低血糖对2型糖尿病患者的影响

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,1,低血糖及其对,2,型糖尿病患者的影响,北京同仁医院内分泌科,杨毅,2,内容,低血糖的定义及其症状,2,型糖尿病患者中低血糖的发病率,低血糖是,2,型糖尿病患者通过充分的血糖控制后达到阳性结果的障碍,基于肠促胰岛激素的治疗方法为充分控制血糖并降低低血糖风险提供新选择,3,美国糖尿病学会对低血糖的定义,低血糖有如下症状特征,血糖水平低,神经低血糖症状和,/,或神经症状,摄入碳水化合物后症状缓解,所有具有潜在危害的异常低血糖都称之为低血糖症,对于使用促胰岛素分泌剂或胰岛素治疗的患者，血糖水平,3.9 mmol/L(,70mg/dL),为低血糖,American Diabetes Association.,Diabetes Care.,2005;28(5):12451249.,4,低血糖的症状,神经症状,1,2,神经低血糖症状,1,2,肾上腺素能症状,心悸,震颤,焦虑,/,觉醒,类胆碱样症状,出汗,饥饿感,感觉异常,认知障碍,行为改变,精神运动异常,抽搐,昏迷,1,型和,2,型糖尿病控制不佳，,1,型糖尿病血糖的严格控制以及老龄是影响血糖阈值的因素,2,3,1.,Cryer PE.,J Clin Invest,.2007;117(4):868870.,2.,Cryer PE.,Diabetes Care,.2003;26(6):19021912.,3.,Meneilly GS et al.,J Clin Endocrinol Metab,.1994;78(6):13411348.,5,5,低血糖的发病率,1993-2005,年间因低血糖急诊,a,的总人数达,5,百万,1,25%,的患者入院,72%,的患者第一诊断为低血糖,其中大约,44%,的病例发生于,65,岁以上的老人,老年患者不容易出现症状性低血糖,2,a,患者为,1,、,2,型糖尿病,.ICD-9,诊断编码,:251.0(,低血糖昏迷,),251.1(,其他指定的低血糖,),251.2(,低血糖,非特定,),270.3(,亮氨酸诱导的低血糖,),775.0(,糖尿病母亲出生婴儿低血糖,),and 775.6(,新生儿低血糖,).ICD-9,编码,250.8,还包括,(,有其他特定表现的糖尿病,),但除以下联合诊断编码以外,:259.8,272.7,681.xx,682.xx,686.9x,707.xx,709.3,730.0,730.2,和,731.8.,1.Ginde AA et al.,Diabetes Care.,2008;31:511,513.,2.,Matyka K et al.,Diabetes Care,.1997;20(2):135,141.,6,2,型糖尿病患者低血糖症状的发病率,1.,Reproduced with permission of Springer Verlag.Lundkvist J et al.,Eur J Health Econom,.2005;6(3):197202.Permission conveyed through Copyright Clearance Center,Inc.,2.,Asia RECAP-DM Study Group.7th IDF Western Pacific Region Congress,Wellington,New Zealand.Poster No.P45.,3.,lvarez Guisasola F et al.,Diabetes Obes Metab,.,2008;10(suppl 1):2532.,自发报告发生,低血糖事件的患者,%,亚洲和欧洲其他研究中,应用口服制剂治疗,2,型糖尿病的患者自发报告低血糖的发生率结果相似,2,3,任何胰岛素,(n=133),仅用口服制剂,(n=176),所有患者,(N=309),0,10,20,30,40,50,60,最近,1,月内低血糖症状的发生率,1,7,1,型和,2,型糖尿病的低血糖发病率与病程相关,1.,Reproduced with permission of Springer Verlag.UK Hypoglycemia Study Group.,Diabetologia,.2007;50(6):11401147.Permission conveyed through Copyright Clearance Center,Inc.,2.,NIDDK 2007.Available at http:/diabetes.niddk.nih.gov/dm/pubs/statistics/.Accessed December 12,2008.,(n=46),(n=54),(n=103),(n=85),(n=75),由于,2,型糖尿病患者占所有诊断为成人糖尿病的,90%95%,2,，故低血糖事件在,2,型糖尿病患者中发生的绝对数比,1,型糖尿病患者更多。