NAFLD与2型糖尿病的关系及其研究进展
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v6i4.8500
Abstract
随着肥胖及2型糖尿病(type 2 diabetes mellitus,T2DM)的流行,非酒精性脂肪性肝病(Non—alcoholic fatty liver disease,NAFLD)的发病率日益剧增,严重威胁人类健康。T2DM会加速NAFLD肝病的进展。反之亦然。NAFLD和糖尿病协同作用,形成恶性循环,导致不良临床事件的发生。尽管NAFLD在T2DM患者中的患病率很高,但在临床工作中常常不被引起重视。本篇综述将重点描述这两种代谢之间因果关系的发病机制及治疗,为临床治疗T2DM合并NAFLD提供理论依据。
Keywords
2型糖尿病；非酒精性脂肪性肝病；发病机制；治疗
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[23] Bluher M.Adipokines–removing road blocks to obesi ty and diabetes therapy.Mol Metab2014;3:230-240.
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[29] Lee CH, Lui DTW,Lam KSL.Adipocyte fatty acid-binding protein,cardiovascular diseases and mortality.Front Immunol2021;12:589206.
[30] Wu X, Shu L,Zhang Z,etal.Adipocyte fatty acid binding protein promotes the onset and progression of liver fibrosis via mediating the crosstalk between liver sinusoidal endoth elial cells and hepatic stellate cells.Adv Sci2021;8:e2003721.
[31] Hedjazifar S,Khatib Shahidi R,Hammarstedt A,etal.The novel adipokine gremlin 1 antagonizes insulin action and is increased in type 2 diabetes and NAFLD/NASH.Diabetes2020;69:331-341.
[32] .Jic C,Flavell RA. Innate sensors of pathogen and stress:linking inflammation to obesity[J].J Allergy Clin Immunol, 2013,132(2) :287-294
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[34] Nagata N., ChenG., Xu L., Ando H. (2022).An update on the chemokine system in the development of NAFLD.Medicina (Kaunas)58(6),761.
[35] Sun Y., Zhu M.,Zhao H., Ni X.,Chang R., Su J., et al..(2020).Serum fibroblast growth factor 19 and total bile acid concentrations are potential biomarkers of hepatocellular carcinoma in patients with type 2 diabetes mellitus.BioMed.Res.Int.2020,1751989.
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[38] Petit JM,Vergès B.Glp-1 receptor agonists in nafld. Diabetes Metab(2017)43Suppl1:2s28-33.
[39] Colosimo S,Ravaioli F,Petroni ML,Brodosi L,Marchignoli F, Barbanti FA, et al..Effects of antidiabetic agents on steatosis and fibrosis biomarkers in type 2 diabetes: A realworld data analysis.Liver Int(2021)41(4):731-42.
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[2] Younossi Z,Tacke F,Arrese M,etal.Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepa titis.Hepatology2019;69:2672-2682.
[3] Chalasani N,Younossi Z,Lavine JE,etal.The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases.Hepatology2018;67:328-357.
[4] Eslam M,Newsome PN,Sarin SK,etal.A new definition for metabolic dysfunction‐associated fatty liver disease: an international expert consensus statement.J Hepatol2020;73: 202-209.
[5] Targher G, Corey KE, Byrne CD, et al The complex link between NAFLD and type 2 diabetes mellitus. Mechanisms and treatments.Nat Rev Gastroenterol Hepatol.2021;18:599-612.
[6] Younossi ZM, Golabi P, de Avila L,etal.The global epidemiology of NAFLD and NASH in patients with type 2 diabetes:a systematic review and meta-analysis.J Hepatol2019; 71:793-801.
[7] Tai FW, Syn WK,Alazawi W.Practical approach to nonalcoholic fatty liver disease in patients with diabetes.Diabet Med2015;32:1121-1133.
