钠-葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病合并非酒精性脂肪肝病的研究进展

薛苗苗; 李雪萍; 李亚; 闫娜娜; 许刚柱; 宋梅

doi:10.3969/j.issn.1001-5256.2019.12.037

钠-葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病合并非酒精性脂肪肝病的研究进展

DOI: 10.3969/j.issn.1001-5256.2019.12.037

1. 西安医学院临床医学院
2. 西安医学院第一附属医院内分泌科
3. 西安医学院第一附属医院神经外科
4. 西安医学院护理学院

基金项目:

陕西省软科学研究计划-重点项目(2018KRM170)；西安医学院护理省级重点学科建设项目(16hlxk03)；

详细信息

中图分类号: R575.5;R587.1
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出版历程
- 收稿日期: 2019-07-22
- 出版日期: 2019-12-20

Research advances in sodium-glucose co-transporter 2 inhibitor in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease

Clinical Medical College,Xi'an Medical University

Research funding:

摘要

摘要: 非酒精性脂肪性肝病（NAFLD）是2型糖尿病（T2DM）的常见并发症,可进展为肝硬化甚至相关性肝癌。然而目前尚缺乏有效的药物治疗。钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）作为一种新批准的口服降血糖药,可有效降低血糖。同时,SGLT-2i尚可从改善脂质堆积,改善胰岛素抵抗,抗炎、抗氧化应激,延缓肝纤维化程度,延缓肝细胞癌进展等方面改善NAFLD。同时,可在减轻高糖毒性、减轻体质量、改善肝功能障碍、降低血尿酸等方面对NAFLD起到预防作用。从T2DM合并NAFLD的现状、SGLT-2i的作用机制、SGLT-2i对T2DM合并NAFLD的预防及安全性方面进行了阐述。
- 糖尿病,2型 /
- 非酒精性脂肪性肝病 /
- 钠-葡萄糖协同转运蛋白2抑制剂
Abstract: Nonalcoholic fatty liver disease( NAFLD) is a common complication of type 2 diabetes mellitus( T2 DM) and can progress to liver cirrhosis and even hepatocellular carcinoma,but there are still no effective pharmacotherapies for NAFLD at present. Sodium-glucose co-transporter 2 inhibitor( SGLT-2 i) is a newly approved oral hypoglycemic agent and can effectively reduce blood glucose. Meanwhile,SGLT-2 i can improve NAFLD by improving lipid accumulation and insulin resistance,exerting anti-inflammatory and anti-oxidative stress effects,reducing liver fibrosis degree,and delaying the progression to hepatocellular carcinoma. SGLT-2 i also helps with the prevention of NAFLD by reducing the toxicity of high glucose,body weight,and blood uric acid and improving liver dysfunction. This article reviews the current status of T2 DM with NAFLD,the mechanism of action of SGLT-2 i,the effect of SGLT-2 i in preventing T2 DM with NAFLD,and the safety of SGLT-2 i.
- diabetes mellitus,type 2 /
- nonalcoholic fatty liver disease /
- sodium-glucose co-transporter-2 inhibitor

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参考文献(54)

[1] KAJI K,NISHIMURA N,SEKI K,et al. Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake[J]. Int J Cancer,2018,142(8):1712-1722.

[2] OBARA K,SHIRAKAMI Y,MARUTA A,et al. Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic mice[J]. Oncotarget,2017,8(35):58353-58363.

[3] QIANG S,NAKATSU Y,SENO Y,et al. Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus[J]. Diabetol Metab Syndr,2015,7(1):104.

[4] ANGULO P,GEORGE J,DAY CP,et al. Serum ferritin levels lack diagnostic accuracy for liver fibrosis in patients with nonalcoholic fatty liver disease[J]. Clin Gastroenterol Hepatol,2014,12(7):1163-1169. e1.

[5] 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[J]. Diabetes Obes Metab,2019,21(2):285-292.

[6] DU S,WANG C,JIANG W,et al. The impact of body weight gain on nonalcoholic fatty liver disease and metabolic syndrome during earlier and later adulthood[J]. Diabetes Res Clin Pract,2016,116:183-191.