,至少,发生,1,次严重低血糖的比例,1,0.0,0.2,0.4,0.6,0.8,1.0,磺脲类治疗,5,年胰岛素治疗,15,年胰岛素治疗,2,型糖尿病,1,型糖尿病,8,2,型糖尿病低血糖的危害,2,型糖尿病患者发生低血糖与使用胰岛素和磺酰脲类药物有关,1,严重低血糖容易引起临床重视，但轻到中度低血糖可能是无症状的并且可能会被漏报,2,3,即使是无症状的低血糖也对患者有危害,4,老年患者比年轻患者发生低血糖相关事件的几率更高,5,1.,Asian-Pacific Type 2 Diabetes Policy Group.4th Edition.2005;158.,2.,Chico A et al.,Diabetes Care.,2003;26(4):11531157.,3.,Canadian Diabetes Association Clinical Practice Guidelines Expert Committee.,Can J Diabetes,.2008;32(suppl 1):S62S64.,4.,California Healthcare Foundation.,J Am Ger Soc.,2003;51(5,suppl):S265S280.,5.,Matyka K et al.,Diabetes Care.,1997;20(2):135141.,9,无症状性低血糖可能被漏报,在连续血糖监控的糖尿病人中，超过,50%,出现过无症状性低血糖,(,未识别出,),1,其他研究者也有类似发现,2,3,1.,Copyright 2003 American Diabetes Association.,Chico A et al.,Diabetes Care.,2003;26(4):11531157.Reprinted with permission from the,American Diabetes Association.,2.,Weber KK et al.,Exp Clin Endocrinol Diabetes,.2007;115(8):491494.,3.,Zick R et al.,Diab Technol Ther,.2007;9(6):483492.,0,25,50,75,100,所有糖尿病患者,1,型糖尿病,患者,患者比例,%,2,型糖尿病,患者,55.7,62.5,46.6,发生,1,次未识别的低血糖事件的患者,%,n=70,n=40,n=30,10,严重低血糖的影响和并发症,血糖水平,10,20,30,40,50,60,70,80,90,100,110,1,2,3,4,5,6,mg/dL,mmol/L,1.,Landstedt-Hallin L et al.,J Intern Med,.1999;246:299307.,2.,Cryer PE.,J Clin Invest,.2007;117(4):868870.,增加心律失常风险,1,进行性神经低血糖症,2,延长心脏复极化,QTc,和,QTd,猝死,认知受损,行为异常,抽搐,昏迷,脑死亡,11,严重并持续的低血糖增加死亡率,葡萄糖为大脑的代谢功能所必需,1,由于大脑自己不能合成葡萄糖，脑组织需要依靠糖循环提供能量,1,当动脉中葡萄糖水平下降,血液到大脑的葡萄糖传输将变慢，从而使脑组织的代谢受限，甚至脑死亡,1,低血糖导致,6%-10%,的,1,型糖尿病患者死亡,2,3,致命性的低血糖并不仅限于,1,型糖尿病,4,致命的磺酰脲类相关性低血糖也有报道,.,5,1.,Cryer PE et al.,Diabetes Care,.2003;26(6):19021912.,2.,DCCT/EDIC Study Research Group.,N Engl J Med,.2007;356:18421852.,3.,Skrivarhaug T et al.,Diabetologia,.2006;49:298305.,4.,Cryer PE.,J Clin Invest,.2006;116(6):14701473.,5.,Shorr RI et al.,Arch Intern Med,.1997;157:16811686.,12,严重的低血糖可能导致,2,型糖尿病患者,QT,间期延长,P,=NS,P,=0.0003,NS=,无显著差异,.13,名联用胰岛素和格列本脲的,2,型糖尿病患者参与低血糖钳夹试验,;,有,8,名参加了正常血糖试验,.,目的是为了在至少,60,分钟的试验中得到稳定的低血糖,2.5 and 3.0 mmol/L,(45 and 54 mg/dL).,Landstedt-Hallin L et al.,J Intern Med,.1999;246:299307.,正常血糖钳夹,(n=8),低血糖钳夹,(n=13),低血糖钳夹后,QT,间期显著延长,增加心律失常风险,0,360,370,380,390,400,410,420,430,440,450,平均,QT,间期,ms,基线,(t=0),钳夹后,(t=150 min),13,CGMS,以及,Holter,监测异常,总发生,胸痛,/,绞痛,的发作,ECG,发生,异常,低血糖,54,10,a,6,a,有症状,26,10,a,4,a,无症状,28,2,血糖正常无快速变化,N/A,0,0,高血糖,59,1,0,血糖快速变化,(100 mg/dL,/,h),50,9,a,2,a,P,0.01,与血糖量正常和高血糖相比,.,胸痛和,ECG,异常的发生率增加可能与低血糖有关,a,参与试验的,2,型糖尿病患者,(n=19;