[8] Muzica CM, Sfarti C, Trifan A,etal.Nonalcoholic fatty liver disease and type 2 diabetes mellitus: a bidirectional relationship.Can J Gastroenterol Hepatol2020;2020: 6638306.
[9] Younossi ZM,Gramlich T,Matteoni CA,etal.Nonalcoholic fatty liver disease in patients with type 2 diabetes.Clin Gastroenterol Hepatol2004;2:262-265.
[10] Zoppini G, Fedeli U, Gennaro N,etal.Mortality from chronic liver diseases in diabetes.Am J Gastroenterol2014;109: 1020-1025.
[11] Zuo G, Xuan L,Xin Z,etal.New nonalcoholic fatty liver disease and fibrosis progression associate with the risk of incident chronic kidney disease.J Clin Endocrinol Metab2021; 106:e3957-e3968.
[12] 黄珂,石守森,张艳芳.非酒精性脂肪肝病与老年2型糖尿病性微血管病变相关性研究[J].中国老年保健医学,2021,19(6):18-21.
[13] 付冬霞,张云娜,郭宁宁,等.2型糖尿病合并非酒精性脂肪肝患者的临床特征及与慢性并发症的关系研究[J].现代生物医学进展,2017,17(36):7155-7159.
[14] Mantovani AP,Petracca G,Beatrice G,etal.Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501022 adult individuals. Gut 2021; 70:962-969.
[15] Tanase D.M.,Gosav E.M.,Costea C.F.,Ciocoiu M., Lacatusu C.M.,Maranduca M.A.,Ouatu A.,Floria M.The intricate relationsh ip between type 2 diabetes mellitus (T2DM), insulin resistance (IR), and nonalcoholic fatty liver disease (NAFLD)J. DiabetesRes.2020;2020:3920196.doi:10.1155/2020/3920196.
[16] Haemmerle G.,Lass A., Zimmermann R., Gorkiewicz G., Meyer C.,Rozman J., Heldmaier G., Maier R., Theussl C., Eder S., et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase.Science.2006;312:734-737.doi:10.1126/science.1123965.
[17] Samuel V.T.,Shulman G.I.Mechanisms for insulin resis tance:Common threads and missing links.Cell.2012;148:852-871.doi:10.1016/j.cell.2012.02.017.
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[19] Luukkonen P.K.,Qadri S.,Ahlholm N.,Porthan K.,Mannisto V., Sammalkorpi H., Penttila A.K., Hakkarainen A., Lehtimaki T.E., Gaggini M.,etal.Distinct contributions of metabolic dysfunc tion and genetic risk factors in the pathogenesis of nonalcoholic fatty liver disease.J. Hepatol.2022;76:526-535.
[20] Dong Q., Majumdar G., O’Meally R.N., Cole R.N., Elam M.B., Raghow R. Insulin-induced de novo lipid synthesis occurs mainly via mTOR-dependent regulation of proteostasis of SREBP-1c.Mol.Cell.Biochem.2020;463:13-31.
[21] Dewidar B, Kahl S,Pafili K,etal.Metabolic liver disease in diabetes–from mechanisms to clinical trials.Metabolism 2020;111S:154299.
[22] .Tilg H, Adolph TE, Moschen AR.Multiple parallel hitshypothesis in nonalcoholic fatty liver disease: revisited aft er a decade.Hepatology2021;73:833-842.
[23] Bluher M.Adipokines–removing road blocks to obesi ty and diabetes therapy.Mol Metab2014;3:230-240.
[24] Smith GI, Shankaran M, Yoshino M,etal.Insulin resista nce drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.J Clin Investig2020;130:1453-1460.
[25] Hui E,Xu A,Bo Yang H,etal.Obesity as the common soil of non-alcoholic fatty liver disease and diabetes: role of adipokines.J Diabetes Investig2013;4:413-425.
[26] 蔡凤,刘钜荣,范德美,等.TNF-α、白细胞介素等细胞因子在2型糖尿病及非酒精性脂肪性肝病中的作用[J]-《沈阳医学院学报》,2018.2.162-165.
