topic型糖尿病合并nafld的临床管理ppt课件

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例

2、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 ul

4、trasound”; 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 unt

7、il 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 0.001,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,脂质沉积与肝胰岛素敏感度降低有关,IHTG：肝甘油三酯；VF：腹部脂肪,Melania Gaggini, et al. Nutrients 2013, 5, 1544-1

8、560,肝胰岛素敏感性,肝胰岛素抵抗指数,14例正常糖耐量患者和43例T2DM患者，使用核磁共振光谱和核磁共振成像评估内源性糖生成的情况,新,肝脂质沉积与胰岛素抵抗的线性关系,肝胰岛素抵抗,肝胰岛素清除率,14例正常糖耐量患者和43例T2DM患者，使用核磁共振光谱和核磁共振成像评估内源性糖生成的情况,Melania Gaggini, et al. Nutrients 2013, 5, 1544-1560,新,发生胰岛素抵抗时，肝脏能量代谢改变,在肥胖和脂肪变性阶段，肝脏提高氧化活性以获得暂时性适应,发生NASH和DM时(胰岛素抵抗)，肝线粒体功能进行性下降,Chrysi Koliaki , M

9、ichael Roden. Molecular and Cellular Endocrinology 379 (2013) 3542,新,从某种意义上说，脂质沉积的肝细胞也是脂肪细胞，参与胰岛素抵抗的发生,Toshinari Takamura, et al. Endocrine Journal 2012, 59 (9), 745-763,新,ALT是新发T2DM的独立预测因素,We examined the association of serum alanine aminotransferase (ALT) with features of the metabolic syndrome an

10、d whether it predicted incident diabetes independently of routinely measured factors in 5,974 men,血ALT水平与新发糖尿病发生率的关系,Naveed Sattar, et al. Diabetes 53:28552860, 2004,新,肝酶升高与糖尿病前期和T2DM发生有关,The Bogalusa Heart Study： In this retrospective cohort study, normoglycemic(n=874), prediabetic (n= 101), and di

11、abetic (n= 80) adults aged 2650 years (average age 41.3 years) were followed over an average period of 16 years since their young adulthood (aged 1838 years, average age 25.1 years), with measurements of cardiometabolic risk factor variables including ALT and GGT,QUOC MANH NGUYEN, et al. Diabetes Ca

12、re 34:26032607, 2011,ALT and GGT values by quartiles were ,13.0 UI/L and,10 UI/L for quartile 1; from 13 to 18 UI/L and 10 to 14 UI/L for quartile 2; from19 to 28 UI/L and 15 to 22 UI/L for quartile 3; and from 29 to 126 UI/L and 23 to 476 UI/L for quartile 4,新,NAFLD预测T2DM：中国的临床研究数据,The population-b

13、ased cohort study held in Xian, Northwestern China, was based on China National Diabetes and Metabolic Disorders Survey. During a follow-up of 5 years, 508 healthy subjects were included as study sample. NAFLD was determined by abdominal ultrasonography. T2DM and pre-diabetes were diagnosed based on

14、 oral glucose tolerance test,Jie Ming, et al. Liver Int 2015 Apr,新,为什么NAFLD可预测T2DM,研究指出：脂肪肝与进展为2型糖尿病的风险强关联 NAFLD是代谢综合征患者的典型肝脏表现； 肝功能不全模型强烈支持：肝病可继发胰岛素抵抗、细胞功能障碍、糖耐量异常、糖尿病； T2DM的发生可能与肝脂肪浸润具有强相关性,Guido Lattuada, et al. Curr Diab Rep (2011) 11:167172,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T2

15、DM对疾病预后的相互影响,4,NAFLD的治疗措施,NAFLD可能与DM患者多种并发症发生有关,Nathalie C Leite, et al. World J Gastroenterol 2014 July 14; 20(26): 8377-8392,NAFLD 可能与糖尿病患者微血管和大血管并发症发生相关； 在1,2型糖尿病患者中，NAFLD与微量白蛋白尿、肾小球滤过率降低、视网膜病的发生率高有关； T2DM合并NAFLD的患者，慢性肾病的发生率高，独立于其他危险因素之外； 1,2型糖尿病合并NAFLD较无NAFLD患者，亚临床动脉粥样硬化指标如颈动脉内膜中层厚度、动脉硬度增加，临床心血管

