Abu-Farha Mohamed, Albatineh Ahmed N, Alawadh Bader, Alsalem Loulwa, Al-Khairi Irina, Cherian Preethi, Al-Ajmi Fahad, Qaddoumi Mohammad, Abdul-Ghani Muhammad, Al-Mulla Fahd, Abubaker Jehad
Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Department of Translational Research, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Int J Mol Sci. 2025 Aug 27;26(17):8326. doi: 10.3390/ijms26178326.
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 ( < 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; < 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.
代谢功能障碍相关脂肪性肝病（MAFLD）和2型糖尿病（T2DM）具有重叠的病理生理机制，包括胰岛素抵抗和慢性炎症。最近的证据表明，血清类黏蛋白-2（ORM2），一种急性期免疫调节蛋白，可能在代谢调节中发挥作用；然而，其在MAFLD中的具体作用仍不清楚。本研究在449名成年人队列中，检测了循环ORM2水平与肝脂肪变性严重程度、胰岛素抵抗和T2DM之间的关联。使用FibroScan评估MAFLD，并通过受控衰减参数（CAP）评分对肝脂肪变性进行分类，同时通过ELISA测定血浆ORM2水平。使用Spearman相关性分析和多元逻辑回归进行统计分析，结果显示ORM2水平升高与更严重的肝脂肪变性、胰岛素抵抗、甘油三酯、谷丙转氨酶（ALT）和臀围显著相关（<0.001）。与CAP评分正常者（210.4 ng/mL）相比，重度脂肪变性（CAP>290 dB/m）的个体ORM2水平明显更高（312.3 ng/mL；<0.001）。ORM2被确定为脂肪变性严重程度的独立预测因子，在调整了几个代谢变量后（调整后比值比[AOR]=1.005；95%置信区间[CI]：1.002-1.007）。纳入ORM2和代谢变量的ROC分析显示对MAFLD具有较强的预测能力（曲线下面积[AUC]=0.864，95%CI：0.825-0.902）。这些发现支持ORM2作为一种有前景的MAFLD无创诊断指标，仅需采血，无需直接侵入肝脏及相关代谢功能障碍。
