李 岩,韩彦渊

代谢相关脂肪性肝病（MAFLD）与2型糖尿病（T2DM）发病率逐年上升，二者同为代谢性疾病，相互影响，2型糖尿病（T2DM）是代谢相关脂肪性肝病（MAFLD）的重要危险因素。本文拟综述介绍MAFLD在T2DM中患病率、二者关系以及降糖药治疗MAFLD及肝纤维化的研究进展。

代谢相关脂肪性肝病；患病率；治疗

[1] Eslam,M.,Newsome,P.N.,Sarin,S.K.,Anstee,Q.M.,Targher,G.,Romero-Gomez,M.,Zelber-Sagi,S.,Wai-SunWong,V.,Dufour,J.F.,Schatten-berg,J.M., Kawaguchi,T.,Arrese,M., Valenti,L.,Shiha,G., Tiribelli, C.,Yki-Järvinen,H.,Fan,J.G.,Grønbæk,H.,Yilmaz,Y.,Cortez-Pinto,H.,…George,J.(2020).A new definition for metabolic dysfunction-associated fatty liver disease:An international expert consensus statement.Journal of hepatology,73(1),202-209. [2] Angulo,P.,Kleiner,D.E.,Dam-Larsen,S.,Adams,L.A.,Bjornsson,E.S.,Charatcharoenwitthaya,P.,Mills,P.R.,Keach,J.C.,Lafferty,H.D.,Stahler,A.,Haflidadottir,S.,&Bendtsen,F.(2015).Liver Fibrosis,but No Other Histologic Features,Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease.Gastroenterology,149(2),389-97.e10. [3] Usman,M.,&Bakhtawar,N.(2020).Vitamin E as an Adjuvant Treatment for Non-alcoholic Fatty Liver Disease in Adults:A Systematic Review of Randomized Controlled Trials.Cureus,12(7),e9018. [4] Ahmed,E.S.,Mohamed,H.E.,&Farrag,M.A.(2022).Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway.International journal of immunopathology and pharmacology,36,3946320221137435. [5] Riazi,K.,Azhari,H.,Charette,J.H.,Underwood,F.E.,King,J.A.,Afshar,E.E.,Swain,M.G.,Congly,S.E.,Kaplan,G.G.,&Shaheen,A.A.(2022).The prevalence and incidence of NAFLD worldwide:a systematic review and meta-analysis.The lancet.Gastroenterology&hepatology,7(9),851-861. [6] Younossi,Z.M.,Golabi,P.,de Avila,L.,Paik,J.M.,Srishord,M.,Fukui,N.,Qiu,Y.,Burns,L.,Afendy,A.,&Nader,F.(2019).The global epidemiology of NAFLD and NASH in patients with type 2 diabetes:A systematic review and meta-analysis.Journal of hepatology,71(4),793-801. [7] Powell,E.E.,Wong,V.W.,&Rinella,M.(2021).Non-alcoholic fatty liver disease.Lancet(London,England),397(10290),2212-2224. [8] Diaconu,C.T.,&Guja,C.(2022).Nonalcoholic Fatty Liver Disease and Its Complex Relation with Type 2 Diabetes Mellitus-From Prevalence to Diagnostic Approach and Treatment Strategies.Journal of clinical medicine,11(17),5144. [9] Gaggini,M.,Morelli,M.,Buzzigoli,E.,DeFronzo,R.A.,Bugianesi,E.,&Gastaldelli,A.(2013).Non-alcoholic fatty liver disease(NAFLD)and its connection with insulin resistance,dyslipidemia, atherosclerosis and coronary heart disease.Nutrients,5(5),1544-1560. [10] Baffy,G.,Brunt,E.M.,&Caldwell,S.H.(2012).Hepatocellular carcinoma in non-alcoholic fatty liver disease:an emerging menace.Journal of hepatology,56(6),1384-1391. [11] Cusi K.(2012).Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis:pathophysiology and clinical implications.Gastroenterology,142(4),711-725.e6. [12] DeFronzo R.A.(2010).Insulin resistance,lipotoxicity,type 2 diabetes and atherosclerosis:the missing links.The Claude Bernard Lecture 2009.Diabetologia,53(7),1270-1287. [13] Rabøl,R.,Petersen,K.F.,Dufour,S.,Flannery,C.,&Shulman,G.I.(2011).Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals.Proceedings of the National Academy of Sciences of the United States of America,108(33),13705-13709. [14] Utzschneider,K.M.,Kahn,S.E.,&Polidori,D.C.