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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renal community is faced with an ever increasing number of patients reaching end-stage renal failure. Clinical studies have provided clear evidence that angiotensin-converting enzyme (ACE) inhibitors, and probably also AT1 receptor antagonists, at least in patients suffering from type 2 diabetes, slow disease progression to end-stage renal failure. This protective effect of drugs interfering with the renin-angiotensin system (RAS) are in part independent of reduction in systemic blood pressure, but involve normalization of glomerular hyperperfusion and hyperfiltration, restoration of altered glomerular barrier function, and reduction of stimulated tubular fluid reabsorption. Angiotensin II (ANG II) has emerged in the last decade as a multifunctional cytokine exhibiting many non-hemodynamic properties such as acting as a growth factor and profibrogenic cytokine, and even having proinflammatory properties. This review tries to bridge the classical hemodynamic actions of ANG II in the kidney with the more recently characterized effects of this vasopeptide. Finally, clinical implications are suggested based on data from clinical studies. A thorough understanding of the RAS is important to recognize the potential of nephroprotective strategies through inhibition of its components.
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PMID:The renin-angiotensin system and progression of renal disease: from hemodynamics to cell biology. 1241 25

Individuals with hypertension need to stay on therapy with antihypertensive medication to obtain the full benefits of blood pressure reduction. There are important differences in tolerability across antihypertensive drug classes, and these differences influence the extent to which patients are willing to continue taking their drugs. Three separate sources of evidence--postmarket surveillance studies, medical/prescription database studies, and discontinuation of study medication in long-term endpoint clinical trials--support the proposition that angiotensin II antagonists, the newest class of antihypertensives, are well tolerated, and that patients whose initial treatment is an angiotensin II antagonist are more likely to persist with therapy than patients who use other classes of antihypertensives. Recent landmark trials with losartan in hypertensive patients with left ventricular hypertrophy (Losartan Intervention For Endpoint reduction [LIFE]) and in diabetes (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL]) demonstrated excellent tolerability, a high level of persistence, and clinical benefits exceeding those provided by blood pressure control alone for the prototype angiotensin II antagonist in clinical settings.
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PMID:Compliance and persistence with newer antihypertensive agents. 1241 70

Cardiovascular complications due to micro- and microangiopathy are main causes of death of patients with type 2 diabetes. Principal role in development of these complications belong to hyperglycemia which triggers such pathological processes as endothelial dysfunction, oxidative stress, impairment of hemostasis and blood rheology. Therefore glucose lowering therapy is pathogenetic not only for diabetes but also for its cardiovascular complications. Glucose lowering drugs should be maximally effective and safe for the cardiovascular system. These requirements gliclaside which in addition to pronounced glucose lowering effect also acts on all links of the pathogenesis of micro- and macroangiopathies. While selecting cardiovascular drugs one should take into consideration their effect on carbohydrate metabolism and cardioprotective properties. Angiotensin converting enzyme inhibitors are leaders in this field.
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PMID:[Cardiovascular complications of type 2 diabetes]. 1249 72

In the past few years diabetes has become the leading cause of end-stage renal disease in all Western countries. A correlation between blood pressure and rate of progression in diabetic nephropathy was noted very early, and increased local activity of the renin angiotensin system was identified as a major pathophysiological mechanism for proteinuria and nephrosclerosis in diabetic patients. Angiotensin converting enzyme (ACE) inhibitors have been shown to slow progression of nephropathy in type 1 diabetic patients. The majority of diabetic patients with nephropathy, however, are suffering from type 2 diabetes and until last year there was no convincing evidence of ACE inhibitors being able to slow progression in type 2 diabetic patients with nephropathy. Three new studies now fill this gap, showing that angiotensin receptor blockers (ARB) are nephroprotective in patients with type 2 diabetes, independently of blood pressure. This review provides an in-depth discussion of the results of these studies and provides recommendations for patient management.
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PMID:Angiotensin receptor antagonists in patients with nephropathy due to type 2 diabetes. 1255 90

Angiotensin receptor blockers are a new class of agents that have made a major contribution to the treatment of hypertension. These agents effectively reduce blood pressure and are well tolerated. Other clinical trials have focused, however, on the much wider use of angiotensin receptor blockers in conditions such as congestive heart failure, postmyocardial infarction management, and diabetic nephropathy. Recent studies have provided evidence that these agents might confer target organ protection in hypertension that is equal to, and possibly better than, the benefits provided by conventional antihypertensive agents. Moreover, there is now little doubt that these drugs are effective alternatives to ACE inhibitors in heart failure and will become treatments of choice for patients with type 2 diabetes and nephropathy. Cardiovascular study outcomes have still not determined, however, whether high-risk patients would do better on angiotensin receptor blockers or angiotensin converting enzyme (ACE) inhibitors or a combination of both, except in cases of intolerance to ACE inhibitors.
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PMID:The angiotensin II receptor blockers: opportunities across the spectrum of cardiovascular disease. 1255 52

