二甲双胍联合达格列净治疗T2DM合并NAFLD患者疗效及血清二肽基肽酶4和C肽变化*

doi:10.3969/j.issn.1672-5069.2022.03.019

摘要/Abstract

摘要： 目的探讨应用二甲双胍联合达格列净治疗2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者疗效及血清可溶性二肽基肽酶4(sDPP-4)和空腹C肽的变化。方法 2018年9月~2021年9月我院收治的T2DM合并NAFLD患者98例,采用随机数字表法分为对照组49例和观察组49例,分别给予二甲双胍或二甲双胍联合达格列净治疗24 w。检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)。采用电化学发光法检测血清空腹胰岛素(FINS),并计算稳态模型胰岛素抵抗指数(HOMA-IR)。采用化学发光法检测血清空腹C肽,采用ELISA法检测血清sDPP-4。结果在治疗24 w末,观察组血清GGT水平为(61.0±6.4)U/L,显著低于对照组【(79.2±6.9)U/L,P<0.05】;肝/脾CT比值为(0.9±0.2),显著高于对照组【(0.7±0.2),P<0.05】,血清空腹C肽水平为(1.6±0.3)ng/ml,显著低于对照组【(2.2±0.5)ng/ml,P<0.05】,sDPP-4水平为(901.5±228.3)ng/ml,显著低于对照组【(1086.2±275.8)ng/ml,P<0.05】;FPG水平为(6.1±1.2)mmol/L,显著低于对照组【(6.9±1.5)mmol/L,P<0.05】,HbA1c水平为(7.1±1.3)%,显著低于对照组【(7.8±1.0)%,P<0.05】,HOMA-IR水平为(2.3±0.5),显著低于对照组【(2.8±0.4),P<0.05】;血清TC水平为(4.5±0.6)mmol/L,显著低于对照组【(5.1±0.6)mmol/L,P<0.05】,TG水平为(2.2±0.4)mmol/L,显著低于对照组【(2.6±0.5)mmol/L,P<0.05】,LDL-C水平为(3.1±0.4)mmol/L,显著低于对照组【(3.5±0.5)mmol/L,P<0.05】,而血清HDL-C水平为(1.8±0.4)mmol/L,显著高于对照组【(1.4±0.3)mmol/L,P<0.05】。结论应用二甲双胍联合达格列净治疗T2DM合并NAFLD患者能有效控制血糖并纠正脂代谢紊乱,降低血清sDPP-4和胰岛素抵抗水平,在改善肝脂肪变性方面显示出较好的治疗苗头,值得深入探讨。

关键词: 非酒精性脂肪性肝病, 2型糖尿病, 达格列净, 二甲双胍, 可溶性二肽基肽酶4, 胰岛素抵抗, 治疗

Abstract: Objective The aim of this study was to observe the short-term efficacy of metformin and dapagliflozin combination therapy in the treatment of patients with diabetes mellitus type 2 (T2DM) and non-alcoholic fatty liver diseases (NAFLD) and their impact on serum soluble dipeptidyl peptidase 4 (sDPP-4) and C-peptide levels. Methods 98 patients with T2DM and NAFLD were enrolled in our hospital between September 2018 and September 2021, and were divided randomly into control (n=49) and observation (n=49) group, receiving metformin or metformin and dapagliflozin combination therapy, respectively, for 24 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FPG) and glycosylated hemoglobin (HbA1c) were routinely detected. Serum fasting insulin (FINS) was detected by electrochemiluminescence, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Serum fasting C-peptide level was detected by chemiluminescence. Serum sDPP-4 level was detected by ELISA. Results At the end of 24 week treatment, serum GGT level was (61.0±6.4) U/L, significantly lower than [(79.2±6.9) U/L, P<0.05] in the control; the ratio of liver/spleen CT value in the observation group was (0.9±0.2), significantly higher than [(0.7±0.2), P<0.05], serum fasting C-peptide level was (1.6±0.3) ng/ml, significantly lower than [(2.2±0.5) ng/ml, P<0.05], and serum sDPP-4 level was (901.5±228.3) ng/ml, also significantly lower than [(1086.2±275.8) ng/ml, P<0.05] in the control in the control; the FPG level was (6.1±1.2) mmol/L, significantly lower than [(6.9±1.5) mmol/L, P<0.05], the HbA1c level was (7.1±1.3)%, significantly lower than [(7.8±1.0)%, P<0.05], and the HOMA-IR was (2.3±0.5), significantly lower than [(2.8±0.4), P<0.05] in the control; serum TC level was (4.5±0.6) mmol/L, serum TG level was (2.2±0.4) mmol/L, and LDL-C level was (3.1±0.4) mmol/L, all significantly lower than [(5.1±0.6) mmol/L, (2.6±0.5) mmol/L and (3.5±0.5) mmol/L, P<0.05], while serum HDL-C level was (1.8±0.4) mmol/L, significantly higher than [(1.4±0.3) mmol/L, P<0.05] in the control. Conclusion The combination of metformin and dapagliflozin therapy could effectively control blood glucose levels, correct lipid metabolism disorders, and reduce serum sDPP-4 level in patients with T2DM and NAFLD, which might be related to the remission of insulin resistance.

