Fetuin-A. A potential molecular link between obesity, diabetes (type 2 and type 1) and metabolic steatotic liver disease (MASLD)

Purpose: Fetuin-A represents a novel molecular target involved in the complex pathogenesis of metabolic disorders. This study aimed to evaluate its association with obesity, type 2 (T2DM) and type 1 (T1DM) diabetes and its correlation with non-invasive liver assessment. Methods: 105 patients (38 with obesity without T2DM, 30 with T2DM, and 37 with T1DM) and 13 controls were included. All participants underwent transient elastography (TE) with controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), clinical and biochemical data (including fetuin-A). Results: Fetuin-A was significantly higher in all clinical groups than controls, with the greatest increase observed in obesity without T2DM. Fetuin-A correlated positively with measures of adiposity (BMI, waist circumference, waist to height ratio), triglycerides, and non-invasive indicators of liver steatosis (Fatty Liver Index and CAP), while showing no association with fibrosis (defined by LSM ≥ 7.9 kPa). In age- and sex-adjusted models, fetuin-A remained independently associated with obesity and T1DM, whereas T2DM showed a negative but not significant association. Fetuin-A was significantly higher in steatosis, with good discriminatory ability (AUC 0.84, 95% CI 0.77-0.91) and a sensitivity of 0.75 and specificity of 0.74 at the optimal Youden threshold. Negative association with male sex and positive association with age was also observed. Conclusions: Results confirm fetuin-A as a molecular signature of metabolic disorders, mediating the cross-talk between liver and adipose tissue. Further studies are needed to validate it as a useful biomarker for the early diagnosis and monitoring of liver and metabolic disease, including obesity, T2DM, T1DM, and MASLD, and to reach a consensus on reference values definition.