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1、从预防低血糖的重要性看DPP4i的应用价值,目录,低血糖风险不容忽视,达标与低血糖矛盾：不可调和还是对立统一？,追溯矛盾的根源，探寻理想治疗方案,DPP4抑制剂在理想降糖治疗中的应用价值,低血糖分类,Seaquist, E.R., et al., Diabetes Care, 2013. 36(5): p. 1384-95. 糖尿病学分会, 中国2型糖尿病防治指南(征求意见稿), 2013.,PG: plasma glucose,低血糖是糖尿病治疗的常见并发症,Ray, K.K., et al., Lancet, 2009. 373(9677): p. 1765-1772.,* These v
2、alues indicate number of events (instead of number of individuals) and values given in parentheses are event rates per 100 person-years; these values were not included in the calculation of the combined proportion Any hypoglycaemic episodes refer to those with symptoms compatible with hypoglycaemia.
3、 Serious episodes are those that required hospital admission Hypoglycaemia defined as blood glucose2.8 mmol/l or the presence of typical signs and symptoms of hypoglycaemia without another apparent cause. Patients with transient dysfunction of the central nervous system, who were unable to treat the
4、mselves, requiring help from another person, were said to have serious hypoglycaemia. Also note that both treatment groups lost weight, expressed as negative weight gain Any episodes are those hypoglycaemic episodes with symptoms, and serious episodes are life threatening, or those that cause hospit
5、alization, disability, death or incapacity Any hypoglycaemic event refers to events requiring any form of assistance. Serious events are those that required medical assistance.,UK Hypoglycaemia Study group. Diabetolgia 2007 50:11401147.,病程长的患者有更高的严重低血糖风险,无症状性低血糖：被低估的风险,Chico A et al. Diabetes Care.
6、2003;26(4):11537. Cryer, P. N Engl J Med 2004;350:2272-2279.,CGMS血糖监测的糖尿病患者中，无症状性低血糖发生率达55.71,Cryer PE. J Clin Invest. 2006:116(6):14701473.,低血糖危害： 反复发作与感知受损的恶性循环,低血糖感知受损,糖尿病患者在过程中可以反复发生低血糖，患者最初出现低血糖时有低血糖症状，但低血糖反复发生后，再出现低血糖时则不再有低血糖症状,低血糖感知受损显著增加重度低血糖发生率,Gold A.E.et al.Diabetes Care, 1994; 17:697-703
7、 Henderson et al. Diabet Med 2003;20(12):101621,重度低血糖定义为需要外界帮助才能恢复的低血糖。参与者根据低血糖感知评分17来记录低血糖症状强度的主观变化，1 = 总能感知到，7= 从未感知到， 评分 4 符合感知受损,重度低血糖*(事件/患者/年),0,T2DM,0.22,2.15,感知正常 (n=144),感知受损 (n=13),升高9倍,重度低血糖*(事件/患者/年),0,0.5,1.0,1.5,2.0,2.5,T1DM,0.48,2.83,感知正常 (n=144),感知受损 (n=13),升高6倍,3.0,0.5,1.0,1.5,2.0,2
8、.5,3.0,发生严重低血糖的患者心血管死亡风险显著增加,Zoungas S, et al. N Engl J Med 2010;363:1410-8.,老年低血糖反应范围的压缩,3.0,3.5,4.0,2.5,动脉血糖（mmol/L）,老年患者,年轻患者,年轻患者,感知低血糖症状,严重低血糖,老年人不仅对低血糖症状感知的阈值下降 而且对严重低血糖耐受性更差,老年患者,Matyka K, et al. Diabetes Care. 1997;20(2):135-41.,提高对低血糖的认知，不要忽视每一次低血糖发作！,低血糖是糖尿病治疗的常见并发症之一 先前的低血糖发作会使机体低血糖防御机制受损
