达格列净联合二甲双胍治疗T2DM合并NAFLD患者糖脂代谢和自主神经功能变化研究*

doi:10.3969/j.issn.1672-5069.2026.03.009

摘要/Abstract

摘要： 目的探讨达格列净联合二甲双胍治疗2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者糖脂代谢和自主神经功能变化。方法 2023年3月~ 2025年3月我院诊治的T2DM合并NAFLD患者105例,被随机分为对照组52例和观察组53例,分别给予二甲双胍或达格列净联合二甲双胍治疗观察24周。常规检测血清糖脂代谢指标,采用电化学发光法检测血清空腹胰岛素(FINS),计算稳态模型胰岛素抵抗指数(HOMA-IR)。使用内脏脂肪检测仪测量内脏脂肪面积,常规行CT扫描,计算肝脾CT比值,使用24 h心电图检测仪监测正常窦性RR间期的标准差(SDNN)、每5分钟正常RR间期均值的标准差(SDANN)、正常连续RR间期差值的均方根(rMSSD)、相邻RR间期差值超过50毫秒的百分比(pNN50)、低频段功率(LF)和高频段功率(HF)。结果在治疗24周末,观察组内脏脂肪面积为(126.6±15.8)cm²,显著小于对照组【(135.8±17.0)cm²,P<0.05】,而肝/脾CT比值为(0.9±0.2),显著大于对照组【(0.8±0.2)cm²,P<0.05】;观察组HbA1c、FPG和HOMA-IR水平分别为(7.0±0.9)%、(6.0±0.8)mmol/L和(2.2±0.3),均显著低于对照组【分别为(7.7±1.0)%、(6.8±0.9)mmol/L和(2.7±0.3),P<0.05】;观察组SDNN、SDANN、rMSSD、pNN50、LF和HF分别为(111.2±13.9)ms、(106.9±13.4)ms、(21.9±4.7)ms、(4.2±0.9)%、(801.5±100.2)ms²和(494.8±91.9)ms²,均显著高于对照组【分别为(98.1±12.3)ms、(89.3±11.2)ms、(19.5±4.4)ms、(3.7±0.8)%、(724.9±90.6)ms²和(415.6±82.0)ms²,P<0.05】。结论应用达格列净联合二甲双胍治疗T2DM合并NAFLD患者可改善糖代谢指标,降低内脏脂肪,改善自主神经功能。

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, 自主神经功能, 治疗

Abstract: Objective The aim of this study was to investigate dapagliflozin and metformin combination therapy in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Methods A total of 105 patients with T2DM and NAFLD were encountered in our hospital between March 2023 and March 2025, and were randomly assigned to receive metformin in 52 cases for control, or take oral dapagliflozin and metformin in 53 cases for 24 weeks. Serum fasting insulin (FINS) was detected by electrochemiluminescence, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The area of visceral fat was measured by visceral fat detector. The densities of liver and spleen were detected by CT scanner, and liver to spleen CT ratio was calculated. The heart rate variability indexes, e.g., standard deviation of NN intervals (SDNN), standard deviation of the average NN intervals (SDANN), root mean square of successive differences (rMSSD), percent of NN50 in the total number of NN intervals (pNN50), low frequency (LF) and high frequency (HF) were monitored by 24 h electrocardiogram. Results By end of 24-week treatment, visceral fat area in combination group was(126.6±15.8)cm², much less than [(135.8±17.0)cm²,P<0.05],while liver/spleen CT ratio was (0.9±0.2),much greater than [(0.8±0.2)cm²,P<0.05] in the control; HbA1c, FPG and HOMA-IR were (7.0±0.9)%, (6.0±0.8)mmol/L and (2.2±0.3), all significantly lower than [(7.7±1.0)%, (6.8±0.9)mmol/L and (2.7±0.3), respectively, P<0.05] in the control; SDNN, SDANN, rMSSD, pNN50, LF and HF were (111.2±13.9)ms, (106.9±13.4)ms, (21.9±4.7)ms, (4.2±0.9)%, (801.5±100.2)ms² and (494.8±91.9)ms²,all much higher than [(98.1±12.3)ms, (89.3±11.2)ms, (19.5±4.4)ms, (3.7±0.8)%, (724.9±90.6)ms² and (415.6±82.0)ms², respectively, P<0.05] in the control group. Conclusion Combination of dapagliflozin and metformin in treatment of patients with T2DM and NAFLD could significantly improve glucose metabolism, reduce visceral fat, and improve autonomic nerve functions.

