anonymized and risk of identification is low.
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: Yun-Juan Gu, Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong 226000, Jiangsu Province, China. desette@ntu.edu.cn
Received: December 31, 2024
Revised: March 18, 2025
Accepted: May 26, 2025
Published online: June 27, 2025
Processing time: 177 Days and 19.7 Hours
Abstract
BACKGROUND

Glucagon (GCG) plays an important role in both diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD).

AIM

To investigate the relationship between GCG and the development of MASLD in patients with type 2 diabetes mellitus (T2DM) and the possible influencing factors.

METHODS

A total of 212 T2DM patients were enrolled. GCG concentrations were measured using the chemiluminescence method. Fibro touch ultra sound attention parameter was used to determine the occurrence of MASLD. Multivariate logistic regression analyses were employed to assess the correlation between GCG levels and MASLD severity in T2DM patients.

RESULTS

The ultrasound attenuation parameter of T2DM patients was positively correlated with GCG, insulin (INS), C-peptide (CP), INS resistance, obesity related indicators (body mass index, waist circumference, percent body fat, basal metabolic rate, visceral fat area, fat free mass index, fat mass index, skeletal muscle index), liver cirrhosis related indicators [liver stiffness measurement (LSM), gamma glutamyl transpeptidase to platelet ratio, alanine aminotransferase], serum uric acid, diastolic blood pressure and triglyceride, while were negative correlated with age, fibrosis 4 score and high-density lipoprotein cholesterol (all P < 0.05). According to the multivariate logistic regression model, the T2DM patients with fasting GCG concentrations above the cut-off value had a significant increased risk of MASLD (OR: 3.068; 95%CI: 1.333-7.064; P = 0.008). Also, an increased concentration of fasting CP (OR: 1.965; 95%CI: 1.323-2.918; P = 0.001) and LSM (OR: 1.422; 95%CI: 1.16-1.743; P = 0.001) were significantly associated with a higher risk of MASLD in T2DM patients.

CONCLUSION

Fasting GCG, fasting CP and LSM are risk factors for MASLD in T2DM patients.

Keywords: Glucagon; Metabolic dysfunction-associated steatotic liver disease; Type 2 diabetes mellitus; Liver stiffness measurement; Ultrasound attenuation parameter

Core Tip: Our study aims to explore the relationship between glucagon (GCG) and the development of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 2 diabetes mellitus (T2DM) patients, and the possible influencing factors. A total of 212 patients with T2DM were enrolled. We categorized the study subjects into two groups with and without MASLD by the ultrasound attenuation parameter (244 dB/m as cut-off value). We find fasting GCG, fasting C-peptide and liver stiffness measurement are risk factors for MASLD in patients with T2DM.