16、疾病发生率增加,对于T2DM患者，伴NAFLD的CVD患病率增加,Targher G,et al. Diabetes Med.2006;23(4):403-9,伴NAFLD的2型糖尿病病人心脑血管事件的患病率 显著高于不伴有NAFLD的病人,从门诊2型糖尿病病人中选取400例伴NAFLD和400例不伴NAFLD的病人，年龄及性别随机选择配对，进行心血管疾病评估,伴严重脂肪肝的T2DM患者10年生存率低于不伴严重脂肪肝的患者,H. Perazzo, et al. Aliment Pharmacol Ther. Accepted 13 August 2014,T2DM患者的10年生存率,NAFLD

17、增加T2DM和CVD发病风险的可能机制,Quentin M. Anstee, et al. Rev. Gastroenterol. Hepatol. advance online publication 19 March 2013,反之，动物实验提示T2DM促进NAFLD向纤维化发展,胶原纤维 Azan染色,SMA 染色,蛋氨酸和胆碱缺乏（MCD）饮食造模的NAFLD大鼠：LETO鼠和OLETF鼠（肥胖的T2DM鼠）， -SMA：-平滑肌收缩蛋白，是肝星状细胞激活的标志,Toshinari Takamura, et al. Endocrine Journal 2012, 59 (9), 745

18、-763,胰岛素抵抗和糖尿病加速NAFLD动物模型的病理发展。代表性的显微照片显示了MCD饮食、MCD+高脂饮食和MCD饮食+吡格列酮治疗8周时对OLETF和LETO大鼠的影响。插图中可以看到肝细胞气球样变，箭头显示-SMA阳性星状细胞浸润,肥胖的T2DM大鼠的脂肪性肝炎的进展性更高，吡格列酮可减轻OLETF大鼠中MCD饮食诱导的脂肪性肝炎,T2DM显著提高NAFLD患者肝硬化和死亡风险,ZOBAIR M. YOUNOSSI, et al. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2004;2:262265,NAFLD患者中伴2型糖尿病病人肝硬化和死亡

19、的发生率 显著高于不伴有2型糖尿病的病人,P=0.04,P=0.001,A cohort of patients with NAFLD was identified(n=132), Clinical, pathological, and mortality data were available for this cohort. Patients were categorized and compared according to the presence or absence of T2DM,糖尿病可能是HCC的独立危险因素,Olivier Rosmorduc. Annales dEndoc

20、rinologie 74 (2013) 115120,病例对照研究中， 糖尿病相关的肝癌相对风险,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,以改善脂肪肝为目的的T2DM治疗策略,糖尿病的治疗应前移至肝脏脂肪沉积阶段： 降低肝脏脂肪含量 降低T2DM的发生率 降低T2DM的并发症发生率,NAFLD治疗应是一个综合防治的过程,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,积极处理肝硬化的并发症,健康宣传教育，改变生活方式,

21、控制体质量，减少腰围,改善IR， 纠正代谢紊乱,减少附加打击以免加重肝脏损害,保肝抗炎药物防治肝炎和纤维化,1,2,3,4,5,6,调整饮食和生活方式,中等程度的热量限制,肥胖成人每日热量摄入需减少20924184 kJ (5001000千卡),改变饮食组分，低糖低脂的平衡膳食，减少含蔗糖饮料以及饱和脂肪和反式脂肪的摄入并增加膳食纤维含量,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,体育锻炼,中等量有氧运动，每周4次以上，累计锻炼时间至少150 min；1 每个患者都应计算每天的体育锻炼量，每个患者都应有一个标准；2 无论锻炼是否可

22、以减重，但都可以提高心肺健康，改善胰岛素抵抗及肝酶异常。2,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 意大利肝病学会非酒精性脂肪性肝病诊疗指南（2010,减轻体重的方法和速度,减轻体重的速度： 早期研究显示，每周体重下降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

23、组织学病变的改善作用,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

24、-534,NAFLD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：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