[7] YOUNOSSI ZM,KOENIG AB,ABDELATIF D,et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology,2016,64(1):73-84.

[8] YOUNOSSI ZM,GOLABI P,DE AVILA L,et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes:A systematic review and meta-analysis[J]. J Hepatol,2019,71(4):793-801.

[9] LIU DH,YAN Y,LIU MX,et al. Type 2 diabetes mellitus and nonalcoholic fatty liver disease[J]. J Chengde Med Coll,2017,34(1):57-59.(in Chinese)刘东慧，颜勇，刘美晓，等．2型糖尿病与非酒精性脂肪性肝病[J]．承德医学院学报，2017,34(1):57-59.

[10] ARMSTRONG MJ,ADAMS LA,CANBAY A,et al. Extrahepatic complications of nonalcoholic fatty liver disease[J]. Hepatology,2016,20(2):387-401.

[11] YOUNOSSI Z,TACKE F,ARRESE M,et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Hepatology,2019,69(6):2672-2682.

[12] Chinese Society of Endocrinology,Chinese Medical Association. Consensus for diagnosis and treatment of nonalcoholic fatty liver diseases and metabolic disorders(2nd Edition)[J].J Clin Hepatol,2018,34(10):2103-2108.(in Chinese)中华医学会内分泌学分会．非酒精性脂肪性肝病与相关代谢紊乱诊疗共识(第二版)[J]．临床肝胆病杂志，2018,34(10):2103-2108.

[13] TACELLI M,CELSA C,MAGRO B,et al. Antidiabetic drugs in NAFLD:The accomplishment of two goals at once?[J].Pharmaceuticals(Basel),2018,11(4):e121.

[14] QIN Y,XIAO XH. Research progress of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes mellitus with non-alcoholic fatty liver[J]. J Clin Pathol Res,2017,37(11):2485-2488.(in Chinese)秦玉，肖新华．钠-葡萄糖共转运蛋白2抑制剂治疗2型糖尿病合并非酒精性脂肪肝的研究进展[J]．临床与病理杂志，2017,37(11):2485-2488.

[15] SCHORK A,SAYNISCH J,VOSSELER A,et al. Effect of SGLT2inhibitors on body composition,fluid status and renin-angiotensin-aldosterone system in type 2 diabetes:A prospective study using bioimpedance spectroscopy[J]. Cardiovasc Diabetol,2019,18(1):46.

[16] RAJ H,DURGIA H,PALUI R,et al. SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus:A systematic review[J]. World J Diabetes,2019,10(2):114-132.

[17] ZHAO Y,XU L,TIAN D,et al. Effects of sodium-glucose co-transporter 2(SGLT2)inhibitors on serum uric acid level:A meta-analysis of randomized controlled trials[J]. Diabetes Obes Metab,2018,20(2):458-462.

[18] STORGAARD H,GLUUD LL,BENNETT C,et al. Benefits and harms of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes:A systematic review and meta-analysis[J]. PLo S One,2016,11(11):e0166125.

[19] MONAMI M,LIISTRO F,SCATENA A,et al. Short and medium-term efficacy of sodium glucose co-transporter-2(SGLT-2)inhibitors:A meta-analysis of randomized clinical trials[J]. Diabetes Obes Metab,2018,20(5):1213-1222.

[20] SZABLEWSKI L. Distribution of glucose transporters in renal diseases[J]. J Biomed Sci,2017,24(1):64.

[21] DENG D,YAN N. GLUT,SGLT,and SWEET:Structural and mechanistic investigations of the glucose transporters[J].Protein Sci,2016,25(3):546-558.

[22] VALLON V,THOMSON SC. Targeting renal glucose reabsorption to treat hyperglycaemia:The pleiotropic effects of SGLT2inhibition[J]. Diabetologia,2017,60(2):215-225.

[23] POULSEN SB,FENTON RA,RIEG T. Sodium-glucose cotransport[J]. Curr Opin Nephrol Hypertens,2015,24(5):463-469.