(2019).Hepatic Insulin Extraction in NAFLD Is Related to Insulin Resistance Rather Than Liver Fat Content.The Journal of clinical endocrinology and metabolism,104(5),1855-1865. [15] Mantovani,A.,Petracca,G.,Beatrice,G.,Tilg,H.,Byrne,C.D.,&Targher,G.(2021).Non-alcoholic fatty liver disease and risk of incident diabetes mellitus:an updated meta-analysis of 501 022 adult individuals.Gut,70(5),962-969. [16] Mantovani,A.,Dalbeni,A.,Beatrice,G.,Cappelli,D.,&Gomez-Peralta,F.(2022).Non-Alcoholic Fatty Liver Disease and Risk of Macro-and Microvascular Complications in Patients with Type 2 Diabetes.Journal of clinical medicine,11(4),968. [17] Zhang,X.,Yip,T.C.,Tse,Y.K.,Hui,V.W.,Li,G.,Lin,H.,Liang,L.Y.,Lai,J.C.,Chan,H.L.,Chan,S.L.,Kong,A.P.,Wong,G.L.,&Wong,V.W.(2023).Duration of type 2 diabetes and liver-related events in nonalcoholic fatty liver disease:A landmark analysis.Hepatology(Baltimore,Md.),78(6),1816-1827. [18] DeFronzo R.A.(2010).Insulin resistance,lipotoxicity,type 2 diabetes and atherosclerosis:the missing links.The Claude Bernard Lecture 2009.Diabetologia,53(7),1270-1287. [19] Buse,J.B.,Wexler,D.J.,Tsapas,A.,Rossing,P.,Mingrone,G.,Mathieu,C.,D'Alessio,D.A.,&Davies,M.J.(2020).2019Update to:Management of Hyperglycemia in Type 2 Diabetes,2018.A Consensus Report by the American Diabetes Association(ADA)and the European Association for the Study of Diabetes(EASD).Diabetes care,43(2),487-493. [20] He,L.,Sabet,A.,Djedjos,S.,Miller,R.,Sun,X.,Hussain,M.A.,Radovick,S.,&Wondisford,F.E.(2009).Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein.Cell,137(4),635-646. [21] Mantovani,A.,Byrne,C.D.,Scorletti,E.,Mantzoros,C.S.,&Targher,G.(2020).Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes:An updated systematic review of randomized controlled trials.Diabetes&metabolism,46(6),427-441. [22] Associazione Italiana per lo Studio del Fegato(AISF),SocietàItaliana di Diabetologia(SID)and SocietàItaliana dell'Obesità(SIO),Members of the guidelines panel,Coordinator,AISF Members,SID Members,SIO Members,&Metodologists(2022).Non-alcoholic fatty liver disease in adults 2021:A clinical practice guideline of the Italian Association for the Study of the Liver(AISF),the Italian Society of Diabetology(SID)and the Italian Society of Obesity(SIO).Digestive and liver disease:official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver,54(2),170-182. [23] Gimeno,R.E.,Briere,D.A.,&Seeley,R.J.(2020).Leveraging the Gut to Treat Metabolic Disease.Cell metabolism,31(4),679-698. [24] J.-M.Petit,B.Vergès,GLP-1 receptor agonists in NAFLD,Diabetes&Metabolism,Volume 43,Supplement 1,2017,Pages 2S28-2S33,ISSN 1262-3636. [25] Armstrong MJ,Gaunt P,Aithal GP,Barton D,Hull D,Parker R,et al..Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis(Lean):A multicentre,doubleblind,randomised, placebocontrolled phase 2 study.Lancet(London England)(2016)387(10019):679-90. [26] Newsome PN,Buchholtz K,Cusi K,Linder M,Okanoue T,Ratziu V,et al..A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.New Engl J Med(2021)384(12):1113-24. [27] Cusi K,Sattar N,García-Pérez LE,Pavo I,Yu M,Robertson KE,et al..Dulaglutide decreases plasma aminotransferases in people with type 2 diabetes in a pattern consistent with liver fat reduction:A Post hoc analysis of the award programme.Diabetic Med J Br Diabetic Assoc(2018)35(10):1434-9. [28] Kuchay MS,Krishan S,Mishra SK,Choudhary NS,Singh MK,Wasir JS,et al..Effect of dulaglutide on liver fat in patients with type 2 diabetes and nafld:Randomised controlled trial(D-lift trial).Diabetologia(2020)63(11):2434-45. [29] Kuchay,M.S.,Farooqui,K.J.,Mishra,S.K.,&Mithal,A.(2021).Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors.Advances in experimental medicine and biology,1307,213-230. [30] Latva-Rasku A,Honka MJ,Kullberg J,Mononen N,Lehtimäki T,Saltevo J,et al..The Sglt2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity:A randomized, double-blind,placebo-controlled study with 8-week treatment in type 2 diabetes patients.Diabetes Care(2019)42(5):931-7. [31] Eriksson JW,Lundkvist P,Jansson PA,Johansson L,Kvarnström M,Moris L,et al..Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes:A double-blind randomised placebo-controlled study.Diabetologia(2018)61(9):1923-34. [32] Shimizu M,Suzuki K,Kato K,Jojima T,Iijima T,Murohisa T,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):285-92. [33] Tobita H,Yazaki T,Kataoka M,Kotani S,Oka A,Mishiro T,et al..Comparison of dapagliflozin and teneligliptin in nonalcoholic fatty liver disease patients without type 2 diabetes mellitus:A prospective randomized study.J Clin Biochem Nutr(2021)68(2):173-80. [34] European Association for the Study of the Liver(EASL)European Association for the Study of Diabetes(EASD)European Association for the Study of Obesity(EASO).Easl-Easd-Easo clinical practice guidelines for the management of non-alcoholic fatty liver disease.J Hepatol(2016)64(6):1388-402. [35] Chalasani N,Younossi Z,Lavine JE,Charlton M,Cusi K,Rinella M,et al..The diagnosis and management of nonalcoholic fatty liver disease:Practice guidance from the American association for the study of liver diseases.Hepatology(2018)67(1):328-57. [36] Cusi K.A diabetologist's perspective of non-alcoholic steatohepatitis(Nash):Knowledge gaps and future directions.Liver Int(2020)40 Suppl 1:82-8. [37] Sanyal AJ,Chalasani N,Kowdley KV,McCullough A,Diehl AM,Bass NM,et al..Pioglitazone,vitamin e,or placebo for nonalcoholic steatohepatitis.New Engl J Med(2010)362(18):1675-85. [38] Aithal GP,Thomas JA,Kaye PV,Lawson A,Ryder SD,Spendlove I,et al..Randomized,placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis.Gastroenterology(2008)135(4):1176-84. [39] Musso,G.,Cassader,M.,Paschetta,E.,&Gambino,R.(2017).Thiazolidinediones and Advanced Liver Fibrosis in Nonalcoholic Steatohe-patitis:A Meta-analysis.JAMA internal medicine,177(5),633-640. [40] Iwasaki,T.,Yoneda,M.,Inamori,M.,Shirakawa,J.,Higurashi,T.,Maeda,S.,Terauchi,Y.,&Nakajima,A.(2011).Sitagliptin as a novel treatment agent for non-alcoholic Fatty liver disease patients with type 2 diabetes mellitus.Hepato-gastroenterology,58(112),2103-2105. [41] Yilmaz,Y.,Yonal,O.,Deyneli,O.,Celikel,C.A.,Kalayci,C.,&Duman,D.G.(2012).Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis.Acta gastro-enterologica Belgica,75(2),240-244. [42] Smits,M.M.,Tonneijck,L.,Muskiet,M.H.,Kramer,M.H.,Pouwels,P.J.,Pieters-van den Bos,I.C.,Hoekstra,T.,Diamant,M.,van Raalte,D.H.,&Cahen,D.L.(2016).Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes:a randomised placebocon-trolled trial.Diabetologia,59(12),2588-2593.

点击下载PDF