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Updated: May 11, 2025
An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes
Published on: April 26, 2019
Phenotypic patterns of metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: The impact of
Queralt Martín-Saladich1,2, Rafael Simó3,4, Andreea Ciudin3,4
1Medical Molecular Imaging Research Group, Vall d'Hebron Research Institute (VHIR), Nuclear Medicine, Radiology and Cardiology Departments, Vall d'Hebron University Hospital (VHUH), Autonomous University Barcelona (UAB), Barcelona, Spain.
Background:
Metabolic dysfunction-associated steatotic liver disease (MASLD) often leads to hepatic insulin resistance (IR), yet its link to liver-specific insulin-mediated glucose uptake (IGLU) in type 2 diabetes (T2D) remains unclear. We aimed to explore this MASLD-T2D relationship, addressing organ-specific IR for personalized management and risk prevention.
Methods:
This cross-sectional study included 41 T2D participants enrolled in a clinical trial (NCT02248311) undergoing biochemical analyses, anthropometric measurements and [18F]FDG-PET/CT imaging before and after hyperinsulinemic euglycemic clamp (HEC).
Findings:
Two MASLD-T2D phenotypes were identified according to their IGLU patterns, that is, with low (HepGluc[+], n = 21) and with high (HepGluc[-], n = 20) hepatic response to insulin. HepGluc[+] participants exhibited increased systemic IR (HOMA-IR, p = .012), inflammation (interleukin 6, p = .005); alanine and aspartate aminotransferase ALT, AST (p = .015 and p = .007); gamma-glutamyl transferase GGT (p = .019) and steatosis markers (liver volume, p = .006); NAFLD liver fat score, p = .0017; hepatic steatosis index, p = .02; fatty liver index, p = .008; liver stiffness measurements (LSM) (p = .049). No statistical differences in serum-based liver fibrosis scores were shown. To identify MASLD-T2D phenotypes in a friendly manner, the MASLD-T2D score based on support vector machines was developed using AST, ALT and GGT (AUC = .83), as well as with MASLD indices including LSM and NAFLD liver fat score (AUC = .90).
Implications:
Two new MASLD-T2D phenotypes have been identified, HepGluc[+] and HepGluc[-], according to IGLU patterns, with HepGluc[+] being more deleterious due to higher systemic IR, steatosis and inflammation. Phenotypes can be identified using a new function, the MASLD-T2D score.
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