[24] XU J,HONG AN,LIANG JL. Diagnostic value of blood glucose,blood lipid and glycosylated hemoglobin in middleaged and elderly patients with type 2 diabetes[J]. Clin J Med Offic,2019,47(9):949-951.(in Chinese)徐佳，洪阿娜，梁金莲．血糖、血脂及糖化血红蛋白检测对中老年2型糖尿病患者诊断价值研究[J]．临床军医杂志，2019,47(9):949-951.

[25] YI M,CHEN RP,YANG R,et al. Increased prevalence and risk of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China[J]. Diabet Med,2017,34(4):505-513.

[26] CHEN CX. Prevalence study of non-alcoholic fatty liver disease and epidemiological study on its relation with glycosylated hemoglobin[D]. Suzhou:Soochow University,2017.(in Chinese)陈长喜．非酒精性脂肪肝患病率调查及与糖化血红蛋白关系的流行病学研究[D]．苏州:苏州大学，2017.

[27] ZHANG Q,YU Y,YANG MF,et al. Association between glycosylated hemoglobin and non-alcoholic fatty liver disease in health examination population[J]. J Cent South Univ(Med Sci),2017,42(5):529-535.(in Chinese)张茜，余杨，杨孟凤，等．健康体检人群糖化血红蛋白水平与非酒精性脂肪肝的相关性[J]．中南大学学报(医学版)，2017,42(5):529-535.

[28] PRASETYA IB,HASAN I,WISNU W,et al. Prevalence and profile of fibrosis in diabetic patients with non-alcoholic fatty liver disease and the associated factors[J]. Acta Med Indones,2017,49(2):91-98.

[29] LEONI S,TOVOLI F,NAPOLI L,et al. Current guidelines for the management of non-alcoholic fatty liver disease:A systematic review with comparative analysis[J]. World J Gastroenterol,2018,24(30):3361-3373.

[30] ARASE Y,SHIRAISHI K,ANZAI K,et al. Effect of sodium glucose co-transporter 2 inhibitors on liver fat mass and body composition in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus[J]. Clin Drug Investig,2019,39(7):631-641.

[31] SCHORK A,SAYNISCH J,VOSSELER A,et al. Effect of SGLT2inhibitors on body composition,fluid status and renin-angiotensin-aldosterone system in type 2 diabetes:A prospective study using bioimpedance spectroscopy[J]. Cardiovasc Diabetol,2019,18(1):46.

[32] MANDAL A,BHATTARAI B,KAFLE P,et al. Elevated liver enzymes in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease[J]. Cureus,2018,10(11):e3626.

[33] RAJ H,DURGIA H,PALUI R,et al. SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus:A systematic review[J]. World J Diabetes,2019,10(2):114-132.

[34] DARMAWAN G,HAMIJOYO L,HASAN I. Association between serum uric acid and non-alcoholic fatty liver disease:A Metaanalysis[J]. Acta Med Indones,2017,49(2):136-147.

[35] JARUVONGVANICH V,AHUJA W,WIRUNSAWANYA K,et al.Hyperuricemia is associated with nonalcoholic fatty liver disease activity score in patients with nonalcoholic fatty liver disease:A systematic review and meta-analysis[J]. Eur J Gastroenterol Hepatol,2017,29(9):1031-1035.

[36] ZHOU Y,WEI F,FAN Y. High serum uric acid and risk of nonalcoholic fatty liver disease:A systematic review and meta-analysis[J]. Clin Biochem,2016,49(7-8):636-642.

[37] ZHAO Y,XU L,TIAN D,et al. Effects of sodium-glucose co-transporter 2(SGLT2)inhibitors on serum uric acid level:A meta-analysis of randomized controlled trials[J]. Diabetes Obes Metab,2018,20(2):458-462.

[38] 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[J]. Eur J Pharmacol,2015,754:19-24.

