低血糖对2型糖尿病患者的影响分析.ppt

More Hypoglycemic Events Have Been Reported by Patients Treated With a Sulfonylurea (Glyburide) vs Metformin or a Thiazolidinedione Kahn et al1 conducted A Diabetes Outcome Progression Trial (ADOPT) in patients with recently diagnosed type 2 diabetes who had not received drug treatment. The purpose was to assess the durability of glycemic control with use of a TZD (rosiglitazone; n=1456), a biguanide (metformin; n=1454), or a sulfonylurea (glyburide) (n=1441) as monotherapy for a median of 4 years.1 The results showed that hypoglycemia occurred in 9.8% of patients receiving rosiglitazone, 11.6% of those receiving metformin, and 38.7% of those receiving sulfonylurea (glyburide), as shown in this chart.1 Other studies have also shown an increased frequency of hypoglycemic events in patients with type 2 diabetes treated with a sulfonylurea compared with patients treated with metformin or a TZD.2 Purpose To show how different agents have been associated with the reporting of hypoglycemic events by patients in clinical trials. TakeawayMore hypoglycemic events were reported by patients treated with a sulfonylurea than with metformin or a thiazolidinedione (TZD). References 1. Kahn SE, Haffner SM, Heise MA, et al; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427–2443. 2. Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147(6):386–399. * * 基本的葡萄糖刺激的胰岛素分泌途径包括下列步骤： 葡萄糖通过葡萄糖运输蛋白进入细胞。 葡萄糖代谢引起细胞内三磷酸腺苷 (ATP)升高和细胞内二磷酸腺苷 (ADP)降低，结果是 ATP/ADP比值升高。 ATP/ADP比值升高引起 ATP敏感的钾通道 (K)关闭，引起胞浆膜的去极化。 去极化过程激活电压依赖的钙通道(Ca2+ )，造成Ca2+的内流。 Ca2+的增加刺激胰岛素颗粒的胞吐释放。 背景 一般认为胰高糖素样肽1 (GLP-1)通过调节离子通道的机制（包括ATP敏感的K通道，电压依赖的Ca2+ 通道，电压依赖的K通道和非选择性离子通道）和调节细胞内能量稳态和胞吐作用等机制，增加胰岛素分泌。 讨论 没有葡萄糖的情况下，胰高糖素样肽 1 (GLP-1)信号对胰岛素分泌的作用很小。 GLP-1受体是一种糖蛋白耦合受体，通过环磷酸腺苷 (cAMP)依赖的途径发挥作用，增加细胞内的钙(Ca2+)。 背景 GLP-1对胰岛素分泌的刺激作用是葡萄糖依赖的，需要葡萄糖的浓度正常或升