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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although angiotensin II receptor blockers (ARBs) have been recommended as a first line of anti-hypertensive agents in patients with diabetes, it remains unclear whether ARBs have a favorable effect on insulin action and triglyceride (TG) metabolism, both of which are impaired in type 2 diabetes. In this study we addressed this issue by investigating how a newly developed ARB, olmesartan medoxomil, influenced insulin sensitivity and TG metabolism in fructose-fed rats, a representative animal model of insulin resistance. Olmesartan was administrated as a 0.01% drinking solution ad libitum to rats either fed normal chow or fructose-enriched chow (60%) for 21 days. Olmesartan treatment markedly decreased both systolic and diastolic blood pressure in both chow-fed and fructose-fed animals. The area under the curve of insulin (AUCI) was substantially greater in fructose-fed rats in the intravenous glucose tolerance test, and olmesartan treatment significantly reduced the AUCI. Olmesartan significantly improved the insulin sensitivity index in fructose-fed rats assessed by Bergman's minimal model without affecting insulin-independent glucose disposal. Olmesartan significantly decreased plasma TG and non-esterified fatty acid levels in fructose-fed rats without affecting lipoprotein lipase mass. The TG secretion rate determined by the triton WR1339 technique was two-fold higher in fructose-fed rats, but olmesartan restored the TG secretion to a normal rate. Olmesartan did not affect plasma parameters, insulin sensitivity or TG metabolism in chow-fed rats. Olmesartan ameliorates insulin resistance and overproduction of TG in fructose-fed rats, and these effects appear to be independent of its hypotensive action.
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PMID:Olmesartan medoxomil, an angiotensin II receptor blocker ameliorates insulin resistance and decreases triglyceride production in fructose-fed rats. 1512 87

Diabetes mellitus and impaired glucose tolerance (IGT) are common disorders, and their prevalence is predicted to increase over the next several decades. The major serious complication of these disorders is large vessel atherosclerosis leading to myocardial infarction and stroke. Aggressive control of hypertension and dyslipidemia can significantly reduce risk for cardiovascular events, but a large amount of residual cardiovascular disease remains. A major remaining question is the potential role of aggressive glucose control for reducing macrovascular event rates in patients with diabetes. An ongoing trial addresses this issue, and a large number of other concurrent trials address several novel therapeutic strategies to reduce further the cardiovascular complications of diabetes or IGT. Many of these strategies test approaches that may directly target the vessel wall. Therapeutic modalities currently being evaluated include thiazolidinediones, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. Most of these trials will report their findings in the next 5 years. It is likely that the results of ongoing trials will significantly improve our approach to managing cardiovascular risk in patients with diabetes and IGT.
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PMID:Strategies in ongoing clinical trials to reduce cardiovascular disease in patients with diabetes mellitus and insulin resistance. 1517 14

Recent evidence suggests that blockade of the renin-angiotensin system ameliorates diabetes-induced cardiac dysfunction, but the mechanisms involved in this process remain elusive. We investigated the effect of treatment with an angiotensin II receptor blocker, losartan, on the metabolic and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 20 mg x kg(-1) x day(-1) losartan for 8 weeks. Insulin and beta-adrenergic stimulation failed to increase the glucose uptake rate in STZ cardiomyocytes, whereas the alpha-adrenergic effect persisted. Concurrently, a typical prolongation of action potential duration (APD) and a decrease of transient outward current (I(to)) were recorded in patch-clamped STZ myocytes. Treatment with losartan did not affect body weight or glycemia of diabetic or control animals. However, in losartan-treated STZ-induced diabetic rats, beta-adrenergic-mediated enhancement of glucose uptake was completely recovered. APD and I(to) were similar to those measured in losartan-treated control rats. A significant (P < 0.0001) correlation between metabolic and electrophysiological parameters was found in control, diabetic, and losartan-treated diabetic rats. Thus, angiotensin receptor blockade protects the heart from the development of cellular alterations typically associated with diabetes. These data suggest that angiotensin receptor blockers may represent a new therapeutic strategy for diabetic cardiomyopathy.
Diabetes 2004 Jul
PMID:Restoration of cardiomyocyte functional properties by angiotensin II receptor blockade in diabetic rats. 1522 Feb 22

