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

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.
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PMID:Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. 1243 44

The most important factor that prevents the progression of renal damage in diabetes mellitus, beside the improvement of blood glucose control, is tight BP control. The tenet of tight BP control may be defined as the lowest BP level one can accomplish using antihypertensive therapy that is at the same time compatible with the absence of untoward side effects. In fact, both the Framingham Heart Study in nondiabetic normal subjects and the United Kingdom Prospective Diabetes Study in type 2 diabetic patients showed that systolic values as low as 108 to 111 mmHg and diastolic values as low as 70 to 71 mmHg are significantly associated with decreased cardiovascular mortality and morbidity. However, 45 to 50% of the patients with type 2 diabetes mellitus and hypertension have systolic BP levels above 140 mmHg during antihypertensive therapy, particularly when using monotherapy. Thus the issue regarding the choice of which drugs one should use to treat hypertension became critical from a clinical point of view. Pharmaceutical compounds, which inhibit the renin-angiotensin system, have become the first-choice treatment in patients with diabetes mellitus and incipient and advanced renal complications. The present brief review analyzes the effects of calcium channel blockers (CCB) on cardiovascular and renal complications in diabetes mellitus. The review discussed those studies that directly and blindly compared CCB with angiotensin-converting enzyme (ACE) inhibitors and with angiotensin II AT(1) receptor blockers (ARB). Furthermore, size of the population recruited in each trial was used as a criterion of priority in the selection of the reports from the available literature. From the point of view of cardiovascular complications, the results of these studies showed a slightly better benefit of CCB on stroke, whereas ACE inhibitors better prevented the occurrence of myocardial infarction and congestive heart failure. On the other hand, recent observations demonstrated that also ACE inhibitors and ARB are effective in the primary and secondary prevention of stroke, although these studies did not directly compare these compounds with CCB. With regard to the outcome of renal complications, both ARB and ACE inhibitors more effectively prevented the progression of renal damage among the patients with overt nephropathy than CCB. On the contrary, both CCB and ACE inhibitors were equally effective on blunting the decay of GFR in diabetic patients who do not have overt proteinuria. However, ACE inhibitors and ARB more markedly decreased the rate of albumin excretion rate in the range of both microalbuminuria and macroalbuminuria. Recent advances in the understanding of the pathogenesis of abnormalities of albumin excretion rate and of atherosclerosis are also discussed. Both mechanical stress, mainly secondary to systolic hypertension, and elevated circulating and tissue levels of angiotensin II, partially independent from each other, cause excessive generation of superoxide compounds. This chain reaction of events in turn leads to disorders of structural components of glomerular filter and to damage of the vascular wall. Systolic BP control (<130 mmHg) is not adequately accomplished in the majority of the patients treated only with ACE inhibitors and ARB, even in association with diuretics. Poor BP control may lead to excessive systemic mechanical stress at the vascular level despite satisfactory inhibition of angiotensin II effects. In conclusion, one can suggest that CCB are useful and often indispensable pharmaceutical compounds, beside ACE inhibitors and ARB, to accomplish tight BP control (<130/85 mmHg), a target that is unlikely to be successfully maintained in the overall population of type 2 diabetic patients only by ACE inhibitors or ARB, as monotherapy. However, ACE inhibitors and ARB might be considered first-choice drugs in the treatment of hypertension in diabetes mellitus, mainly because of a better renoprotection.
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PMID:Cardiovascular and renal protection in type 2 diabetes mellitus: the role of calcium channel blockers. 1246 17

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the development of clinical proteinuria or delay the progression of nephropathy in type 2 diabetes. The IRMA study showed that irbesartan is more effective than conventional therapy in preventing the development of clinical proteinuria and in favoring the regression to normoalbuminuria for comparable BP control in patients with incipient nephropathy. The IDNT and RENAAL trials showed that ARB are more effective than traditional antihypertensive therapies in reducing progression toward end-stage renal failure (ESRF) in type 2 diabetic patients with overt nephropathy independently of changes in BP. Moreover, a reduction in hospitalizations for heart failure was demonstrated for ARB-treated patients compared with placebo. Furthermore, the LIFE study showed that losartan is more effective than conventional therapy in reducing cardiovascular morbidity and mortality in a cohort of diabetic patients with hypertension and left ventricular hypertrophy. In conclusion, ARB seem to be effective in both preventing renal damage and reducing progression toward ESRF in type 2 diabetic patients. Thus, the guidelines for the prevention and treatment of diabetic nephropathy are now changed. In type 1 diabetes ACE-I are the first-choice drug; in type 2 diabetes, ARB are considered first-choice drugs in secondary prevention as well as ACE-I and have been now elected the unique first-choice drug in tertiary prevention of ESRF. Finally, ARB should be considered as the first-choice drug in cardiovascular prevention too, as well as ACE-I.
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PMID:Renal and cardiovascular protection in type 2 diabetes mellitus: angiotensin II receptor blockers. 1246 18

