非酒精性脂肪性肝病合并2型糖尿病患者血清FGF-21和microRNA-21水平的变化及其临床意义

Serum levels of FGF-21 and miR-21 in patients with non-alcoholic fatty liver disease and type 2 diabetes: changes and clinical significance

摘要:

目的 探讨非酒精性脂肪性肝病（NAFLD）合并2型糖尿病患者血清成纤维细胞生长因子-21（FGF-21）和microRNA-21（miR-21）水平变化及其临床意义。方法 选取2020年1月—2024年1月聊城市第二人民医院收治的106例NAFLD合并2型糖尿病患者，根据患者NAFLD纤维化程度，将进展性纤维化患者作为观察组（27例），非进展性肝纤维化患者作为对照组（79例）。收集患者的临床资料，对比两组患者的脂质代谢、糖代谢、肝脏硬度，并检测患者血清FGF21水平和miR-21相对表达量。结果 观察组甘油三酯（TG）和肝脏弹性硬度值（LSM）均高于对照组（P <0.05），高密度脂蛋白（HDL-C）低于对照组（P <0.05）。观察组糖化血红蛋白（HbA1c）和胰岛素抵抗指数（HOMA-IR）均高于对照组（P <0.05），FGF-21水平和miR-21相对均表达量低于对照组（P <0.05）。多因素一般Logistic回归分析，结果显示：TG水平［O^R=3.710（95% CI：1.288，10.688）］、LSM ［O^R=1.657（95% CI：1.188，2.311）］、HbA1c 水平［O^R=1.806（95% CI：1.184，2.754）］、HOMA-IR水平［O^R=8.423（95% CI：2.860，24.804）］均是进展性肝纤维化的危险因素（P <0.05）；HDL-C水平［O^R=0.002（95% CI：0.000，0.042］、FGF-21水平［O^R=0.229（95% CI：0.056，0.940）］和miR-21相对表达量［O^R=0.020（95% CI： 0.000，0.785）］均是进展性肝纤维化的保护因素（P <0.05）。受试者工作特征曲线结果显示，LSM、FGF-21、miR-21联合预测进展性肝纤维化的曲线下面积为0.925（95% CI：0.865，0.988），敏感性为92.6%（95% CI：0.757，0.991），特异性为83.5%（95% CI：0.735，0.914）。结论 NAFLD合并2型糖尿病患者血清FGF-21水平和miR-21相对表达量对病情进展有重要意义，是预测进展性肝纤维化的重要指标。

Abstract:

Objective To investigate the changes and clinical significance of serum levels of fibroblast growth factor 21 (FGF-21) and microRNA-21 (miR-21) in patients with non-alcoholic fatty liver disease (NAFLD) coexisting with type 2 diabetes (T2D).Methods A total of 106 patients with NAFLD and T2D were recruited in our hospital between January 2020 and January 2024. Based on the severity of NAFLD fibrosis, patients were categorized into the observation group (n = 27) with progressive fibrosis, and the control group (n = 79) with non-progressive fibrosis. Clinical data of patients were collected, and lipid and glucose metabolism as well as the liver stiffness were compared between the two groups. Serum FGF-21 levels and relative expression of miR-21 were measured.Results The observation group exhibited higher levels of triglyceride (TG) and liver stiffness measurement (LSM) (P < 0.05), and lower levels of high-density lipoprotein cholesterol (HDL-C) compared with the control group (P < 0.05). The observation group showed higher levels of hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR) (P < 0.05), and lower levels of FGF-21 and miR-21 expression (P < 0.05). The multivariable Logistic regression analysis indicated that high TG levels [O^R = 3.710（95% CI：1.288，10.688) ], LSM [O^R = 1.657（95% CI：1.188，2.311) ], HbA1c levels [O^R = 1.806（95% CI：1.184，2.754) ], and HOMA-IR [O^R = 8.423（95% CI：2.860，24.804) ] were risk factors for progressive fibrosis (P < 0.05), and high HDL-C levels [O^R = 0.002（95% CI：0.000，0.042) ], FGF-21 levels [O^R = 0.229（95% CI：0.056，0.940) ], and miR-21 expression [O^R = 0.020（95% CI： 0.000，0.785) ] were protective factors for progressive liver fibrosis (P < 0.05). The ROC curve analysis showed that the combined detection of LSM, FGF-21, and miR-21 had a diagnostic accuracy of 92.5% (95% CI: 0.865, 0.988) for predicting progressive liver fibrosis, with a sensitivity of 92.6% (95% CI: 0.757, 0.991) and a specificity of 83.5% (95% CI: 0.735, 0.914).Conclusions Serum levels of FGF-21 and miR-21 play a significant role in the progression of NAFLD coexisting with T2D and are important markers for predicting progressive liver fibrosis.