2465-P: FGF21 Is Related to Insulin Secretion during OGTT in Patients with High MASLD Probability: Preliminary Data from a Human Cohort

Introduction and Objective: FGF21 is a signaling protein belonging to the fibroblast growth factors family, mainly secreted by liver. Among its other roles, it is involved in glucose and lipid metabolism, enhancing glucose absorption and increasing fatty acid oxidation, and it is strongly influenced by metabolic status of the liver. We therefore aimed to assess if 1) FGF21 correlates with basal insulin secretion and 2) MASLD could impact its basal levels. Methods: We analyzed FGF21 levels in a subgroup of 28 subjects (21 (75%) females, median (IQR) age 53 (47, 59) years) with high MASLD probability who underwent a modified oral glucose tolerance test (OGTT) estimating insulin sensitivity and secretion from OGTT-derived parameters through a model-based method. We estimated MASLD probability through Fatty Liver Index (FLI). Results: Our sample had a median (IQR) BMI of 33.9 (30.1, 38.2) kg/m2, with an FLI of 81.8 (63.5, 96.9). Basal levels of FGF21 (median (IQR) of 234 (110, 354) pg/mL) were significantly correlated with model-derived basal insulin secretion (Spearman’s rho= 0.43, p = 0.02), also when adjusting for age, sex, BMI, FLI, and basal glucose levels (β coefficient = 1.23, p = 0.049). Conclusion: To date, this study represents the first investigation demonstrating an association between FGF21 levels and insulin secretion in a human cohort with a high probability of MASLD. Further studies in larger populations are warranted to better elucidate the role of FGF21 in glucose metabolism and its secretion profile. Disclosure F. Sileo: None. A. Foppiani: None. B. Marelli: None. A. Mari: Consultant; Current; Lilly, Novo Nordisk. A. Battezzati: None.