内分泌代谢病基本用药培训分析.ppt

1、 2型糖尿病不是一种单纯的疾病，它涉及全身多种脏器和组织。它可引起下列多种慢性并发症以及合并症：1.糖尿病视网膜病变，是目前导致适合工作年龄人群失明的首要原因；2.糖尿病肾病，是终末期肾病的首要原因；3.中风，糖尿病可使心血管死亡和中风危险性增加2到4倍；4.心血管疾病，糖尿病患者中每10人最终死于心血管事件；5.糖尿病神经病变：是导致非创伤性下肢截肢手术的首要原因。要实现血糖控制达标，我们首先必须对糖尿病的根本病因有所了解。胰岛素抵抗在组织水平造成的后果包括胰岛素 的 糖 组织和 组织的 。.，在 脏 合并 在对胰岛素 糖 的 增加， 引起 血糖， 导致胰岛素 性 糖尿病的加currency

2、1，胰岛素 因胰“fifl 性。.De Fronzo J. Diabetes 1998; 37:667687.DISCUSSIONBy decreasing beta-cell workload and improving beta-cell response, the incretin glucagon-like peptide 1 (GLP-1) is an important regulator of glucose homeostasisA thorough understanding of the 5 GLP-1 glucoregulatory effects is importan

3、t to assess the value of GLP-1 in controlling glucose levels, particularly during the postprandial period Upon ingestion of food, GLP-1 is secreted in into the bloodstream and enhances glucose dependent insulin secretion from beta-cells GLP-1 suppresses inappropriately elevated glucagon secretion fr

4、om alpha cells Lower levels of glucagon lead to a reduction of glucose output from the liver and indirectly reduce the beta-cell workloadBy slowing the gastric emptying rate, GLP-1 slows the release of nutrients into the gut allowing more time to control the postprandial increase in glucose levelsGL

5、P-1 promotes satiety, potentially through centrally mediated mechanisms BACKGROUNDGLP-1 is secreted from L cells of the small intestineGLP-1 decreases beta-cell workload, hence the demand for insulin secretion, by:Regulating the rate of gastric emptying such that meal nutrients are delivered to the

6、small intestine and, in turn, absorbed into the circulation more smoothly, reducing peak nutrient absorption and insulin demand (beta-cell workload)Decreasing postprandial glucagon secretion from pancreatic alpha cells, which helps to maintain the counterregulatory balance between insulin and glucag

7、on Reducing postprandial glucagon secretion, GLP-1 has an indirect benefit on beta-cell workload, since decreased glucagon secretion will produce decreased postprandial hepatic glucose outputHaving effects on the central nervous system, resulting in increased satiety (sensation of satisfaction with

8、food intake) and a reduction of food intakeEffect on Beta cell: Drucker DJ. Diabetes. 1998;47:159-169.Effect on Alpha cell: Larsson H, et al. Acta Physiol Scand. 1997;160:413-422.Effects on Liver: Larsson H, et al. Acta Physiol Scand. 1997;160:413-422.Effects on Stomach: Nauck MA, et al. Diabetologi

9、a. 1996;39:1546-1553.Effects on CNS: Flint A, et al. J Clin Invest. 1998;101:515-520.Both GLP-1 and glucose-dependent insulinotropic peptide (GIP) are incretins; i.e., gut peptides that are released from the GI tract in response to a meal to potentiate glucose-dependent insulin release.1 The physiol

10、ogic role of incretin hormones in maintaining glycemic control suggests that the incretin axis is a potential target for therapeutic intervention in type 2 diabetes.1 After their release into the circulation, both GLP and GIP are degraded by the enzyme dipeptidyl peptidase IV (DPP-IV).2 Prevention o

11、f the degradation of GLP-1 and GIP to their inactive metabolites via DPP-IV inhibition therefore may represent a rational approach to the treatment of type 2 diabetes.1 对于”作我们 不是非 ，我们现在它要作于 ， 的胰岛素 性， 它 性及 的 。 的 ， 脏和 中 的 ， fl 的胰岛素的抵抗。目前 使的人 胰素 是糖尿病的控制最有的 , 是因先 的 性,使在 有要 的 ,fl 制了它 的.我可以 到 的 線,是正人體的胰素

12、線.fl綠 的則是人 胰素製劑在人體中的作 線.人 胰素製劑:1 因 起始作較慢,所以患者要在餐前30 鐘注射.2 無法在餐後立即達到所的胰素血中濃 , 因 無法達到如正人體般的餐後血糖的控制3 作時間較長,血中濃 無法在餐後立即下 ,所以在餐與餐之間,可會 現 血糖的現象和人 胰素相比,NovoRapid可以更符合正人體的 模 和人 胰素相比,NovoRapid可以更符合正人體的 模 和人 胰素相比,NovoRapid可以更符合正人體的 模 国 多采 量法，MMI初始量30- mg/日（相当于PTU 300-0 mg/日，CMZ 30-0 mg/日；国外为MMI 10-0 mg/日，PTU 100-600 mg/日），临症状缓解后开始 量直至维持量药。由于甲状“ 储 的甲状“激素要2周才耗尽，T的循环半期是7，所以ATD开始发挥作的 间该药后-6周。总疗程在12-18 月，短于12 月复发率增加，长于18 月亦不显著增加缓解率。目前国外许多研究发现采小剂量（10-1 mg/日）疗 大剂量疗疗相 ，且不良 较， 是初始 剂量可使症状较快缓解。欧洲多中心研究发现 剂量MMI（0 mg/日）使起更快， 是 剂量维持在最 要剂量（10 mg/日）是安全的， 缓解率不亚于 剂量，fl且达疗 不良 之间的平衡。