Potentially important new findings have recently been reported concerning the so-called metabolic syndrome in relation to the renin-angiotensin system, ie, that treatment with inhibitors of the angiotensin-converting enzyme (ACE) not only decreases blood pressure levels but prevents the development of diabetes mellitus. The new findings described in this article highlight the potential role of the ACE system in the regulation of insulin sensitivity, thus contributing to the development of type 2 diabetes and metabolic syndrome. In addition to the well known selective effects of ACE inhibitors and angiotensin II receptor blockers in reducing microalbuminuria in diabetic patients, the potential ability of these drugs to reduce the risk of diabetes and the metabolic syndrome would support their use as first line agents not only in diabetic patients but also in selected groups of hypertensive patients, who are particularly at risk of developing metabolic complications. This information supports the Joint Guidelines for the Management of Arterial Hypertension by the European Society of Hypertension and the European Society of Cardiology, which highlight the crucial role of ACE inhibitors and the angiotensin II receptor blockers in preventing the development of diabetes in hypertensive patients.
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PMID:The role of the renin angiotensin hormonal system in the metabolic syndrome and type 2 diabetes. 1524 41

Older patients with hypertension are often inadequately treated due to misconceptions regarding reasonable goal blood pressures or concerns about treatment side effects. Adequately treating hypertension can yield impressive benefits in terms of improved morbidity and enhanced quality of life in persons of any age. Antagonists of the renin-angiotensin-aldosterone system are especially effective in older persons, many of whom have concomitant conditions such as diabetes mellitus, renal dysfunction, and other cardiovascular risk factors. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been shown to improve many of the complications of hypertension, including left ventricular hypertrophy and renal disease. Results of recent key studies such as Losartan Intervention For Endpoint Reduction in Hypertension (LIFE), Valsartan in Heart Failure Trial (Val-HeFT), Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM), and Valsartan in Acute Myocardial Infarction (VALIANT) add to the evidence that angiotensin II receptor blockers are well suited for the treatment of hypertension in older patients. These trials also indicate that they are appropriate therapy for heart failure patients and for patients who have experienced acute myocardial infarction, particularly those who are unable to tolerate an angiotensin-converting enzyme inhibitor.
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PMID:Angiotensin II receptor blockers in older patients. 1526 63

NF-kappaB-dependent pathways play an important role in macrophage infiltration and kidney injury. NF-kappaB is regulated by angiotensin II (AII). However, the role of this pathway in diabetic nephropathy has not been clearly delineated. First, the activation of NF-kappaB, monocyte chemoattractant protein-1 (MCP-1), and macrophage infiltration in the diabetic kidney were explored, in a temporal manner. The active subunit of NF-kappaB, p65, was elevated in the diabetic animals in association with increased MCP-1 gene expression and macrophage infiltration. Second, the effects of treatment for 4 wk with the AII type 1 receptor antagonist valsartan, the AII type 2 receptor antagonist PD123319, or pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB and on these parameters were assessed. These treatments were associated with a reduction in p65 activation, MCP-1 gene expression, and macrophage infiltration. These findings demonstrate a role for activation of NF-kappaB, in particular the p65 subunit, in the pathogenesis of early renal macrophage infiltration in experimental diabetes. In the context of the known proinflammatory effects of AII, it is postulated that the renoprotection conferred by angiotensin II receptor antagonism is at least partly related to the inhibition of NF-kappaB-dependent pathways.
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PMID:Interactions between angiotensin II and NF-kappaB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy. 1528 99

The angiotensin II receptor blockers (ARBs), are highly selective for the AT1 subtype and will block the effects of angiotensin II on peripheral vessels. Several short- and long-term studies have shown these agents to be safe and effective antihypertensive drugs. Since monotherapy of hypertension may be ineffective in lowering the blood pressure to goal, the use of an ARB, especially in combination with a diuretic or another medication, is frequently necessary to bring the blood pressure <140/90 mm Hg (<130/80 mm Hg among people with diabetes mellitus or chronic renal failure), according to JNC 7 guidelines. Besides hypertension, the ARBs have been shown to reduce left ventricular hypertrophy in hypertensive patients. Other benefits of these medications, as well as the angiotensin I converting enzyme inhibitors (ACEIs), include a decrease in cardiovascular morbidity and mortality in patients with heart failure, or hypertensive diabetic nephropathy with proteinuria. Some of the beneficial effects noted with the ACEIs and ARBs (congestive heart failure, left ventricular hypertrophy), have also been demonstrated with the use of b blockers alone and in combination with a diuretic. These drugs, i.e., b blockers, ARBs, and ACEIs, seem to exert their beneficial action through the blockade of the renin-angiotensin-aldosterone system. The role of this system in cardiovascular remodeling and its blockade will be discussed in this review, which will specifically summarize data with the ARB, valsartan.
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PMID:Clinical experience with angiotensin receptor blockers with particular reference to valsartan. 1530 83

