课件_炎症与胰岛素抵抗及ARB的作用.pptVIP

* Regression to normoalbuminuria ( 20 ?g/min, or 30 mg/day) at the last visit was more frequent in the patients treated with irbesartan 300 mg than in the control (placebo in addition to other nonexcluded antihypertensive therapies) group (34% vs. 21%, respectively, p=0.006).1 1 Parving et al, 2001a. * SLIDE 30 Metabolic changes, diabetes and atherogenesis – possible actions of irbesartan The metabolic syndrome, like the RAAS, is closely associated with atherogenesis.1 Insulin resistance is a cardinal feature of the metabolic syndrome, and may be linked to endothelial dysfunction by a variety of mechanisms. These include disturbances of signalling pathways common to insulin action and NO production, oxidative stress, hyperlipidaemia, and the secretion of hormones and cytokines by adipose tissue.2 There is growing evidence that RAAS overactivity contributes to the development of the metabolic syndrome and diabetes.3,4 One consequence of this is that RAAS-blocking agents, such as ARBs and ACE inhibitors, have consistently been found to reduce the incidence of type 2 diabetes.4 In addition, treating or delaying the progression of insulin resistance may add to the effectiveness of RAAS blockade in treating atherogenesis and preventing its complications. A variety of mechanisms have been proposed to explain how ARBs may enhance insulin function.4 These include: Improved blood flow to the skeletal muscles, thereby increasing peripheral insulin action Improved blood flow to the pancreas, thereby increasing insulin secretion Increasing the efficiency of the insulin signalling cascade Increasing the efficiency of the glucose transporter Promoting the differentiation of adipocytes, which is inhibited by angiotensin II4 Inducing peroxisome proliferator-activated receptor g (PPAR-g) – particularly in adipocytes PPAR-g is a key molecule in insulin resistance: In humans, mutations in PPARg have been reported to cause the full-blown metabolic syndrome.5 PPAR-g agonists have