2型糖尿病药物治疗的新进展ppt课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,2型糖尿病药物治疗的新进展,南京大学医学院附属鼓楼医院,胡 云,糖尿病的发病率越来越高,2002,年全国营养调查,（,18,岁以上人口）,采用多阶段分层整群随机抽样法，共测定,18,岁以上人群血糖,52416,人，糖尿病诊断参照,1999,年国际糖尿病联盟标准,李立明,等,.,中华流行病学杂志,2005,26:478-484.,我国大城市,20,岁以上人群糖尿病患病率已达,6.37%,2007年6月2008年5月中国20岁以上成年人糖尿病患病率,已达到,9.7%,!,患病率（,%,）,Wenying Yang,NEJM 2010;362:1090-101,中国住院糖尿病患者慢性并发症患病率高,患病率（）,中华医学会糖尿病学分会慢性并发症调查组,.19912000,年全国住院糖尿病患者慢性并发症及相关大血管病变回顾性分析,.,中国医学科学院学报,2002;24:447-51.,2,型糖尿病,1,型糖尿病,中国,2,型糖尿病患者,HbA,1c,达标率,中国糖尿病健康管理调查,2004,华北、华南、华东、华西和东北,5,个地区,49,家市级中心医院,参与分析的患者,2248,例,中国糖尿病健康管理调查,2006,中国,18,个城市,60,家医院登记治疗超过,12,个月的糖尿病患者,参与分析的患者,2702,例,Pan CY.Cur Med Res Opin.2009;25:39-45,潘长玉等,中华内分泌代谢杂志,20:420-424,2004,达标率（,%,）,25.9%,29.5%,44.6%,0,10%,20%,30%,40%,50%,7.5%,达标率（,%,）,26.8%,28.3%,0,10%,20%,30%,40%,50%,6.5%,8%,41.1%,平均,HbA,1c,：,7.6%,平均,HbA,1c,：,7.7%,UKPDS,：糖尿病相关并发症与,HbA,1c,HbA,1c,每降低,1%,危险降低,(,P,.0001),1%,糖尿病,相关死亡,心肌梗死,微血管,并发症,截肢或因为外周,动脉疾病死亡,21%,14%,37%,43%,相对危险,N=3642,UKPDS=United Kingdom Prospective Diabetes Study.,Data adjusted for age,sex,and ethnic group,expressed for white men aged 5054 years at diagnosis and with mean duration of diabetes of 10 years.,Stratton IM et al.UKPDS 35.,BMJ,2000;321:405412.,2型糖尿病的病理生理缺陷,胰高血糖素,（a细胞）,肝脏中葡萄糖产生,肌肉、脂肪摄取葡萄糖,胰岛素抵抗,高血糖,肝脏,胰 腺,脂肪,肌肉,肝脏,胰岛素,（,细胞）,各类药物降糖疗效,干预措施,HbA,1C,下降幅度,(,),磺脲类药物,1.0-2.0,双胍类药物,1.0-2.0,格列酮类药物,0.5-1.4,格列奈类药物,0.5-1.5,-糖苷酶抑制剂,0.5-0.8,胰岛素,不等,GLP-1,0.5-1.0,DPP4,0.5-0.8,Nathan D,Buse J,Davidson M,Ferranini E,Holman R,Sherwin R,and Zinman B.,最新,ADA/EASD 2,型糖尿病管理共识,Online in Diabetes Care 2008;31(12)and Diabetologia October 2008,双胍类：二甲双胍,优点,减少肝脏葡萄糖产生,罕见低血糖,安全性高,体重增加少,对血脂有益,减少大血管并发症,(UKPDS),缺,点,乳酸酸中毒,胃肠道反应达到50%,不耐受达到4%,禁忌症：,肾功能损害,心衰需要药物治疗,缺氧状态,肾功能不全,二甲双胍以原形,由肾脏排泄,二甲双胍,在体内聚集,乳酸性酸中毒,肾功能不全患者禁用二甲双胍,二甲双胍,血清肌酐水平,男性,1.5mg/dL(132.6umol/L),女性,1.4mg/dL(123.8umol/L),肌苷清除率,60ml/min,2,胰岛素增敏剂,通过激活存在于肝脏、肌肉、脂肪组织中的,PPAR,受体来提高胰岛素的敏感性,改善,细胞功能,单药,或联合其他药物,治疗,，,低血糖风险小,对高密度脂蛋白及游离脂肪酸有益,噻唑烷二酮增敏剂类,PPAR,激动剂,基因转录,PPAR,RXR,蛋白合成,mRNA,噻唑烷二酮类,(TZD),的作用机制,增加对胰岛素的反应,增加葡萄糖摄取,降低脂肪酸释放,属于核受体转录因子家族,与,RXR,合成二聚体,调节基因转录以调控脂代谢；与脂肪细胞分化及线粒体产生有关，与糖尿病，肥胖，高血压及炎症有关,噻唑烷二酮类：生物效应,加速脂肪细胞分化,增加游离脂肪酸的摄取及储存；提高皮下脂肪的蓄积,vs.,内脏脂肪,降低甘油三酯水平从而减轻胰岛素抵抗，导致葡萄糖摄取增加（,GLUT1,和,GLUT4,易位）,TNF-,a,表达减少,不增加或轻微增加胰岛素分泌，,胰岛素增敏剂,可能原因,TZD,的不良反应,水钠潴留,水肿患者慎用,心衰,NYHA,分级,和,级密