[27] Polyzos SA,Kountouras J,Zavos C,etal.The role ofadip onectin in the pathogenesis and treatment of non- alcohol icfatty liver disease[J].Diabetes Obes Metab,2010,12(5):365- 383.
[28] Makowski L,Boord JB,Maeda K,etal.Lack of macrophage fatty-acid‐binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis.Nat Med 2001;7:699-705.23.Xu A,Tso AWK,Cheung BMY,etal.Circulating adipocyte -fatty acid binding protein levels predict the development of the metabolic syndrome:a 5-year prospective study.Circula tion2007;115:1537-1543.
[29] Lee CH, Lui DTW,Lam KSL.Adipocyte fatty acid-binding protein,cardiovascular diseases and mortality.Front Immunol2021;12:589206.
[30] Wu X, Shu L,Zhang Z,etal.Adipocyte fatty acid binding protein promotes the onset and progression of liver fibrosis via mediating the crosstalk between liver sinusoidal endoth elial cells and hepatic stellate cells.Adv Sci2021;8:e2003721.
[31] Hedjazifar S,Khatib Shahidi R,Hammarstedt A,etal.The novel adipokine gremlin 1 antagonizes insulin action and is increased in type 2 diabetes and NAFLD/NASH.Diabetes2020;69:331-341.
[32] .Jic C,Flavell RA. Innate sensors of pathogen and stress:linking inflammation to obesity[J].J Allergy Clin Immunol, 2013,132(2) :287-294
[33] Lu Y.,Fan C.,Li P.,Lu Y.,Chang X.,Qi K.(2016).Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating G protein-coupled receptors and gut microbiota. Sci.Rep.6,37589.
[34] Nagata N., ChenG., Xu L., Ando H. (2022).An update on the chemokine system in the development of NAFLD.Medicina (Kaunas)58(6),761.
[35] Sun Y., Zhu M.,Zhao H., Ni X.,Chang R., Su J., et al..(2020).Serum fibroblast growth factor 19 and total bile acid concentrations are potential biomarkers of hepatocellular carcinoma in patients with type 2 diabetes mellitus.BioMed.Res.Int.2020,1751989.
[36] Biolato M, Manca F,Marrone G, Cefalo C, Racco S, Migg iano GA, et al..Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease. World J Gastroenterol(2019)25(4):509-20.
[37] Romero-Gómez M,Zelber-Sagi S,Trenell M.Treatment of nafld with diet, physical activity and exercise.J Hepatol (2017)67(4):829-46.
[38] Petit JM,Vergès B.Glp-1 receptor agonists in nafld. Diabetes Metab(2017)43Suppl1:2s28-33.
[39] Colosimo S,Ravaioli F,Petroni ML,Brodosi L,Marchignoli F, Barbanti FA, et al..Effects of antidiabetic agents on steatosis and fibrosis biomarkers in type 2 diabetes: A realworld data analysis.Liver Int(2021)41(4):731-42.
[40] Cusi K,Orsak B,Bril F,Lomonaco R, Hecht J, Ortiz-Lopez C, Tio F, Hardies J, Darland C, Musi N, Webb A, Portillo-Sanchez P.Long-term pioglitazone treatment for patients with nonalc oholic steatohepatitis and prediabetes or type 2 diabetes Mellitus:a randomized trial. Ann Int Med2016;165:305-315.
[41] Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA,Frias JP, Alkhouri N, Bansal MB, Baum S, Neuschwander-Tetri BA,Taub R, Moussa SE.Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind,placebo-controlled,phase 2trial.Lancet2019;394:2012-2024.
[42] Harrison SA, Bashir M,Moussa SE, McCarty K, Pablo Frias J, Taub R, Alkhouri N.Effects of resmetirom on noninvasive endpoints in a 36-week phase 2 active treatment extension study in patients with NASH.Hepatol Commun2021;5:573-588.
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