利拉鲁肽对2型糖尿病合并非酒精性脂肪肝患者的影响及机制探究

目的：利拉鲁肽对2型糖尿病（T2DM）合并非酒精性脂肪肝（NAFLD）患者用药后各指标的影响，以及探讨利拉鲁肽的用药机制。方法：入选T2DM合并NAFLD患者80例，按随机数字表法分为A组（40例）：给予二甲双胍联合利拉鲁肽治疗24周。B组（40例）：口服二甲双胍联合促泌剂和/或α-糖苷酶抑制剂治疗。观察治疗24周前后2组患者体质量、腰围、血糖、血脂、HOMA-IR、脂肪肝指数（FLI）及FGF-21等的变化，分析利拉鲁肽对T2DM合并NAFLD的FLI及FGF-21的影响。结果：利拉鲁肽治疗24周后，BMI、WC、FBG、HbA1c、HOMA-IR、TG、TC、LDL、FLI及FGF-21较治疗前明显下降（P<0.05），△FBG、△HbA1c、△TG、△HOMA-IR、△FLI，A组明显高于B组（P<0.05）；FLI和HOMA-IR是影响血清FGF-21的独立危险因素，回归方程为：Y_FGF-21=10.396+2.371×X_HOMA-IR+0.971×X_FLI（R²=0.6，F=38.94，P<0.05）。结论：利拉鲁肽可显著降低T2DM合并NAFLD患者的FLI和FGF-21，利拉鲁肽改善NAFLD与减轻FGF-21抵抗的用药机制可能和胰岛素抵抗有关。

Effect of liraglutide on type 2 diabetes combines with nonalcoholic fatty liver disease and mechanism research

OBJECTIVE To evaluate the effect of liraglutide on various parameters in patients with type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD) after treatment, and to explore the mechanism of liraglutide. METHODS Eighty patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease were enrolled. They were randomly divided into two groups. In group A (40 cases), metformin combined liraglutide was given for 24 weeks. In group B (40 cases), metformin combined with gastrin and/or alpha-glucosidase inhibitors was administered for 24 weeks. The changes of body weight, waist circumference, blood glucose, blood lipids, HOMA-IR, fatty liver index (FLI) and FGF-21 were observed in the two groups before and after treatment for 24 weeks. The effects of liraglutide on FLI and FGF-21 in T2DM combined with NAFLD were analyzed. RESULTS After 24 weeks of treatment with liraglutide, BMI, WC, FBG, HbA1c, HOMA-IR, TG, TC, LDL, FLI and FGF-21 were significantly decreased compared with those before treatment (P<0.05). △FBG, △HbA1c, △TG, △HOMA-IR, △FLI in group A were significantly higher than those in group B (P<0.05). FLI and HOMA-IR were independent risk factors for serum FGF-21. The regression equation was:Y_FGF-21=10.396+2.371×X_HOMA-IR+0.971×X_FLI (R²=0.6,F=38.94,P<0.05). CONCLUSION Liraglutide can significantly reduce FLI and FGF-21 in patients with T2DM and NAFLD. The mechanism of liraglutide improving NAFLD and reducing FGF-21 resistance may be related to insulin resistance.