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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

Increased (intra)renal activity of the renin-angiotensin system may cause a persistent increase in renovascular resistance and intraglomerular pressure in patients with diabetes, thus contributing to the development of diabetic renal damage. The effect of chronic angiotensin II subtype 1 receptor blockade on (intra)renal hemodynamics in patients with type 2 diabetes was examined in a double-blind parallel group study. Patients were treated with 40 mg of olmesartan (n = 19) or placebo (n = 16), and renal hemodynamics were assessed before and after 12 wk of treatment using inulin and para-aminohippurate clearance techniques. Olmesartan significantly reduced 24-h ambulatory systolic and diastolic BP (both P < 0.05). In parallel, effective renal plasma flow increased significantly from 602 +/- 76 to 628 +/- 87 ml/min per 1.73 m(2), whereas filtration fraction and renovascular resistance decreased significantly (all P < 0.05). With placebo treatment, effective renal plasma flow decreased and filtration fraction increased significantly (both P < 0.05). GFR was not affected by both treatments. Active plasma renin concentration increased considerably (P < 0.05) with olmesartan therapy but remained unchanged with placebo treatment. Nitric oxide metabolism (plasma nitrate and nitrite) and asymmetric dimethylarginine blood levels were not affected by olmesartan and placebo therapy. In contrast, plasma 8-isoprostane 15(S)-8-iso-prostaglandin F(2a) concentration, a biochemical marker of oxidative stress, decreased significantly (P < 0.05) with olmesartan treatment. Chronic angiotensin II subtype 1 receptor blockade decreases (intra)renal vascular resistance and increases renal perfusion despite significant BP reduction. In addition, it significantly reduces oxidative stress. These effects of angiotensin II receptor antagonists may contribute to their beneficial long-term renal effects in patients with type 2 diabetes.
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PMID:Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance in patients with type 2 diabetes. 1571 29

The incidence of type-2 diabetes is increasing throughout the world. By 2010, 350 million people will have this disease. Microalbuminuria is present in more than one third, for some at diabetes diagnosis. Rather than a complication, it is an indication of a vascular disorder that is part of the metabolic syndrome. 25% will develop end-stage kidney failure. Several studies have identified microalbuminuria or proteinuria as an independent cardiovascular risk factor. Others have shown that antihypertensive treatments acting on the renin-angiotensin system (ACE inhibitors, ARBs agents) can reduce the progression of nephropathy in people with hypertension, type 2 diabetes and microalbuminuria. The "nephroprotective" effects of these drug classes, beyond their role in blood-pressure reduction, are suggested by modifications in renal structure and protein expression. But no study has so far examined their value in primary prevention in persons with type 2 diabetes without--but at risk of developing--microalbuminuria. The Roadmap study (Randomized Olmesartan And Diabetes Microalbuminuria Prevention Study) of primary prevention has as its objective measurement of the impact of ARBs (olmesartan 40 mg/d) treatment on renal outcome in 4400 patients with type 2 diabetes without microalbuminuria. Follow-up of this placebo-controlled study will last for 5 years. Conducted in 200 European centers, its results are expected for 2012.
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PMID:[Primary cardiorenal prevention in patients with type-2 diabetes. The Roadmap study]. 1626 93

Diabetic nephropathy has developed into a worldwide epidemic and is responsible for the majority of end-stage renal disease in most countries. Antihypertensive treatment slows the progression of the disease. In addition, blockade of the renin-angiotensin system reduces the degree of albuminuria and angiotensin II receptor blockers (ARBs) have been shown to delay the progression from microalbuminuria to overt proteinuria in patients with diabetes. However, few studies have examined whether the initial stage of diabetic nephropathy (i.e. the development of microalbuminuria) in patients with type 2 diabetes can be slowed or prevented by ARB treatment. The Randomised Olmesartan And Diabetes MicroAlbuminuria Prevention (ROADMAP) study is a placebo-controlled, multicentre, double-blind, parallel group study investigating the effect of the ARB, olmesartan medoxomil, on the incidence of microalbuminuria. A total of 4400 type 2 diabetes patients with normoalbuminuria will be randomized to treatment with 40 mg of olmesartan medoxomil once daily or placebo. Goal blood pressure will be 130/80 mmHg. The primary endpoint of the study is the occurrence of microalbuminuria. In ROADMAP, we will also assess as secondary endpoints the effects of olmesartan on fatal and non-fatal cardiovascular events in patients with diabetes. In addition, within subgroups of the ROADMAP patients, the effects of olmesartan on retinopathy and other microvascular circulations will be analysed. The study is expected to last a median of 5 years. The ROADMAP study will answer the question whether an ARB can prevent or delay the onset of microalbuminuria and whether this translates into protection against cardiovascular events and renal disease.
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PMID:Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. 1650 90

Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 +/- 2.7 versus 2.9 +/- 2.2 muU/ml x mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-alpha, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 +/- 16 versus 92 +/- 14 mg/dl; P < 0.05), insulin (23.1 +/- 8.8 versus 19.9 +/- 9; P < 0.05), HOMA index (6.0 +/- 2.7 versus 4.7 +/- 2.8; P < 0.05), and glycated hemoglobin (5.33 +/- 0.58 versus 4.85 +/- 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 +/- 100 versus 370 +/- 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy.
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PMID:Insulin resistance, inflammatory biomarkers, and adipokines in patients with chronic kidney disease: effects of angiotensin II blockade. 1713 Feb 63

Fasudil, a Rho-kinase inhibitor, may improve insulin signaling. However, its long-term effect on metabolic abnormalities and its preventive effect on diabetic nephropathy are still unknown. We assessed these effects of fasudil in insulin-resistant diabetic rats, comparing them with those of an angiotensin II receptor blocker, olmesartan. Male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka, non-diabetic control, rats at 15 weeks of age were used. OLETF rats were randomized to receive a low or a high dose of fasudil or olmesartan for 25 weeks. To examine the therapeutic effects after the development of diabetes, OLETF rats at 30 weeks of age were given fasudil for 10 weeks. Administration of high-dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. High-dose olmesartan also decreased hemoglobin A1c and increased serum adiponectin. There was a significant correlation between hemoglobin A1c and serum adiponectin or free fatty acid levels. The treatment with high-dose fasudil ameliorated proteinuria, glomerulosclerosis, renal interstitial fibrosis, and macrophage infiltration in OLETF rats. Olmesartan, even at the low dose, suppressed renal complications. The treatment with fasudil after the development of diabetes improved the metabolic abnormalities in OLETF rats, but could not suppress the progression of nephropathy. We conclude that the long-term treatment with fasudil prevents the development of diabetes, at least in part, by improving adipocyte differentiation in insulin-resistant diabetic rats. Early use of fasudil may prevent diabetic nephropathy.
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PMID:A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats. 1733 27

Angiotensin II type-1 receptor blockers (ARBs) are regarded as first-line treatments for type-2 diabetes with hypertension. Despite the availability of various types of ARBs, there are no comparative studies of their effects on patients with diabetes. In this open-label prospective crossover study, we compared the effects of olmesartan (20 mg/day) and telmisartan (40 mg/day). Twenty Japanese early-stage type-2 diabetes patients with hypertension treated with valsartan (80 mg/day) for at least 8 weeks were recruited to this study. At study entry, valsartan was changed to olmesartan (20 mg/day) or telmisartan (40 mg/day) and administered for 8 weeks. The drugs were then switched and treatment was continued for another 8 weeks. We analyzed the blood pressure lowering effects of each drug by 24-h ambulatory blood pressure monitoring at 0, 8, and 16 weeks. Simultaneously, we measured metabolic parameters and inflammation markers. Olmesartan lowered mean systolic and diastolic blood pressure more significantly than did telmisartan. While there were no differences between the groups in metabolic parameters, including HbA1c and adiponectin, the decreases in serum interleukin-6 and highly sensitive C-reactive protein were more significant by olmesartan treatment. Our results indicate that olmesartan has more potent arterial blood pressure lowering and anti-inflammatory effects than telmisartan.
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PMID:Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension. 1836 12

