进阶-0糖尿病的口服药物_20120712摘要.ppt

* One theoretical concern associated with insulin secretagogue therapy is the potential for beta-cell burnout. UKPDS 16 was reported after 6 years of follow-up and showed that intensive therapy was more effective in maintaining FPG and HbA1c levels than conventional therapy. However, the FPG increased progressively with all therapies (P0.0001) and beta-cell function declined regardless of treatment choice. A decline in insulin sensitivity was not observed. Overall, oral sulfonylurea therapy resulted in an initial improvement in beta-cell function. The subsequent decline in beta-cell function with diabetes disease progression was the same for all therapies: metformin, diet, or sulfonylureas. Sulfonylurea (chlorpropamide and glyburide) therapy did not accelerate the decline in beta-cell function. Notably, beta-cell function was already decreased by approximately 50% at the time of diagnosis. Beta-cell function and insulin sensitivity were estimated by HOMA (Homeostasis Model Assessment), a model utilizing the measured fasting insulin and glucose levels of each person. Because the pathogenesis of type 2 diabetes includes both deficiency in insulin secretion and insulin resistance, it is important for therapy to be directed toward both mechanisms. Therapy with an insulin sensitizer or biguanide may be added to an insulin secretagogue to address different mechanisms of pathogenesis. UK Prospective Diabetes Study Group. Overview of 6 years’ therapy of type II diabetes: a progressive disease (UKPDS 16). Diabetes. 1995;44:1249-1258. * UKPDS49研究表明，长期治疗9年后，采用磺脲类降糖药治疗的患者A1C达到7％的患者比例，磺脲类要高于二甲双胍，表明随着β细胞功能的衰退，促泌剂对血糖的长期控制非常重要； * * 在健康人，进餐后胰岛素出现快速的增高，使得餐后血糖在正常范围之内，而在2型糖尿病患者，由于第一时相的缺失，餐后血糖出现了异常的增高。 早相胰岛素分泌高峰对维持摄食后葡萄糖水平稳定起关键作用。T2DM期间可出现代偿性胰岛素分泌增多，以恢复“正常”葡萄糖水平。但患者将会经过一段较长的高血糖和高胰岛素血症期。 有高胰岛素血症者更容易发生糖耐量异常、肥胖、高血压和以甘油三酯水平升高和高密度脂蛋白胆固醇水平降低为特征的血脂异常。所有这些变化均增加罹患冠心病的危险。 在预防血糖急性高峰、长期的高胰岛素血症、高血糖以及相关并发症方面，胰岛素早相分泌是重要的。因此，恢复早相的胰岛素分泌有益于改善总体的血糖控制以及预防疾病进展。 葡萄糖刺激的早相胰岛素分泌受损是2型糖尿病患者胰岛β细胞功能减低的早期标志。 * 瑞格列奈