Overweight/obesity represent an underestimated risk factor of renal disease. The incidence of obesity-related glomerulopathy (ORG) tremendously increased within the last decade. The first sign of renal damage in overweight conditions is microalbuminuria or proteinuria, indicating the potential risk of its progression to renal insufficiency and the development of premature cardiovascular events. In the early stage of obesity renal hemodynamics are characterized by a renal hypercirculation and glomerular hyperfiltration, particularly in the presence of hypertension. The hyperfiltration is especially harmful in patients with pre-existing inflammatory and metabolic renal disease, or under the conditions of reduced renal mass. Histopathologically, ORG is characterized by glomerulomegaly with/without signs of focal segmental glomerulosclerosis. Pathogenetically, numerous factors are involved, e.g. enhanced glomerular capillary pressure, adrenergic nerve overactivity, inappropriate activation of the renin-angiotensin-aldosterone system, insulin resistance, hyperinsulinemia and hyperleptinemia, dyslipidemia, enhanced clotting tendency and sodium retention. Diabetic nephropathy is one of the most serious complications of obesity-induced diabetes. In the industrial nations type 2 diabetes is the single most frequent cause of end-stage renal disease. After kidney transplantation, overweight/obesity is associated with a less favourable prognosis for the survival of the graft and the patient. Incidence of renal cell carcinomas is enhanced in overweight/obesity. Obesity-related renal disease may be prevented/postponed by an early weight reduction, by dietary intervention combined with physical exercise. In the advanced stages of renal disease benefits of weight reduction are minimal. Concomitant administration of angiotensin-converting-enzyme inhibitors or angiotensin II receptor 1 blockers exerts antiproteinuric effects and thereby aid in retarding the disease progression. Aimed prevention and treatment of obesity represent a challenge for the healthcare system. The concerted action of physicians, patients and the public health authorities is needed.
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PMID:[Overweight and obesity--risk factors in the development and progression of renal disease]. 1532 63

The effect of the angiotensin II receptor blocker, candesartan cilexetil, on proteinuria was examined in a prospective, multicenter, randomized, double-blind study in Japanese subjects with type 2 diabetes. This study enrolled diabetic subjects with confirmed proteinuria into four groups for 12 weeks of treatment with placebo or candesartan cilexetil 2, 4, or 8 mg. The contribution of the angiotensin converting enzyme (ACE) gene polymorphism to the effect of candesartan cilexetil was also examined. In 127 subjects, candesartan cilexetil showed a dose-related reduction in proteinuria after 12 weeks of treatment (F = 9.45, P = 0.0013), with a 18.1% reduction in the 4-mg group, and a 5.8% reduction in the 8-mg group, in contrast to a 32.2% increase in the placebo group, and a 0.8% increase in the 2-mg group. These results indicate that candesartan cilexetil is useful in reducing proteinuria in diabetic subjects when compared with placebo. In addition, candesartan cilexetil seems to be effective in subjects with both the II and DD genotypes of the ACE gene.
Diabetes Res Clin Pract 2004 Oct
PMID:Antiproteinuric effect of candesartan cilexetil in Japanese subjects with type 2 diabetes and nephropathy. 1536 66

Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends starting treatment with a thiazide diuretic or, when BP is >20/10 mm Hg above goal or in patients with diabetes, using two different antihypertensive agents. Searches of Medline, EMBASE, and BIOSIS databases identified four similarly designed, randomized, factorial studies comparing various doses of angiotensin II receptor blockers with hydrochlorothiazide as monotherapy and in combination. The methodology and results of these studies were compared. The primary efficacy end point in these studies was a decrease from baseline in mean diastolic BP after 8 weeks of therapy. All currently available angiotensin I receptor blocker/hydrochlorothiazide combinations evaluated (irbesartan, olmesartan medoxomil, telmisartan, and valsartan plus hydrochlorothiazide) produced significant systolic BP and diastolic BP reductions. Olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg provided the largest mean reduction in absolute and placebo-corrected systolic BP/diastolic BP. For all angiotensin II receptor blocker/hydrochlorothiazide combinations evaluated, > or =63% of patients achieved a diastolic BP response (diastolic BP <90 mm Hg or > or =10-mm Hg reduction). In conclusion, the combination of an angiotensin II receptor blocker and hydrochlorothiazide produces more substantial BP responses than monotherapy with either component.
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PMID:Antihypertensive efficacy of angiotensin receptor blockers in combination with hydrochlorothiazide: a review of the factorial-design studies. 1547 Feb 86


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