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

doi:10.4254/wjh.v17.i6.104693

Relationship between glucagon and metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus

World J Hepatol. 2025 Jun 27;17(6):104693. doi: 10.4254/wjh.v17.i6.104693.

Authors

Affiliations

¹ Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong 226000, Jiangsu Province, China.
² R&D Department, Guangzhou Jinde Biotech Company Limited, Guangzhou 510000, Guangdong Province, China.
³ Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong 226000, Jiangsu Province, China. desette@ntu.edu.cn.

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