In addition to the juxtaglomerular apparatus, renin is also synthesized in renal tubular epithelium, including the collecting duct (CD). Angiotensin (Ang) II differentially regulates the synthesis of juxtaglomerular (inhibition) and CD (stimulation) renin. Because diabetes mellitus, a disease with high intrarenal renin-Ang system and Ang II activity, is characterized by high prorenin levels, we hypothesized that the CD is the major source of prorenin in diabetes. Renin granular content was visualized using in vivo multiphoton microscopy of the kidney in diabetic Munich-Wistar rats. Diabetes caused a 3.5-fold increase in CD renin, in contrast to less pronounced juxtaglomerular changes. Ang II type 1 receptor blockade with Olmesartan reduced CD renin to control levels but significantly increased juxtaglomerular renin. Using a fluorogenic renin assay, the prorenin component of CD renin content was measured by assessing the difference in enzymatic activity of medullary homogenates before and after trypsin activation of prorenin. Trypsinization caused no change in control renin activity but a 5-fold increase in diabetes. Studies on a CD cell line (M1) showed a 22-fold increase in renin activity after trypsinization and a further 35-fold increase with Ang II treatment. Therefore, prorenin significantly contributes to baseline CD renin. Diabetes, possibly via Ang II, greatly stimulates CD prorenin and causes hyperplasia of renin-producing connecting segments. These novel findings suggest that, in a rat model of diabetes, prorenin content and release from the CD may be more important than the juxtaglomerular apparatus in contrast to the existing paradigm.
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PMID:The collecting duct is the major source of prorenin in diabetes. 1841 93

Dietary obesity is associated with type 2 diabetes and cardiovascular diseases, although the underlying mechanism is unknown. This study was undertaken to elucidate the role of angiotensin II and apoptosis signal regulating kinase-1 (ASK1) in obesity/diabetes-associated cardiovascular complications and hepatic steatosis. Mice fed a high-fat diet were treated with olmesartan, an angiotensin II type 1 receptor blocker, to elucidate the role of angiotensin II in diabetic mice. Treatment of mice fed a high-fat diet with olmesartan markedly suppressed cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling, induced by obesity/diabetes. Moreover, olmesartan suppressed the disruption of the vascular endothelial NO synthase dimer in diabetic mice. Olmesartan also significantly prevented hepatic steatosis and fibrosis in diabetic mice. These beneficial effects of olmesartan on diabetic mice were associated with the attenuation of ASK1 activation in these mice. ASK1-deficient mice and wild-type mice were compared, regarding the effects of a high-fat diet. A comparison between ASK1-deficient and wild-type mice showed that ASK1 deficiency attenuated cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling induced by obesity/diabetes. The amelioration of vascular endothelial impairment by ASK1 deficiency was attributed to the prevention of endothelial NO synthase dimer disruption. ASK1 deficiency also significantly lessened hepatic steatosis in diabetic mice. In conclusion, our work provided the evidence that ASK1 is significantly activated in diet-induced diabetic mice and contributes to cardiovascular diseases and hepatic steatosis in diabetic mice. Moreover, the beneficial effects of angiotensin II inhibition on dietary diabetic mice seem to be mediated by the inhibition of ASK1 activation.
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PMID:Olmesartan prevents cardiovascular injury and hepatic steatosis in obesity and diabetes, accompanied by apoptosis signal regulating kinase-1 inhibition. 1867 90

Elevated systolic blood pressure increases the risk of cardiovascular events, as shown by a number of meta-analyses of large-scale clinical trials. As concerns the prognostic impact of the metabolic syndrome on cardiovascular events, few large-scale studies are available in the Japanese hypertensive population. The prospective, large-scale, observational OMEGA (Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement) study sought to examine the relationship between the incidence of cardiovascular disease (CVD) and achieved blood pressure, metabolic syndrome, lifestyle factors and other risk factors for CVD in patients with hypertension. Of the 15,313 enrolled patients from 2,219 institutions in Japan, we report here the baseline characteristics of the 14,841 eligible patients whose baseline data were collected as of October 31, 2007. Men and women 50 to 79 years old (mean age 65) with physician-diagnosed hypertension were enrolled, and all patients were treated with open-label olmesartan medoxomil (5 to 40 mg daily). The majority of patients (75%) had mild to moderate hypertension. The prevalences of dyslipidemia and diabetes mellitus were 48% and 24%, respectively. The metabolic syndrome was identified in 48% and 19% of the evaluable men and women, respectively, using the criteria of the Japanese Society of Internal Medicine. Men with the metabolic syndrome were at the greatest risk for CVD, and a greater proportion of men than of women had all five metabolic syndrome components. The complete follow-up data from the OMEGA study will provide much-needed information to guide treatment in patients with hypertension and the metabolic syndrome. (Hypertens Res 2008; 31: 2011-2017).
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PMID:OMEGA study: design, baseline data, metabolic syndrome prevalence in a large-scale observational study of hypertensive patients: The Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement study. 1909 72


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