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

Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.
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PMID:Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria. 1548 18

Irbesartan (Aprovel) belongs into the new group drugs for the cardiovascular system which exert an antagonistic effect at the level of angiotensin II, but experimental pilot studies as well as clinical studies draw also attention to the possible therapeutic potential of AT1 receptor blockers in the treatment of chronic heart failure. Irbesartan has a marked antihypertensive effect as is apparent from a recent clinical study in 139 patients with mild and moderate hypertension--implemented in the Czech Republic. Twelve-week treatment with Irbesartan led to a marked drop of the systolic and diastolic blood pressure (159.2 +/- 14 vs. 137 +/- 13 mmHg/99.2 +/- 7 vs. 85.3 +/- 7 mmHg, p < 0.01). A very favourable therapeutic effect was recorded in this investigation also in 24-hour monitoring of the blood pressure. The use of irbesartan in patients with arterial hypertension has according to other studies also a favourable effect on organ complications of hypertension and diabetes (regression of left ventricular hypertrophy, reduction of albuminuria). Irbesartan may prove due to its favourable effect a suitable alternative in conditions associated with intolerance of ACE-inhibitors in patients with moderate and severe forms of arterial hypertension, in chronic heart failure and in diabetic nephropathy.
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PMID:[Irbesartan in the treatment of arterial hypertension]. 1564 39

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, with target BP < 130/80 mmHg being recommended. Angiotensin-converting enzyme inhibitors were found to be more effective than the other traditional agents in reducing the onset of clinical proteinuria in individuals with both type 1 and type 2 diabetes and incipient nephropathy. However, small trials on patients with type 2 diabetes and overt nephropathy failed to demonstrate a specific renoprotective role for this class of drugs. The aim of the Program for Irbesartan Mortality and Morbidity Evaluation was to ascertain whether angiotensin II receptor blockers are effective in both preventing the development of clinical proteinuria and delaying the progression of nephropathy in type 2 diabetes. The Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA) Study showed that, as compared with conventional therapy, irbesartan is better at preventing the development of clinical proteinuria and at restoring normoalbuminuria for comparable BP control in patients with incipient nephropathy. The Irbesartan Diabetic Nephropathy Trial showed that irbesartan is more effective than traditional antihypertensive therapies in reducing the progression toward ESRD in patients with type 2 diabetes and overt nephropathy regardless of changes in BP. Moreover, secondary analysis of the Irbesartan Diabetic Nephropathy Trial showed that the achieved systolic pressure as well as baseline and current proteinuria significantly predict renal outcomes. In conclusion, the results of the Program for Irbesartan Mortality and Morbidity Evaluation demonstrate that irbesartan significantly prevents the development of clinical proteinuria in individuals with microalbuminuria and delays the progression of nephropathy in individuals with proteinuria. Moreover, the renoprotective effects of irbesartan go beyond its effect on BP.
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PMID:Prevention and treatment of diabetic nephropathy: the program for irbesartan mortality and morbidity evaluation. 1593 34

Hypertension is a powerful risk factor for cardiovascular (CV) morbidity and mortality; therefore, blood pressure (BP) lowering plays a central role in reducing the cardiovascular complications of hypertension, including stroke. Recent outcomes studies--Losartan Intervention For Endpoint reduction in hypertension, Reduction of Endpoints in Non-insulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan, and the Irbesartan Type 2 Diabetic Nephropathy Trial--suggest that some angiotensin II antagonists are associated with CV and renal effects beyond their ability to lower BP in patients with hypertension or diabetic nephropathy and may play a role in the prevention of new-onset type 2 diabetes. Angiotensin II antagonists are associated with a wide variety of vascular, cardiac, and renal effects, as well as molecule-specific effects independent of those induced by the angiotensin-I receptor. These actions may offer a mechanistic explanation for the outcome benefits observed in patients with hypertension or diabetic nephropathy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers may also have effects that are not completely explained by differences in the antihypertensive response to these agents, but the evidence is less robust. Collectively, these findings suggest that management of patients with hypertension, with or without diabetes or renal disease, should no longer be viewed as simply a matter of correcting elevated BP. Antihypertensive agents that possess CV benefits beyond their BP-reducing effects should be used to prevent the development of end-organ damage.
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PMID:Do angiotensin II antagonists provide benefits beyond blood pressure reduction? 1602 Apr 2

