认识及预防糖尿病慢性并发症的技巧之一56课件.ppt

1、mmol/L)中心性肥胖中心性肥胖International Diabetes Federation.International Diabetes Federation.1950 1960 1970 1980 1990 2000 2010医生支持率医生支持率十年期十年期临床首次临床首次使用使用1957糖尿病预防计划糖尿病预防计划（DPP）2002二甲双胍在美国批准上市二甲双胍在美国批准上市1995乳酸性酸中毒乳酸性酸中毒美国停用美国停用苯乙双胍苯乙双胍1978美国美国“大学联合大学联合糖尿病研究计划糖尿病研究计划关于苯乙双胍关于苯乙双胍的研究结果的研究结果 1968糖尿病指南：糖尿病指南：二甲

2、双胍为一线药二甲双胍为一线药2000UKPDS：二甲双胍治疗后二甲双胍治疗后死亡率死亡率/致残率致残率 1998葡萄糖合成葡萄糖合成胰岛素胰岛素糖尿病基因糖尿病基因脂肪因子脂肪因子炎症炎症高血糖高血糖游离脂肪酸游离脂肪酸其它因素其它因素细胞细胞功能障碍功能障碍糖摄取糖摄取脂肪分解脂肪分解胰岛素抵抗胰岛素抵抗脂肪酸脂肪酸血糖血糖Stumvoll et al.Lancet 2005发生率每增加1 HbA1c10203040500所有糖尿病相关性终点事件心肌梗死卒中微血管并发症+21%+37%+12%+14%Chiasson J-L et al.Ann Intern Med 1994;121:928

3、-935Lee AJ.Pharmacotherapy 1996;16:327-351Garber AJ et al.Am J Med 1997;103:491-497Fchtenbusch M et al.Exp Clin Endocrinol Diabetes 2000;108:151-163*与对照组比较的下降值与对照组比较的下降值Hermann.Diabetic Medicine 1994;11:953-960高血糖基础水平的影响高血糖基础水平的影响 1000mg2000mg轻度糖尿病轻度糖尿病空腹血糖空腹血糖(mmol/L)0 周数周数 12160140120100(mg/dl)100

4、0mg2000mg3000mg严重糖尿病严重糖尿病空腹血糖空腹血糖(mmol/L)0 周数周数 12220200180160(mg/dl)二甲双胍二甲双胍二甲双胍二甲双胍678910910111213 06789246810HbA1c(%)随机分组后年数正常上限=6.2%传统治疗传统治疗格列本脲格列本脲氯磺丙脲氯磺丙脲二甲双胍二甲双胍胰岛素胰岛素0UK Prospective Diabetes Study(UKPDS)Group.Lancet 1998;352:854865.12%12%16%16%25%25%21%21%P=0.029P=0.029P=0.052P=0.052P=0.0099

5、P=0.0099P=0.015P=0.015NSNS心血管和全因死亡率心血管和全因死亡率 任一糖尿病终点事件任一糖尿病终点事件心肌梗死心肌梗死微血管并发症微血管并发症1212年时视网膜病年时视网膜病强化策略7.0%HbA1c传统策略7.9%HbA1cvs4209(82%)17042505非超重组非超重组胰岛素或胰岛素或 磺脲类磺脲类n=951二甲双胍二甲双胍n=342传统策略传统策略n=411强化策略强化策略n=1293体重指数体重指数 25-30 46%体重指数体重指数 30 54%UKPDS 34,Lancet 1998;352:854-865.传统治疗(C)强化治疗(I)二甲双胍(M)年

6、数 终点事件患者百分比UKPDS Group Lancet 1998UKPDS Group Lancet 1998糖尿病相关终点事件糖尿病相关终点事件32%32%0.00230.00237%7%NSNS糖尿病相关死亡糖尿病相关死亡 42%42%0.0170.01720%20%NSNS全因死亡全因死亡 36%36%0.0110.0118%8%NSNS心肌梗死心肌梗死 39%39%0.010.0121%21%NSNS中风中风41%41%NSNS14%14%NSNS微血管疾病微血管疾病 29%29%NSNS16%16%NSNS二甲双胍二甲双胍磺脲类磺脲类/胰岛素胰岛素 危险变化危险变化 p p值值

7、危险变化危险变化 p p值值a UKPDS 34 1998;b Stratton&Holman ADA 2003心肌梗死心肌梗死危险性降低危险性降低 39%(致死性致死性/非致死性非致死性)危险性降低危险性降低50%(致死性致死性)危险性下降：危险性下降：血糖下降超过期望值血糖下降超过期望值5倍倍 非剂量依赖性非剂量依赖性:剂量剂量(mg/d)1700 相对危险性相对危险性 0.46 0.54事件患者的百分比传统治疗强化治疗二甲双胍年数临床结果临床结果糖尿病相关死亡糖尿病相关死亡全因死亡全因死亡心肌梗死心肌梗死(致死性致死性/非致死性非致死性)致死性心肌梗死致死性心肌梗死中风中风(致死性致死性

