Abbott Kevin C, Bakris George L
Nephrology Service, Walter Reed Army Medical Center, Washington, DC, USA.
Prog Brain Res. 2002;139:289-98. doi: 10.1016/s0079-6123(02)39025-3.
Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.
糖尿病会增加患高血压及相关心血管疾病的风险，这些疾病包括冠状动脉疾病、脑血管疾病、肾脏疾病和外周血管疾病。糖尿病和高血压并存时，发生心血管疾病的风险会增加；事实上，超过1100万美国人同时患有糖尿病和高血压。由于糖尿病发展的主要相关风险因素——肥胖，在全球已达到流行程度，因此在国际上，这些数字还将继续攀升。此外，糖尿病常与血脂异常以及凝血、内皮和代谢异常相关，这也会加重患有这些合并症患者潜在的血管疾病进程。肾素 - 血管紧张素 - 醛固酮系统（RAS）和精氨酸加压素（AVP）在高血压和糖尿病中均过度激活。抑制该系统的药物，如ACE抑制剂以及最近的血管紧张素受体拮抗剂（ARBs），已被证明对糖尿病的微血管和大血管并发症，尤其是肾脏并发症具有有益作用。BRILLIANT研究表明，赖诺普利在降低微量白蛋白尿方面比CCB治疗效果更好。许多其他长期研究证实了ACE抑制剂的这种关联，包括HOPE试验。此外，欧洲赖诺普利治疗胰岛素依赖型糖尿病试验（EUCLID）研究表明，赖诺普利可减缓肾脏疾病的进展，即使是轻度白蛋白尿患者也是如此。事实上，现在有五项规模适当的随机安慰剂对照试验表明，ACE抑制剂和ARBs均可减缓2型糖尿病患者糖尿病肾病的进展。这些效果被证明优于包括二氢吡啶CCB在内的传统降压治疗。在微量白蛋白尿患者中，ACE抑制剂和ARBs可减少微量白蛋白尿进展为蛋白尿的情况，并将进展为蛋白尿的风险降低38%至60%。这很重要，因为已知微量白蛋白尿与血管通透性增加和对血管舒张刺激的反应性降低有关。最近，AVP水平升高与糖尿病中的微量白蛋白尿和超滤有关。将讨论ACE抑制剂、ARBs对糖尿病患者微血管和大血管的益处以及AVP拮抗剂可能发挥的作用，还将给出其临床应用的建议。