Type 2 diabetes is a chief cause of pathologies such as cardiovascular disease, nephropathy and retinopathy, and its prevalence is increasing worldwide. Development of renal disease can be slowed by tight glycaemic control and treatment of associated hypertension with angiotensin-converting enzyme inhibition, as The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study have demonstrated. Recent clinical trials have supported the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, resulting in the approval of new therapeutic indications in the US and Europe. The main goal of this review is to demonstrate how results from the Programme for Irbesartan Mortality and Morbidity Evaluation and other recent studies, based on the effects of renin-angiotensin system blockade, can be appropriate in clinical practice, thus displaying benefits of irbesartan therapy at any stage of renal disease in diabetics.
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PMID:An update of irbesartan and renin-angiotensin system blockade in diabetic nephropathy. 1608 46

There is a rising incidence and prevalence of ESRD as a result of diabetes, with poor outcome and growing costs. Recently, two large trials, the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL), showed that angiotensin receptor blockers (ARB) are more effective than traditional antihypertensive therapies at reducing progression toward ESRD in hypertensive patients with type 2 diabetes and overt nephropathy, regardless of changes in BP. The results of these two trials were used to compare the costs of ARB with those of renal replacement therapy (dialysis and renal transplantation) in an effort to establish whether ARB are cost-saving because they delay ESRD. Two different pharmacoeconomic approaches were used. With regard to the RENAAL trial, the number of ESRD days on losartan therapy as compared with the number of ESRD days on standard antihypertensive therapy was calculated, and the difference between the two was combined with the costs of ESRD. In the IDNT trial, Markov models were applied to assess the economic impact of irbesartan and to extrapolate future clinical and cost outcomes. Several economic analyses were performed in the United States and in European countries. Applying pharmacoeconomic models showed that treatment with ARB was associated with a greater improvement in life expectancy and lower total costs compared with amlodipine and standard antihypertensive therapy. Therefore, treating patients with type 2 diabetes, nephropathy, and hypertension with ARB is life- and cost-saving compared with traditional antihypertensive therapy.
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PMID:Economic evaluation of angiotensin receptor blockers in type 2 diabetes, hypertension, and nephropathy. 1656 46

Angiotensin II antagonists (AIIAs) were introduced to treat hypertension about 10 years ago. During this period they were evaluated not only in terms of efficacy and safety but also in several large studies with clinical outcomes. They are efficacious in all clinical forms of hypertension and are effective also in all ethnic groups. Cardiovascular and renal protection in proteinuric diabetic nephropathy beyond blood pressure reduction was proved in major clinical studies: Losartan Intervention For Endpoint reduction in hypertension study (LIFE), Reduction of Endpoint in Non-Insulin dependent Diabetes Mellitus with the AII Antagonist Losartan (RENAAL) and Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT). Their blood pressure independent protective effect is also mentioned by the blockade of AT1 receptor. As a class AIIs have a tolerability profile similar to placebo.
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PMID:Angiotensin II antagonists: clinical experience in the treatment of hypertension, prevention of cardiovascular outcomes and renal protection in diabetic nephropathy and proteinuria. 1676 99