Diabetic nephropathy is the most frequent cause of end-stage renal failure. One of the crucial factors in a development of renal and cardiovascular complications of diabetes is genetic predisposition. The genes of the renin-angiotensin system are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was the evaluation of a possible role of genetic polymorphisms of some of the RAS system genes in the nephropathy in type 2 diabetes. The study was performed in 117 patients with diabetic nephropathy, compared with 200 healthy subjects as a control group. The following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme gene (ACE), M235T of the angiotensinogen gene (AGT) and A1166C of the angiotensin II type 1 receptor gene (AT1R) were evaluated by polymerase chain reaction (PCR). No statistically significant differences between groups were found in the allele frequency and genotype distribution for ACE and AGT polymorphisms. The results for the AT1R gene polymorphism revealed significant differences in allele and genotype frequencies. The homozygous CC genotype was more frequent in patients with diabetic nephropathy than in control group. Both genotypes with the C allele (AC + CC) were found in 56% of patients compared to 38% in control group. These results suggest increased susceptibility to diabetic nephropathy in individuals carrying the CC genotype. Therefore, the A1166C polymorphism of the AT1R gene could be a potential genetic marker for increased susceptibility to renal complications in type 2 diabetes.
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PMID:[Association of the renin-angiotensin system gene polymorphism with nephropathy in type II diabetes]. 1247 91

Diabetic nephropathy is the number one cause of endstage renal disease in the United States. Blockade of the renin angiotensin system (RAS) is important in the treatment of diabetic nephropathy. With the reports of recently completed trials examining the role of angiotensin receptor blockers (ARBs) in type 2 diabetic nephropathy, the question has arisen as to which agents are best to block the RAS in type 2 diabetes. ACE inhibitors have been to preserve renal function in type 1 diabetics with nephropathy in large, randomized, placebo controlled trials, but such data is lacking in type 2 diabetes. Neverthelesss, ACE inhibitors have been recommended for use in type 2 diabetic nephropathy for some time. In type 2 diabetics, ACE inhibitors may have a role in preventing development of nephropathy, and, importantly, ACE inhibitors have been shown to reduce cardiovascular disease in diabetics with and without nephropathy. In addition, ACE inhibitors have beneficial effects on other diabetic complications such as retinopathy and neuropathy. Until better comparative data between ACE inhibitors and ARBs on nephropathy and cardiovascular outcomes is available, ACE inhibitors should remain an important consideration for treatment of diabetic nephropathy.
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PMID:Therapeutic controversies in hypertension management: angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers for diabetic nephropathy? A case for ACE inhibitors. 1247 55

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

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.
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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

The renin-angiotensin system plays a key role in the progression of kidney disease, in addition to its well-described role in the maintenance of extracellular fluid volume and blood pressure. Recent studies have shown that blockade of the renin-angiotensin system at the level of the angiotensin II type 1 receptor can have important effects on proteinuria and the rate of progression of kidney disease in patients with type 2 diabetes mellitus. This review first discusses recent experimental studies relating angiotensin II to kidney function in diabetes mellitus and changes in glomerular permselectivity, and then focuses on recent clinical trials with angiotensin II receptor blockers in patients with type 2 diabetes mellitus.
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PMID:Angiotensin II and the glomerulus: focus on diabetic kidney disease. 1264 18

Diabetic nephropathy is a major cause of morbidity and mortality in patients with diabetes; it occurs in about one third of such patients. The course of nephropathy is better defined and similar for both type 1 and type 2 diabetes. Patients initially develop microalbuminuria (albumin excretion rates [AERs] between 20 and 200 micrograms/min), then overt nephropathy (AER > or = 200 micrograms/min), and finally a decline in glomerular filtration rate (GFR) eventuating in end-stage renal disease. Although metabolic control has long been hypothesized as a contributor to the development of nephropathy, it is only in recent years that this hypothesis has been proven. A number of observational studies have shown correlations between glycemic control and the development of various levels of albuminuria and also declines in GFR. However, large long-term prospective, randomized, interventional studies have now definitely proven that improved metabolic control that achieves near-normoglycemia can significantly decrease the development and progression of diabetic nephropathy as well as other long-term complications of diabetes, including retinopathy and neuropathy. It is now conceivable that the achievement of near-normoglycemia, plus medications that inhibit the renin-angiotensin system if microalbuminuria develops, may greatly decrease the numbers of patients eventually requiring renal replacement therapy.
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PMID:The relationship between glucose control and the development and progression of diabetic nephropathy. 1264 59


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