Circulating ORM2 as a Biomarker of Metabolic Dysfunction: Evidence from the KADEM Study in Kuwaiti Adults

Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) share overlapping pathophysiological mechanisms, including insulin resistance and chronic inflammation. Recent evidence suggests that Orosomucoid-2 (ORM2), an acute-phase immunomodulatory protein, may play a role in metabolic regulation; however, its specific involvement in MAFLD remains unclear. This study examined the association between circulating ORM2 levels and the severity of hepatic steatosis, insulin resistance, and T2DM in a cohort of 449 adults. MAFLD was assessed using FibroScan^® with hepatic steatosis categorized by Controlled Attenuation Parameter (CAP) scores, while plasma ORM2 levels were measured via ELISA. Statistical analyses using Spearman correlation and multiple logistic regression revealed that elevated ORM2 levels were significantly correlated with greater hepatic steatosis, insulin resistance, triglycerides, ALT, and hip circumference (<i>p</i> < 0.001). Individuals with severe steatosis (CAP > 290 dB/m) had markedly higher ORM2 levels (312.3 ng/mL) compared to those with normal CAP scores (210.4 ng/mL; <i>p</i> < 0.001). ORM2 was identified as an independent predictor of steatosis severity and after adjusting for several metabolic variables (AOR = 1.005; 95% CI: 1.002-1.007). ROC analysis incorporating ORM2 and metabolic variables demonstrated strong predictive capability for MAFLD (AUC = 0.864, 95% CI: 0.825-0.902). These findings support ORM2 as a promising non-invasive diagnosis for MAFLD, involving only blood sampling without direct invasion of the liver and associated metabolic dysfunction.