Key words: Non-alcoholic fatty liver diseases, Type 2 diabetes mellitus, Dapagliflozin, Metformin, Soluble dipeptidyl peptidase 4, Insulin resistance, Therapy

王诗淞, 林辉雄, 张泰胜, 董俪雯, 王英霞, 林秋香. 二甲双胍联合达格列净治疗T2DM合并NAFLD患者疗效及血清二肽基肽酶4和C肽变化^*[J]. 实用肝脏病杂志, 2022, 25(3): 379-382.

Wang Shisong, Lin Huixiong, Zhang Taisheng, et al. Short-term observation of metformin and dapagliflozin combination therapy in the treatment of patients with T2DM and NAFLD and their impact on serum dipeptidyl peptidase 4 and C-peptide levels[J]. Journal of Practical Hepatology, 2022, 25(3): 379-382.

参考文献

[1] Schonfels W, Beckmann JH, Ahrens M, et al. Histologic improvement of NAFLD in patients with obesity after bariatric surgery based on standardized NAS (NAFLD activity score). Surg Obes Relat Dis, 2018, 14(10):1607-1616.
[2] Koch LK, Yeh MM. Nonalcoholic fatty liver disease (NAFLD): diagnosis, pitfalls, and staging. Ann Diagn Pathol, 2018, 37(1):83-90.
[3] Eslam M, Valenti L, Romeo S . Genetics and epigenetics of NAFLD and NASH: Clinical impact. J Hepatol, 2018, 28(2):268-279.
[4] Khan RS, Bril F, Cusi K, et al. Modulation of insulin resistance in nonalcoholic fatty liver disease. Hepatology, 2019, 70(2):711-724.
[5] Tilg H, Moschen AR, Roden M. NAFLD and diabetes mellitus. Nat Rev Gastroenterol Hepatol, 2017, 14(1):32-42.
[6] Inoue M, Hayashi A, Taguchi T, et al. Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease. J Diabetes Investig, 2019, 10(4):1004-1011.
[7] Gautam A, Agrawal PK, Doneria J, et al. Effects of canagliflozin on abnormal liver function tests in patients of type 2 diabetes with non-alcoholic fatty liver disease. J Assoc Physicians India, 2018, 66(8):62-66.
[8] Shimizu M, Suzuki K, Kato K, et al. Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obes Metab, 2019, 21(2):285-292.
[9] 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018更新版). 实用肝脏病杂志, 2018, 21(2):177-186.
[10] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版). 中华糖尿病杂志, 2018, 10(1):4-67.
[11] Younossi ZM, Golabi P, Avila L, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepato, 2019, 71(4):793-801.
[12] Bril F. Nonalcoholic fatty liver disease in type 2 diabetes: awareness is the first step toward change. Hepatobiliary Surg Nutr, 2020, 9(4):493-496.
[13]梁小丽, 邝继孙, 刘秋莉, 等. 非诺贝特联合热量限制饮食治疗非酒精性脂肪性肝病合并2型糖尿病患者疗效研究. 实用肝脏病杂志, 2021, 24(1):51-54.
[14] Dougherty JA, Guirguis E, Thornby KA. Asystematic review of newer antidiabetic agents in the treatment of nonalcoholic fatty liver disease. Ann Pharmacother, 2021, 55(1):65-79.
[15] Neuman MG, Cohen LB, Nanau RM. Biomarkers in nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol, 2014, 28(11):607-618.
[16] 陈丽丽, 符茂雄, 蒙绪标,等. 空腹C肽评估NAFLD合并T2DM患者肝纤维化进展价值分析. 实用肝脏病杂志, 2020, 23(1):38-41.
[17] Kleiner DE. Histopathology, grading and staging of nonalcoholic fatty liver disease. Minerva Gastroenterol Dietol, 2017, 64(1):28-38.
[18] Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol, 2015, 62(1):47-64.
[19] Hayashizaki-Someya Y, Kurosaki E, Takasu T, et al. Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient l-amino acid-defined diet in rats. Eur J Pharmacol, 2015, 754(1):19-24.
[20] Honda Y, Imajo K, Kato T, et al. The selective SGLT2 inhibitor ipragliflozin has a therapeutic effect on nonalcoholic steatohepatitis in mice. PLoS One, 2016, 11(1):e0146337.
[21] Ghorpade DS, Ozcan L, Zheng Z, et al. Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature, 2018, 555(7698):673-677.
[22] Aso Y, Kato K, Sakurai S, et al. Impact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease. Int J Clin Pract, 2019, 73(5):e13335.

