Cooper Mark E, Tikellis Chris, Thomas Merlin C
Danielle Alberti Memorial Centre for Diabetic Complications, Wynn Domain, Baker Heart Research Institute, Melbourne, Victoria, Australia.
J Hypertens Suppl. 2006 Mar;24(1):S57-63. doi: 10.1097/01.hjh.0000220408.91987.eb.
Patients with essential hypertension are at increased risk of type 2 (non-insulin-dependent) diabetes. Recent large studies have been unable to delineate any superiority in one class of antihypertensive drug over another, independent of their effects in reducing blood pressure; however, in the longer term, antihypertensive agents that are able to reduce the risk of diabetes may have a theoretical advantage. To this end, the findings of several recent clinical trials have suggested that blockade of the renin-angiotensin system (RAS) may protect against the development of de-novo diabetes in 'at risk' patients. This beneficial effect appears to outweigh both the adverse metabolic effects of agents used in the control arm of these studies and the control of blood pressure achieved. Furthermore, recent evidence suggests that the RAS may have a direct role in the pathogenesis of diabetes. Angiotensin-mediated increases in oxidative stress, inflammation, and free fatty acids concentrations potentially contribute to beta-cell dysfunction in diabetes. In addition, activation of the RAS appears to potentiate the action of other pathogenic pathways, including glucotoxicity, lipotoxicity, and advanced glycation. In experimental models of type 2 diabetes, blockade of the RAS with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists also results in the improvement of islet structure and function. At least three large controlled trials are currently under way to study the utility of blockade of the RAS in the development of diabetes, including studies of combination therapy. It is hoped that these studies will demonstrate the true potential of blockade of the RAS for the prevention of diabetes.
原发性高血压患者患2型（非胰岛素依赖型）糖尿病的风险增加。最近的大型研究未能明确一类抗高血压药物相对于另一类药物有任何优势，这与它们在降低血压方面的效果无关；然而，从长远来看，能够降低糖尿病风险的抗高血压药物可能具有理论上的优势。为此，最近几项临床试验的结果表明，阻断肾素-血管紧张素系统（RAS）可能预防“高危”患者发生新发糖尿病。这种有益作用似乎超过了这些研究对照组所用药物的不良代谢作用以及所实现的血压控制。此外，最近的证据表明，RAS可能在糖尿病发病机制中起直接作用。血管紧张素介导的氧化应激、炎症和游离脂肪酸浓度增加可能导致糖尿病中的β细胞功能障碍。此外，RAS的激活似乎会增强其他致病途径的作用，包括糖毒性、脂毒性和晚期糖基化。在2型糖尿病实验模型中，用血管紧张素转换酶抑制剂或血管紧张素受体拮抗剂阻断RAS也会导致胰岛结构和功能的改善。目前至少有三项大型对照试验正在进行，以研究阻断RAS在糖尿病发生中的作用，包括联合治疗的研究。希望这些研究将证明阻断RAS预防糖尿病的真正潜力。
