达格列净对2型糖尿病合并非酒精性脂肪性肝病患者血清FGF-21水平的影响

摘要 目的：分析血清成纤维细胞生长因子-21（FGF-21）与2型糖尿病（T2DM）合并非酒精性脂肪性肝病（NAFLD）患者常见指标及NAFLD纤维化评分（NFS）的相关性，进一步探讨达格列净对T2DM合并NAFLD患者血清FGF-21水平的影响。方法：选取2022年1月至2022年6月徐州医科大学附属徐州市立医院收治的80例T2DM合并NAFLD患者为研究对象（T2DM合并NAFLD组），选择同期80例T2DM不合并NAFLD患者为T2DM组。收集腰围（WC）、身高、体重数据，计算体重指数（BMI）。测定空腹血糖（FPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-c）,低密度脂蛋白胆固醇（LDL-c）、肌酐（Cr）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST ）、白蛋白（Alb）、血小板计数（PLT）等指标，计算胰岛素抵抗指数（HOMA-IR）、NFS。采用酶联免疫吸附（ELISA）法测定FGF-21水平。比较T2DM组和T2DM合并NAFLD组各项指标的差异，探讨血清FGF-21水平与T2DM合并NAFLD患者其他指标的相关性，Logistic回归分析T2DM合并NAFLD的影响因素，受试者工作特征曲线（ROC）分析各影响因素对T2DM合并NAFLD的诊断价值。将80例T2DM合并NAFLD患者按随机数字表法随机分为二甲双胍组和达格列净组各40例，治疗前后观测各项指标变化，并密切监测不良反应。结果：T2DM合并NAFLD组患者WC、BMI、FINS、HbA1c、TG、AST、ALT、HOMA-IR、NFS及FGF-21均高于 T2DM组（P＜0.05）。相关性分析显示，FGF-21水平与T2DM合并NAFLD组患者WC、BMI、HbA1c、TG、HOMA-IR、NFS均存在正相关（P<0.05）。Logistic回归分析显示，BMI、HbA1c、FGF-21、HOMA-IR为影响T2DM患者合并NAFLD的危险因素。ROC曲线分析显示，BMI、HbA1c、FGF-21、HOMA-IR对T2DM合并NAFLD均具有一定预测价值，其中以FGF-21的预测效能最佳。治疗后，达格列净组TG、AST、ALT、NFS、FGF-21水平较二甲双胍组降低更为明显（P＜0.05）。结论：血清FGF-21水平为T2DM合并NAFLD的危险因素，参与了T2DM合并NAFLD发病及进展，且对T2DM合并NAFLD有较好的预测效能。相较于二甲双胍，达格列净可明显降低T2DM合并NAFLD患者血清FGF-21水平并改善NFS，具有一定程度的肝脏保护作用。

Effect of Dapagliflozin on Serum FGF-21 Level in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease

ABSTRACT Objective: To analyze the correlation between serum fibroblast growth factor-21 (FGF-21) and common indicators and NAFLD fibrosis score (NFS) in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD), and to further explore the effect of dapagliflozin on serum FGF-21 level in T2DM patients with NAFLD. Methods: 80 patients with T2DM with NAFLD admitted to Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University from January 2022 to June 2022 were selected as the study subjects (T2DM with NAFLD group), and 80 T2DM patients without NAFLD during the same period were selected as the T2DM group. Collected waist circumference (WC), height, and weight data, and calculate body mass index (BMI). Fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), platelet count (PLT) and other indicators were measured, Calculated HOMA insulin resistance index (HOMA-IR) and NFS. FGF-21 levels were measured using enzyme-linked immunosorbent assay (ELISA). Compare the differences in various indicators between the T2DM group and the T2DM with NAFLD group, explored the correlation between serum FGF-21 levels and other indicators in patients with T2DM with NAFLD, analyzed the influencing factors of T2DM with NAFLD through Logistic regression, and analyzed the diagnostic value of each influencing factor on NAFLD through receiver operating characteristic curve (ROC) analysis. 80 patients with T2DM with NAFLD were randomly divided into metformin group and dapagliflozin group using a random number table method, with 40 patients in each group. Changes in various indicators were observed before and after treatment, and adverse reactions were closely monitored. Results: The WC, BMI, FINS, HbA1c, TG, AST, ALT, HOMA-IR, NFS, and FGF-21 levels in patients with T2DM combined with NAFLD were higher than those in the T2DM group(P<0.05). Correlation analysis showed that the level of FGF-21 was positively correlated with WC, BMI, HbA1c, TG, HOMA-IR, and NFS in patients with T2DM with NAFLD (P<0.05). Logistic regression analysis showed that BMI, HbA1c, FGF-21, and HOMA-IR were risk factors for T2DM patients with NAFLD. ROC curve analysis shows that BMI, HbA1c, FGF-21, and HOMA-IR have certain predictive value for T2DM with NAFLD, with FGF-21 having the best predictive performance. After treatment, the levels of TG, AST, ALT, NFS, and FGF-21 in the dapagliflozin group were significantly lower than those in the metformin group (P<0.05). Conclusion: The serum FGF-21 level is a risk factor for T2DM with NAFLD, and is involved in the onset and progression of T2DM with NAFLD, and has good predictive power for T2DM with NAFLD.Compared to metformin, dapagliflozin can significantly reduce serum FGF-21 levels and improve NFS in T2DM patients with NAFLD, exhibiting a certain degree of liver protection.