Schnack C, Schernthaner G
I. Medizinische Abteilung, Krankenanstalt Rudolfstiftung, Juchgasse 25, A-1030 Wien.
Wien Med Wochenschr. 2001;151(7-8):165-8.
Arterial hypertension is a major risk factor for microangiopathic diabetic complications and associated with an increased cardiovascular morbidity and mortality. An intensified antihypertensive treatment reduces microangiopathic complications and cardiovascular morbidity and mortality in diabetic patients. Even in normotensive type 1 and type 2 diabetic patients, the treatment with ACE inhibitors may prevent the later development of diabetic nephropathy. Treatment with ACE inhibitors increases the concentrations of bradykinin, which is responsible for the side effects such as cough and urticaria in some patients. On the other hand, bradykinin may have beneficial intrarenal effects decreasing the intraglomerular pressure. The novel angiotensin II receptor type 1 antagonists do not influence the bradykinin concentrations and seem to be tolerated by patients suffering from chronic cough with ACE inhibitor therapy. It is still unclear whether the different intrarenal effects are of clinical relevance in the long-term treatment of diabetic patients. In studies with diabetic animals the nephroprotective effects of ACE inhibitors and angiotensin II type 1 receptor antagonists are comparable. It was shown that glucose and lipid metabolism is not influenced by treatment with angiotensin II type 1 receptor antagonists. Further compared to Felodipine the reduction of urinary albumin excretion rate (UAER) was more pronounced by Losartane in Chinese type 2 diabetic patients. Short-term studies directly comparing the renal effects of ACE inhibitors with AT II type 1 receptor antagonists revealed similar reduction of blood pressure and albumin excretion rate in patients with diabetic nephropathy, so a combination of both substances might be useful. Data from ongoing long-term trials are still missing. Further, it is unknown whether different phenotypes of the ACE gene (DD, II polymorphism) require different therapeutic options. In conclusion, treatment with angiotensin II receptor antagonists is well-tolerated and has no adverse effects on metabolic control in diabetic patients. The beneficial effect on microangiopathic complications however has to be proven in randomized long-term studies in direct comparison with ACE inhibitors, which were clearly shown to delay the development and progression of diabetic nephropathy.
动脉高血压是微血管性糖尿病并发症的主要危险因素，与心血管疾病发病率和死亡率增加相关。强化降压治疗可降低糖尿病患者的微血管并发症以及心血管疾病发病率和死亡率。即使在血压正常的1型和2型糖尿病患者中，使用血管紧张素转换酶（ACE）抑制剂治疗也可预防糖尿病肾病的后期发展。ACE抑制剂治疗会增加缓激肽浓度，而缓激肽是导致部分患者出现咳嗽和荨麻疹等副作用的原因。另一方面，缓激肽可能具有有益的肾内效应，可降低肾小球内压力。新型1型血管紧张素II受体拮抗剂不影响缓激肽浓度，似乎慢性咳嗽患者在接受ACE抑制剂治疗时可耐受。在糖尿病患者的长期治疗中，不同的肾内效应是否具有临床相关性仍不清楚。在糖尿病动物研究中，ACE抑制剂和1型血管紧张素II受体拮抗剂的肾保护作用相当。研究表明，1型血管紧张素II受体拮抗剂治疗不影响糖脂代谢。此外，与非洛地平相比，氯沙坦在中国2型糖尿病患者中更能显著降低尿白蛋白排泄率（UAER）。直接比较ACE抑制剂与1型血管紧张素II受体拮抗剂肾脏效应的短期研究显示，糖尿病肾病患者的血压和白蛋白排泄率降低程度相似，因此两者联合使用可能有效。目前仍缺乏正在进行的长期试验数据。此外，尚不清楚ACE基因的不同表型（DD、II多态性）是否需要不同的治疗方案。总之，血管紧张素II受体拮抗剂治疗耐受性良好，对糖尿病患者的代谢控制无不良影响。然而，其对微血管并发症的有益作用必须在与ACE抑制剂直接比较的随机长期研究中得到证实，ACE抑制剂已明确显示可延缓糖尿病肾病的发生和发展。