二甲双胍联合达格列净治疗T2DM合并NAFLD患者疗效及血清二肽基肽酶4和C肽变化^*

Short-term observation of metformin and dapagliflozin combination therapy in the treatment of patients with T2DM and NAFLD and their impact on serum dipeptidyl peptidase 4 and C-peptide levels

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	郭悦承, 陆伦根. 肝纤维化临床诊断与治疗研究进展[J]. 实用肝脏病杂志, 2022, 25(3): 305-308.
[2]	年福临, 鲁晓岚. 糖尿病与非酒精性脂肪性肝病^*[J]. 实用肝脏病杂志, 2022, 25(3): 314-317.
[3]	黄俊榕, 吴昌儒, 吴健林. 恩替卡韦联合甘草酸二铵治疗慢性乙型肝炎患者效果研究^*[J]. 实用肝脏病杂志, 2022, 25(3): 327-330.
[4]	邹东花, 秘建威, 李玉苓, 赵森. 阿德福韦酯分别联合恩替卡韦或替诺福韦治疗rtA181V/T单位点突变的慢性乙型肝炎患者疗效初步研究^*[J]. 实用肝脏病杂志, 2022, 25(3): 331-334.
[5]	柴晓哲, 朱霞峰, 骆成林, 王少峰. 泛基因型与特异基因型DAAs方案精准治疗基因1b型慢性丙型肝炎患者疗效对比分析^*[J]. 实用肝脏病杂志, 2022, 25(3): 355-358.
[6]	胡春霞, 杨娇楠, 张丰晓, 胡敬华. 格卡瑞韦/哌仑他韦治疗基因1b型慢性丙型肝炎患者疗效及安全性分析^*[J]. 实用肝脏病杂志, 2022, 25(3): 359-362.
[7]	陈业京, 陆清平, 顾少颖. 异甘草酸镁与复方甘草酸单胺治疗药物性肝损伤患者疗效比较研究^*[J]. 实用肝脏病杂志, 2022, 25(3): 371-374.
[8]	杨海华, 周聪, 沈国强, 尤晓红, 孟玲. 134例替加环素致药物性肝损伤老年患者临床特征回顾性分析[J]. 实用肝脏病杂志, 2022, 25(3): 375-378.
[9]	蔡冬梅, 吴文娟, 姜亦伦, 居敏昊. CT检测非酒精性脂肪性肝病合并高危冠状动脉斑块患者冠状动脉指标临床意义探讨^*[J]. 实用肝脏病杂志, 2022, 25(3): 383-386.
[10]	沈扬林, 谭可平, 游忠岚, 陈婵, 陆晖, 甘琼萍, 覃国琦, 陆鹏. 血浆置换序贯双重血浆分子吸附系统治疗慢加急性乙型肝炎肝衰竭患者疗效研究^*[J]. 实用肝脏病杂志, 2022, 25(3): 387-390.
[11]	孙亚男, 曾庆环, 刘远志, 张世斌, 李鹏, 武永乐, 丁惠国. 伴有中/重度食管静脉曲张的慢加急性肝衰竭患者预后危险因素分析^*[J]. 实用肝脏病杂志, 2022, 25(3): 391-394.
[12]	詹惠珍, 杜雅钦, 王松姣. 特利加压素联合腹水浓缩回输术治疗肝硬化并发顽固性腹水患者效果研究^*[J]. 实用肝脏病杂志, 2022, 25(3): 395-398.
[13]	郭慧雯, 张峰, 肖江强, 张玮, 张明, 邹晓平, 诸葛宇征. 球囊导管闭塞下逆行性静脉栓塞术治疗胃静脉曲张破裂出血患者疗效分析^*[J]. 实用肝脏病杂志, 2022, 25(3): 407-410.
[14]	邱云, 杨玫, 薛红红. TACE联合超声引导下微波消融治疗特殊部位原发性肝癌患者疗效研究^*[J]. 实用肝脏病杂志, 2022, 25(3): 419-422.
[15]	马虎成, 任昊桢, 汤宁, 王帅, 张玉衡, 施晓雷. 机器人与开腹手术治疗肝内胆管细胞癌患者近期疗效研究^*[J]. 实用肝脏病杂志, 2022, 25(3): 423-426.