[39] GHORPADE DS,OZCAN L,ZHENG Z,et al. Hepatocytesecreted DPP4 in obesity promotes adipose inflammation and insulin resistance[J]. Nature,2018,555(7698):673-677.

[40] HATTORI S. Empagliflozin decreases remnant-like particle cholesterol in type 2 diabetes patients with insulin resistance[J]. J Diabetes Investig,2018,9(4):870-874.

[41] 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[J]. Int J Clin Pract,2019,73(5):e13335.

[42] CERNEA S,CAHN A,RAZ I. Pharmacological management of nonalcoholic fatty liver disease in type 2 diabetes[J]. Expert Rev Clin Pharmacol,2017,10(5):535-547.

[43] WANG RB,ZHAO YJ,SONG QK,et al. Inhibitory effect of metformin on inflammatory response of Kupffer cells of liver in diabetic mice and its improvement on phagocytic function[J].J Jilin Univ(Med Edit),2019,45(1):39-44,218.(in Chinese)王睿斌，赵艳杰，宋清坤，等．二甲双胍对糖尿病小鼠肝库普弗细胞炎症反应的抑制作用和吞噬功能的改善作用[J]．吉林大学学报(医学版)，2019,45(1):39-44,218.

[44] YANG LN,CAO Y. Research progress in mechanism of inflammation and autophagy and their interaction in insulin resistance[J]. J Jilin Univ(Med Edit),2019,45(3):742-746.(in Chinese)杨丽娜，曹媛．炎症和自噬及其交互作用在胰岛素抵抗中作用机制的研究进展[J]．吉林大学学报(医学版)，2019,45(3):742-746.

[45] KOMIYA C,TSUCHIYA K,SHIBA K,et al. Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction[J]. PLo S One,2016,11(3):e0151511.

[46] QIANG S,NAKATSU Y,SENO Y,et al. Treatment with the SGLT2inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mel itus[J]. Diabetol Metab Syndr,2015,7(1):104.

[47] ANGULO P,GEORGE J,DAY CP,et al. Serum ferritin levels lack diagnostic accuracy for liver fibrosis in patients with nonalcoholic fatty liver disease[J]. Clin Gastroenterol Hepatol,2014,12(7):1163-1169. e1.

[48] 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[J]. Diabetes Obes Metab,2019,21(2):285-292.

[49] FIGUEIREDO IR,ROSE S,FREIRE NB,et al. Use of sodium-glucose cotransporter-2 inhibitors and urinary tract infections in type 2 diabetes patients:A systematic review[J]. Rev Assoc Med Bras(1992),2019,65(2):246-252.

[50] SUI C,CHEN YZ,LAI YW. Effect of ACEI combined with SGLT-2 inhibitor on diabetic nephropathy proteinuria[J]. Clin J Med Offic,2018,46(12):1437-1438,1440.(in Chinese)隋超，陈亚镇，赖贻旺．血管紧张素转化酶抑制剂联合SGLT-2抑制剂治疗糖尿病肾病效果研究[J]．临床军医杂志，2018,46(12):1437-1438,1440.

[51] THEWJITCHAROEN Y,YENSEUNG N,MALIDAENG A,et al.Effectiveness of long-term treatment with SGLT2 inhibitors:Real-world evidence from a specialized diabetes center[J].Diabetol Metab Syndr,2017,9:96.

[52] TANG H,DAI Q,SHI W,et al. SGLT2 inhibitors and risk of cancer in type 2 diabetes:A systematic review and meta-analysis of andomized controlled trials[J]. Diabetologia,2017,60(10):1862-1872.

[53] TANG HL,LI DD,ZHANG JJ,et al. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2(SGLT2)inhibitors on fracture risk among type 2 diabetes patients:A network and cumulative meta-analysis of randomized controlled trials[J]. Diabetes Obes Metab,2016,18(12):1199-1206.

[54] BONORA BM,AVOGARO A,FADINI GP. Sodium-glucose co-transporter-2 inhibitors and diabetic ketoacidosis:An updated review of the literature[J]. Diabetes Obes Metab,2018,20(1):25-33.

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