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[Angiotensin II type-1 receptor antagonists and diabetes mellitus]
1I. Medizinische Abteilung, Krankenanstalt Rudolfstiftung, Juchgasse 25, A-1030 Wien. Christoph.Schnack@kar.magwien.gv.at
Insights
Arterial hypertension complicates diabetes, increasing risks. Antihypertensive treatments, including ACE inhibitors and angiotensin II receptor antagonists, show promise in managing diabetic nephropathy and cardiovascular issues.
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
Background:
- Arterial hypertension is a significant risk factor for microangiopathic diabetic complications, increasing cardiovascular morbidity and mortality.
- Intensified antihypertensive treatment, including ACE inhibitors, can reduce these complications in diabetic patients, even normotensive ones, potentially preventing diabetic nephropathy.
- ACE inhibitors increase bradykinin, causing side effects but offering potential intrarenal benefits; novel angiotensin II receptor type 1 antagonists lack bradykinin influence and may be better tolerated.
Purpose of the Study:
- To evaluate the efficacy and tolerability of angiotensin II receptor type 1 antagonists compared to ACE inhibitors in diabetic patients.
- To explore the long-term clinical relevance of intrarenal effects of these drug classes in diabetic nephropathy.
- To assess the impact of angiotensin II receptor type 1 antagonists on glucose and lipid metabolism and urinary albumin excretion rate.
Main Methods:
- Review of existing studies on ACE inhibitors and angiotensin II receptor type 1 antagonists in diabetic patients and animal models.
- Comparison of short-term renal effects, including blood pressure and albumin excretion rate.
- Analysis of data on side effects, metabolic control, and urinary albumin excretion rate (UAER) in specific patient populations.
Main Results:
- Angiotensin II receptor type 1 antagonists are well-tolerated and do not affect metabolic control in diabetic patients.
- Nephroprotective effects in diabetic animal models are comparable between ACE inhibitors and angiotensin II receptor type 1 antagonists.
- Short-term studies show similar reductions in blood pressure and albumin excretion, with Losartane showing more pronounced UAER reduction than Felodipine in Chinese type 2 diabetic patients.
Conclusions:
- Angiotensin II receptor type 1 antagonists offer a well-tolerated treatment option for diabetic patients with potential benefits for microangiopathic complications.
- Further randomized long-term studies are needed to directly compare the long-term efficacy of angiotensin II receptor type 1 antagonists with ACE inhibitors in preventing diabetic nephropathy.
- The potential benefit of combining ACE inhibitors and angiotensin II receptor type 1 antagonists warrants further investigation, as does the influence of ACE gene polymorphisms on therapeutic options.
Abstract:
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.