9、，导致反复发生低血糖，反复发生低血糖导致患者对低血糖的感知受损 低血糖感知受损最终增加了重度低血糖的发生，增加心血管风险 老年患者、长病程患者有更高的严重低血糖风险,小结,目录,低血糖风险不容忽视,达标与低血糖矛盾：不可调和还是对立统一？,追溯矛盾的根源，探寻理想治疗方案,DPP4抑制剂在理想降糖治疗中的应用价值,治疗与低血糖的矛盾？,Ray, K.K., et al., Lancet, 2009. 373(9677): p. 1765-1772.,* These values indicate number of events (instead of number of individual
10、s) and values given in parentheses are event rates per 100 person-years; these values were not included in the calculation of the combined proportion Any hypoglycaemic episodes refer to those with symptoms compatible with hypoglycaemia. Serious episodes are those that required hospital admission Hyp
11、oglycaemia defined as blood glucose2.8 mmol/l or the presence of typical signs and symptoms of hypoglycaemia without another apparent cause. Patients with transient dysfunction of the central nervous system, who were unable to treat themselves, requiring help from another person, were said to have s
12、erious hypoglycaemia. Also note that both treatment groups lost weight, expressed as negative weight gain Any episodes are those hypoglycaemic episodes with symptoms, and serious episodes are life threatening, or those that cause hospitalization, disability, death or incapacity Any hypoglycaemic eve
13、nt refers to events requiring any form of assistance. Serious events are those that required medical assistance.,强化血糖控制，增加低血糖事件发生,2013年4月15日，美国糖尿病学会(ADA)和美国内分泌学会(ENDO)对既往与新进证据进行回顾，共同发布关于低血糖和糖尿病的共识,2013 ADA/ENDO发布低血糖共识 特别强调以低血糖预防为主的策略,共识的主要编撰者：Dr Elizabeth R. Seaquist “共识的最重要的方面是：使临床医生可以认识到低血糖是一个切实存在
14、的问题并且会带来极大的危害“,Seaquist, E.R., et al., Diabetes Care, 2013. 36(5): p. 1384-95.,2013年IDF老年糖尿病管理全球指南 血糖控制目标的制定需考虑低血糖风险,在为老年糖尿病患者制定血糖控制目标时，需考虑患者的功能状态、合并症情况(尤其是心血管疾病)，以及低血糖风险和微血管并发症 对于老年糖尿病住院患者，通常 空腹血糖目标为8.0mmol/L(140mg/dl) 餐后血糖目标为10.0mmol/L(180mg/dl) 临终患者血糖监测频率为每天2次到3天1次，血糖控制在9-15mmol/L(160-270 mg/dl)即
15、可,International Diabetes Federation. Managing Older People with Type 2 Diabetes Global Guideline. 2013,2013年IDF发布 老年2型糖尿病管理全球指南,理想的降糖治疗方案,减少低血糖 ,HbA 1c 达标,有效性:,安全性:,小结,强化治疗在有效控制血糖的同时，常常也增加低血糖风险 美国糖尿病协会与内分泌学会发表共识，呼吁临床医生引起对低血糖的重视 2013年IDF老年糖尿病管理全球指南推荐，血糖控制目标的制定需考虑低血糖风险 理想的降糖方案应能达到疗效与安全性的统一,达标与低血糖风险：对立
16、与统一,目录,低血糖风险不容忽视,达标与低血糖矛盾：不可调和还是对立统一？,追溯矛盾的根源，探寻理想治疗方案,DPP4抑制剂在理想降糖治疗中的应用价值,寻找矛盾的根源： 低血糖发生机制和危险因素,低血糖：反调节机制受损(尤其是、细胞功能失调) 内源性胰岛素分泌失调 胰高血糖素反应缺陷 自主神经反应衰竭, 葡萄糖,-细胞数量减少,-细胞肥大 /细胞比例增加,+, 葡萄糖摄取, 肝葡萄糖输出,+,-细胞功能失调,-细胞功能失调,Unger RH. Metabolism. 1974;23:581.,2型糖尿病患者胰岛功能失调,-细胞的反调节机制受损 是导致低血糖风险增加的重要原因,Cryer PE. Endocrinology. 2012;153(3):1039-48.,目录,低血糖风险不容忽视,达标与低血糖矛盾：不可调和还是对立统一？,追溯矛盾的根源，探寻理想治疗方案,
