-糖苷酶抑制剂作为试验药物79.ppt

* * * * * Acarbose, through its mechanism of action by inhibiting the a-glucosidases, reduces postprandial rise in plasma glucose and plasma insulin. Its only side-effects are mild to moderate gastrointestinal symptoms such as flatulence and diarrhea, and these usually decrease over time. These can be minimized by a “start low, go slow” dosage policy. As such, alpha-glucosidase inhibitors are safe and non-toxic. * * * Fig. 14.2/1.10A_1400 * * * * * Change in blood pressure and in the number of subjects developing hypertension. The number of subjects developing cardiovascular events. * * * Fig. 14.2/1.10A_1400 * * * The Risk Factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study found that, in non-diabetic patients, intima-media thickness (IMT) increased as the 2-hour post-challenge glucose level increased. 2-hr post-challenge glucose concentrations had a greater influence on IMT than AIC. Additionally, for each value of AIC, an increased level of 2-hour post-challenge glucose was associated with an increase in IMT. This was not true for fasting glucose. For each value of AIC, increasing levels of fasting glucose had no effect on IMT. * * The results of the STOP-NIDDM Trial showed that reducing postprandial PPG with acarbose in subjects with IGT was associated with: a 49% reduction in the incidence of cardiovascular events; and, a 50% reduction in the rate of progression of the CIMT. Professor Hanefeld presented, in subjects with type 2 diabetes: data showing that PPG was a strong predictor of CIMT; a meta-analysis suggesting that acarbose was associated with a 35% reduction in the risk of CVD. * * * * Flow-mediated dilation of brachial artery (%) * * * * ? * Experimental and clinical evidence indicates that both postprandial hyperglycemia is accompanied by oxidative stress, which in turn causes endothelial dysfunction and eventually atherosclerosis. Rapid increases in glucose and lipid levels after ingestion of a meal are also li