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*

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。

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

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.