8、/非致死性非致死性)致死性中风致死性中风随访随访(年年)UKPDS磺脲类磺脲类/胰岛素胰岛素n=386710%6%16%6%(+)11%(+)17%10.7UKPDS卡托普利卡托普利阿替洛尔阿替洛尔n=114832%18%21%28%44%58%8.4HOPE雷米普利雷米普利n=357737%24%22%-33%-4.5HOT非洛地平非洛地平阿司匹林阿司匹林n=150167%43%51%-30%-3.84S辛伐他丁辛伐他丁n=20236%43%55%-62%-5.4UKPDS二甲双胍二甲双胍n=75342%36%39%50%41%25%10.7UKPDS Group.Lancet 1998;3

9、52:854-865.血浆胰岛素血浆胰岛素0 2 4 6 8 10磺脲类磺脲类胰岛素胰岛素饮食饮食二甲双胍二甲双胍糖化血红蛋白糖化血红蛋白(HbA1C)二甲双胍二甲双胍磺脲类磺脲类饮食饮食胰岛素胰岛素67890246810随机分组后时间随机分组后时间(年年)中位中位%HbA1C-50-2502550随机分组后时间随机分组后时间(年年)中位变化中位变化(pmol/L)Stumvoll et al.Lancet 2005葡萄糖合成葡萄糖合成胰岛素胰岛素糖摄取糖摄取脂肪分解脂肪分解脂肪酸脂肪酸血糖血糖作用弱主要作用作用弱总胆固醇 低密度脂蛋白胆固醇高密度脂蛋白胆固醇甘油三酯平均变化值%P0.05P0

10、.05P0.05105-5-10-15-200DeFronzo et al.NEJM 1995Nagi DK,Yudkin JS.Diabetes Care.1993;16:621-629.基础对照组二甲双胍PAI-1 活性(U/mL)12周结果35302520151050 HbA1C=1.3%空腹血糖=55 mg/dL*P0.001 与安慰剂比较.Kurukulasuriya R et al.Diabetes.1999;48:A315(Abstract 1399.5).数据为治疗6个月的平均值体重体重(kg)体重指数体重指数(Kg/m2)总脂肪总脂肪(L)总皮下脂肪总皮下脂肪(L)腹部皮下脂

11、肪腹部皮下脂肪(L)内脏脂肪内脏脂肪(L)瘦肌肉组织瘦肌肉组织 与基础比较与基础比较的改变值的改变值-3.3-1.2-2.8-2.1-1.2-0.6 0%下降值下降值 4%4%9%7%11%15%无变化无变化P 0.006 0.006 0.014 0.025 0.0130.01NS3234 例糖耐量异常患者例糖耐量异常患者二甲双胍二甲双胍+生活方式咨询生活方式咨询安慰剂安慰剂+生活方式咨询生活方式咨询强化生活方式咨询强化生活方式咨询双盲双盲公开公开随访随访 3 年年Diabetes Prevention Program Research Group.N Engl J Med 2002;346:

12、393-403RYang Wenying et al.Chin J Endocrinol Metab 2001;17:131-136对照组对照组饮食饮食+运动运动阿卡波糖阿卡波糖 50mg tid二甲双胍二甲双胍 250mg tid糖耐量正常、异常、糖尿病采用糖耐量正常、异常、糖尿病采用1985 WHO诊断标准（诊断标准（75g OGGT）病例病例数数85608888糖耐量糖耐量正常正常%27.728.171.144,4糖耐量糖耐量异常异常%37.447.422.943.2糖尿病糖尿病%34.924.66.012.4年糖尿病年糖尿病发生率发生率11.68.224.1剔除剔除2357 怡开对防治

13、脑动脉硬化，改善脑供血，预防脑血管性痴呆有重要作用。药理实验证实药理实验证实*：结扎沙土鼠双侧颈总动脉造成严重脑缺血脑缺血的情况下，怡开怡开能改善软脑膜微循环，增加能改善软脑膜微循环，增加软脑膜血流量软脑膜血流量；未服怡开怡开的脑缺血组仅为正常对照组的33。为临床防治脑缺血提供了实验依据。参考文献：参考文献：*微循环杂志微循环杂志1997；71：23结扎前结扎后 立即中科院基础医学研究所病生理室 薛全福等更 有 效 更 安 全 更 经 济*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPd

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15、qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMb

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17、%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK

18、8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&

19、s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgPdLaI6F3C0y)v&s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPd

20、MaI7F4C0z)w#oXlTiQfNbK8H5D2A-x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQeMbJ7G4D1z-w*t

21、!qYmVjSgOdLaI6F3B0y)v%s#pXlUiQfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmfNbK8H5D2A+x*u$qZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnVkShPdMaJ7

22、F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$r

23、ZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E+x*u$rZnWkShPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G

24、5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI6F3C0y)v&s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiQfNcK8H5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B+y(v%r#

25、oXlTiQeNbK8G5D2A-!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUjRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E

26、2B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYnVjSgOdLaI6F3C0y%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlT

27、iQfNbK8G5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%VkSgPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x

28、(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI6F3C0y)v&s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#pXlUiQfNcK8H5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPeMaJ7B0y)v%s#pXlUiQfNcK8H5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlUiQfN

29、bK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcG5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfN