1、2型糖尿病合并NAFLD的临床管理,从糖尿病专家的角度,如何看待NAFLD?,Joseph M. Pappachan, et al. Endocrine (2014) 45:344353,内分泌疾病,NAFLD,新,主要内容,1,2,3,T2DM合并NAFLD的流行病学,NAFLD与T2DM发病之间的关系,NAFLD与T2DM对疾病预后的相互影响,4,NAFLD的治疗措施,42.6%的T2DM患者有NAFLD,患者比例,n=939,RACHEL M. WILLIAMSON, et al. Diabetes Care 34:11391144, 2011,爱丁堡2型糖尿病研究(ET2DS)中939
2、例年龄61-76岁的T2DM患者,通过肝脏超声评估脂肪肝的情况,grade 0, normal appearance of liver on ultrasound and initially graded as a “normal ultrasound”;grade 1, possible slight increase in echogenicity or slightly impaired visualization of the diaphragm or intrahepatic vessels, or difficulty in grading as a result of a dis
3、eased or absent right kidneyinitially termed an “indeterminate ultrasound”;grade 2, definite increase in echogenicity and/or definite impaired visualization of the intrahepatic vessels and diaphragm, no or little evidence of focal fatty sparing, initially graded as “evidence of mild steatosis on ult
4、rasound”; grade 3, marked increase in echogenicity and/or poor or no visualization of the diaphragm and intrahepatic vessels, with or without focal fatty sparing, initially graded as “evidence of severe steatosis on ultrasound.” Evidence of hepatic cirrhosis was also sought systematically.,NAFLD患者中前
5、驱糖尿病和T2DM患病率高于非NAFLD人群,We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects withoutNAFLD matched for age, sex, and adiposity.,NAFLD患者和非NAFLD人群前驱糖尿病和T2DM患病率,*P 0.001 vs. without NAFLD,CAROLINA ORTIZ-LOPEZ, et al
6、. Diabetes Care 35:873878, 2012,发生率,NAFLD及其严重性与糖尿病发生率有独立的强相关性,NFS:NAFLD纤维化评分,A cross-sectional study was performed in 43,166 apparently healthy Koreans aged 30-59 years, who underwent a health checkup in 2005 and 2006. Of these, 38,291 subjects without diabetes were followed annually or biennially u
7、ntil December 2011 for the cohort study.,Yoosoo Chang , et al. Am J Gastroenterol 2013; 108:18611868,NAFLD及其严重性与T2DM的累积发生率,P -trend 1.6kg会导致肝脏炎症改变或肝门脉区纤维化风险。,Nila Rafiq, et al. SEMINARS IN LIVER DISEASE, 2008;28(4):427-434,改善IR/纠正代谢紊乱药物的专业意见,根据临床需要,可采用相关药物治疗代谢危险因素及其合并症;这些药物对NAFLD患者血清酶谱异常和肝组织学病变的改善作用
8、,尚有待进一步临床试验证实。,均为小样本研究,对二甲双胍报道的疗效不一;目前暂不建议对无糖尿病异常的NAFLD患者常规应用TZD药物治疗。,中华医学会肝病学分会脂肪肝和酒精性肝病学组.胃肠病学和肝病学杂志,2010; 19(6):483-487中华医学会内分泌学分会肝病与代谢学组. 中华内分泌代谢杂志, 2010;26(7): 531-534,2,1,抗炎保肝药物治疗的应用地位,合理选用多烯磷脂酰胆碱、维生素E、水飞蓟素(宾)、S-腺苷蛋氨酸和还原型谷胱甘肽等12种药物作为辅助治疗。,中华医学会内分泌学分会肝病与代谢学组. 中华内分泌代谢杂志, 2010;26(7): 531-534,NAFL
9、D经基础治疗3-6个月仍无效,且伴肝酶增高、MS、2型糖尿病伴NAFLD患者以及肝活体组织检查证实为NASH和病程呈慢性进展性经过者。,T2DM合并NAFLD的综合治疗:PPC+Met vs Met,孙存序,等.临床荟萃.2008.23(17):1272-3.,研究病例选择:邯郸市中心医院2007年3月-12月门诊及住院治疗初诊为T2DM合并NAFLD的患者,n=74,28-60岁治疗组在饮食控制和运动治疗基础上口服二甲双胍500mg,每日3次,多烯磷脂酰胆碱胶囊2粒(456 mg)口服;对照组只在饮食控制和运动治疗的基础上口服二甲双胍500mg,每日3次,总疗程12周,p0.05,临床控制:
10、临床症状消失,血脂正常,超声复查脂肪肝样变消失。显效:症状、体征基本消失,肝脏超声示脂肪肝消失或下降2个级别(如重度转为轻度),血脂恢复正常或基本正常。有效:症状、体征明显改善,肝脏超声示脂肪肝表现明显好转或下降1个级别(如重度转为中度),血脂指标改变率30。无效:症状、体征无改善,肝脏超声示脂肪肝表现无明显变化,血脂指标无明显改善。,T2DM合并NAFLD的综合治疗:PPC+Met vs Met,甘油三酯,孙存序,等.临床荟萃.2008.23(17):1272-3.,研究病例选择:邯郸市中心医院2007年3月-12月门诊及住院治疗初诊为T2DM合并NAFLD的患者,n=74,28-60岁治疗
11、组在饮食控制和运动治疗基础上口服二甲双胍500mg,每日3次,多烯磷脂酰胆碱胶囊2粒(456 mg)口服;对照组只在饮食控制和运动治疗的基础上口服二甲双胍500mg,每日3次,总疗程12周,*,*,* p0.01,6.18,6.19,5.12,5.72,总胆固醇,孙存序,等.临床荟萃.2008.23(17):1272-3.,T2DM合并NAFLD的综合治疗:PPC+Met vs Met,研究病例选择:邯郸市中心医院2007年3月-12月门诊及住院治疗初诊为T2DM合并NAFLD的患者,n=74,28-60岁治疗组在饮食控制和运动治疗基础上口服二甲双胍500mg,每日3次,多烯磷脂酰胆碱胶囊2粒
12、(456 mg)口服;对照组只在饮食控制和运动治疗的基础上口服二甲双胍500mg,每日3次,总疗程12周,*,*,* p0.01,针对NAFLD的治疗药物主要随机临床研究,Natalia Mazzella, et al. Clin Liver Dis 18 (2014) 7389,小 结:NAFLD的治疗,NAFLD的治疗包括调整生活方式、纠正代谢紊乱、合理抗炎保肝等;纠正代谢紊乱方面:目前没有确切的一致性证据证明相关药物的有效性和安全性;临床研究证明,对T2DM合并NAFLD的患者,综合治疗能有效地纠正代谢异常、改善NAFLD病情。针对NAFLD治疗的药物还在进一步研发中。,糖尿病合并NAFLD:未来仍需解决的问题,药物治疗是否独立于生活方式改变而启动?根据年龄、并发症、疾病严重程度的个体化因素,应如何选择治疗药物?对于合并糖尿病的NAFLD患者,应选择哪种调节代谢的药物?在生活方式改变不明显时,是否要终身持续药物治疗?,Natalia Mazzella, et al. Clin Liver Dis 18 (2014) 7389,谢 谢 聆 听 !,