Key words: Non-alcoholic fatty liver disease, Type 2 diabetes mellitus, Dapagliflozin, Metformin, Autonomic nerve functions, Therapy

安盟盟, 张芳, 李辉, 刘建凤, 张于, 安向莲, 关平. 达格列净联合二甲双胍治疗T2DM合并NAFLD患者糖脂代谢和自主神经功能变化研究^*[J]. 实用肝脏病杂志, 2026, 29(3): 353-356.

An Mengmeng, Zhang Fang, Li Hui, et al. Improvement of autonomic nerve functions by dapagliflozin and metformin combination therapy in patients with T2DM and NAFLD[J]. Journal of Practical Hepatology, 2026, 29(3): 353-356.

参考文献

[1] Wong ND, Sattar N. Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention. Nat Rev Cardiol,2023,20(10):685-695.
[2] Gupta S, Dominguez M, Golestaneh L. Diabetic kidney disease: an update. Med Clin North Am,2023,107(4):689-705.
[3] 倪文婧,李婕,南月敏.非酒精性脂肪性肝病合并糖尿病的综合管理:2024年美国糖尿病学会指南解读.中华肝脏病杂志,2024,32(6):504-507.
[4] Isaacs S. Nonalcoholic fatty liver disease. Endocrinol Metab Clin North Am,2023,52(1):149-164.
[5] 徐玲玲,卢远,郑燕钗,等. 二甲双胍联合双环醇治疗非酒精性脂肪性肝炎患者短期疗效研究. 实用肝脏病杂志,2025,28(3):358-361.
[6] Nicholson MK, Ghazal Asswad R, Wilding JP. Dapagliflozin for the treatment of type 2 diabetes mellitus - an update. Expert Opin Pharmacother,2021,22(17):2303-2310.
[7] Lundqvist MH, Pereira MJ, Wiklund U,et al. Autonomic nervous system responses to hypo- and hyperglycemia in type 2 diabetes and prediabetes. Eur J Endocrinol,2024,191(5):499-508.
[8] Tao S, Yu L, Li J, Wu J,et al. Insulin resistance quantified by estimated glucose disposal rate predicts cardiovascular disease incidence: a nationwide prospective cohort study. Cardiovasc Diabetol,2025,24(1):161.
[9] 王诗淞,林辉雄,张泰胜,等. 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. 实用肝脏病杂志,2022,25(3):379-382.
[10] Balcıolu AS, Çelik E, Şahin M,et al. Dapagliflozin improves cardiac autonomic function measures in type 2 diabetic patients with cardiac autonomic neuropathy. Anatol J Cardiol,2022,26(11):832-840.
[11] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版). 中华糖尿病杂志,2021,13(4):315-409.
[12] 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年更新版). 实用肝脏病杂志,2018,21(2):177-186.
[13] En Li Cho E, Ang CZ, Quek J,et al. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Gut,2023,72(11):2138-2148.
[14] Makri E, Goulas A, Polyzos SA. Epidemiology, pathogenesis, diagnosis and emerging treatment of nonalcoholic fatty liver disease. Arch Med Res,2021,52(1):25-37.
[15] Kim KS, Hong S, Han K,et al. Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study. BMJ,2024,384:76388.
[16] Dougherty JA, Guirguis E, Thornby KA. A systematic review of newer antidiabetic agents in the treatment of nonalcoholic fatty liver disease. Ann Pharmacother,2021,55(1):65-79.
[17] Caussy C, Aubin A, Loomba R. The relationship between type 2 diabetes, NAFLD, and cardiovascular risk. Curr Diab Rep,2021,21(5):15.
[18] Kamran SH, Ahmad M, Ishtiaq S,et al. Metabolite profiling and biochemical investigation of the antidiabetic potential of Loranthus pulverulentus Wall n-butanol fraction in diabetic animal models. J Ethnopharmacol,2024,318(1):116963.
[19] Yang L, Liu D, Yan H,et al. Dapagliflozin attenuates cholesterol overloading-induced injury in mice hepatocytes with type 2 diabetes mellitus (T2DM) via eliminating oxidative damages. Cell Cycle,2022,21(6):641-654.
[20] Bica IC, Stoica RA, Salmen T,et al. The Effects of sodium-glucose cotransporter 2-inhibitors on steatosis and fibrosis in patients with non-alcoholic fatty liver disease or steatohepatitis and type 2 diabetes: a systematic review of randomized controlled trials. Medicina (Kaunas),2023,59(6):1136.
[21] Tamborlane WV, Laffel LM, Shehadeh N,et al. Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study. Lancet Diabetes Endocrinol,2022,10(5):341-350.

达格列净联合二甲双胍治疗T2DM合并NAFLD患者糖脂代谢和自主神经功能变化研究^*

Improvement of autonomic nerve functions by dapagliflozin and metformin combination therapy in patients with T2DM and NAFLD

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