Losartan is an orally active, selective, nonpeptide, angiotensin II AT(1) receptor antagonist. Losartan 50 or 100 mg/day was significantly more effective than placebo in reducing the incidence of a doubling of serum creatinine, end-stage renal disease (ESRD) or death (43.5% vs 47.1%, p = 0.02) in a pivotal, well designed trial (Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan [RENAAL] study) in 1513 patients with type 2 diabetes mellitus and proteinuria. Losartan also significantly reduced the incidence of doubling of serum creatinine level (p = 0.006), ESRD (p = 0.002), ESRD or death (p = 0.01) and doubling of serum creatinine and ESRD (p = 0.01) compared with placebo in the RENAAL trial. There were similar incidences of overall mortality and morbidity and mortality from cardiovascular causes between treatment groups. In addition, data from several nonblind and double-blind studies indicates that losartan effectively reduces the mean albumin excretion rate. Two double-blind studies show that losartan has similar effects to enalapril on kidney function. Data from 4058 patients (3300 with essential hypertension) who have received losartan (10-150 mg/day) in clinical trials indicate it is well tolerated. In the RENAAL study 17.2% and 21.7% of losartan and placebo recipients discontinued treatment because of adverse events, but causality was not determined.
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PMID:Losartan in diabetic nephropathy. 1255 62

Insulin resistance is involved in the pathogenesis of type 2 diabetes, hypertension, and atherosclerosis. Angiotensin (Ang) converting enzyme inhibitors and Ang II type 1 receptor antagonists improve insulin resistance in patients with essential hypertension, which suggest that tissue Ang II is involved in insulin resistance in patients with hypertension. To investigate the participation of tissue Ang II in insulin resistance associated with hypertension, we evaluated the Ang II-generating system in leukocytes and its relation to insulin resistance in patients with essential hypertension. Eighteen patients with essential hypertension participated in this study. Ang II was separated from leukocytes by reversed-phase high-performance liquid chromatography and measured by radioimmunoassay. Insulin resistance was evaluated by determining the steady-state of plasma glucose (SSPG) concentration. The Ang I- and Ang II-generating activities were evaluated in human leukocytes. Human leukocytes have Ang I- and Ang II-generating activities. The Ang II-generating activity was significantly inhibited by pepstatin A. Leukocyte Ang II level does not correlate with BP or plasma Ang II level in patients with essential hypertension. Leukocyte Ang II level strongly correlates with SSPG concentration, and significantly correlates with body mass index and plasma insulin, and with leptin levels in patients with essential hypertension. Leukocyte Ang II may be directly associated with insulin resistance.
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PMID:Leukocyte angiotensin II levels inpatients with essential hypertension:relation to insulin resistance. 1255 79

Interest in the renin-angiotensin-aldosterone system (RAAS) has increased since the development of angiotensin-converting enzyme (ACE) inhibitors. It has been discovered that the potential uses of this class of treatment extend far beyond their initial developmental role as antihypertensives, and they are now used routinely in the treatment of heart failure, nephropathy, myocardial infarction and diabetes. However, there is more to RAAS blockade than just inhibition of angiotensin II, and inhibition of aldosterone is becoming recognised as an additional therapeutic manoeuvre in chronic heart failure. Since inhibition of the RAAS at the level of ACE is now seen to be an important therapy in diabetes; the purpose of this article is to explore the potential benefits of additional aldosterone inhibition in Type 2 diabetes mellitus.
J Renin Angiotensin Aldosterone Syst 2002 Sep
PMID:The potential benefits of aldosterone antagonism in Type 2 diabetes mellitus. 1256 64

Angiotensin II (Ang II), acting on the AT1 and AT2 receptors in mammalian cells, is the vasoactive component of the renin-angiotensin system (RAS). Several components of the RAS have been demonstrated in different tissues, including adipose tissue. Although the effects of Ang II on metabolism have not been studied widely, it is intriguing to assume that components of the RAS produced by adipocytes may play an autocrine, a paracrine and/or an endocrine role in the pathophysiology of obesity and provide a potential pathway through which obesity leads to hypertension and type 2 diabetes mellitus. In the first part of this review, we will describe the production of Ang II, the different receptors through which Ang II exerts its effects and summarize the concomitant intracellular signalling cascades. Thereafter, potential Ang II-induced mechanisms, which may be associated with obesity and obesity-related disorders, will be considered. Finally, we will focus on the different pharmaceutical agents that interfere with the RAS and highlight the possible implications of these drugs in the treatment of obesity-related disorders.
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PMID:Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders. 1260 26

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6


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