The impact of irbesartan treatment on biomarkers of low-grade inflammation, endothelial dysfunction, growth factors, and advanced glycation end products (AGEs) during the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study was evaluated. IRMA 2 was a 2-year multicenter, randomized, double-blind trial in patients comparing irbesartan (150 or 300 mg once daily) versus placebo. The primary end point was onset of overt nephropathy. A subgroup (n = 269, 68%) was analyzed for biomarkers at baseline and after 1 and 2 years. High-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, fibrinogen, adhesion molecules, transforming growth factor-beta, and AGE peptides were assessed. Irbesartan treatment yielded significant changes in hs-CRP (based on generalized estimating equation regression coefficient) with a 5.4% decrease per year versus a 10% increase per year in the placebo group (P < 0.001). Fibrinogen decreased 0.059 g/l per year from baseline versus placebo's 0.059 g/l increase per year (P = 0.027). IL-6 showed a 1.8% increase per year compared with placebo's 6.5% increase per year (P = 0.005). Changes in IL-6 were associated with changes in albumin excretion (P = 0.04). There was no treatment effect on the other biomarkers. Irbesartan (300 mg once daily) reduces low-grade inflammation in this high-risk population, and this may reduce the risk of micro- and macrovascular disease.
Diabetes 2006 Dec
PMID:Irbesartan treatment reduces biomarkers of inflammatory activity in patients with type 2 diabetes and microalbuminuria: an IRMA 2 substudy. 1713 May 3

Microalbuminuria independently predicts increased cardiovascular risk in hypertensive patients, especially in those with concomitant diabetes or established cardiovascular disease. Drugs that target the renin-angiotensin-aldosterone system reduce microalbuminuria regardless of diabetic status. The Irbesartan in the Management of PROteinuric patients at high risk for Vascular Events was a multicenter, randomized, double-blind, placebo-controlled paralleled group study in which hypertensive patients with microalbuminuria and increased cardiovascular risk were randomized to 20 weeks treatment with ramipril plus irbesartan or to ramipril plus placebo. Patients discontinued or tapered previous antihypertensive therapy during a 14-day placebo lead-in period. Change in albumin excretion rate from baseline to week 20 was the primary end point. Adjusted week 20 baseline geometric ratios for ramipril plus irbesartan and ramipril plus placebo were not significantly different. Although differences in blood pressure reductions were observed between the two treatments, these changes did not affect microalbuminuria. More patients on dual therapy achieved target blood pressure goals at week 20 than with monotherapy. The incidence of adverse effects and treatment-related adverse effects was similar in both groups. Our results suggest that patients with cardiovascular risk and relatively low albumin excretion rates in early-stage disease may only require monotherapy with renin-angiotensin-aldosterone blocking agents.
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PMID:Treatment of microalbuminuria in hypertensive subjects with elevated cardiovascular risk: results of the IMPROVE trial. 1788 41

This post hoc analysis of the Irbesartan/Hydrochlorothiazide (HCTZ) Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of fixed-dose irbesartan/HCTZ in patients with isolated systolic hypertension. Adults with uncontrolled systolic blood pressure (SBP) (140-179 mm Hg; 130-179 mm Hg in type 2 diabetes) after 4 weeks or more of antihypertensive monotherapy once-daily treatment with placebo for 4-5 weeks, followed by HCTZ 12.5 mg for 2 weeks, irbesartan/HCTZ 150/12.5 mg for 8 weeks, and then irbesartan/HCTZ 300/25 mg for 8 weeks, in a prospective, multicenter, open-label, single-arm study. In patients with isolated systolic hypertension (n = 443) and the total study population (n = 736), irbesartan/HCTZ treatment for 16 weeks provided comparable mean blood pressure (BP) reductions from baseline (21.4/10.1 mm Hg vs 21.5/10.4 mm Hg; p < .001 vs baseline) and high SBP control rates (74% vs 77%). Patients with isolated systolic hypertension and concomitant type 2 diabetes experienced smaller BP reductions (17.9/8.7 mm Hg vs 22.9/10.7 mm Hg) and lower rates of SBP control (< 130 mm Hg, 47%) than those without diabetes (< 140 mm Hg, 87%). BP reductions from baseline and SBP control rates were similar across isolated systolic hypertension subgroups (> or = 65 vs < 65 years, sex, race, and metabolic syndrome status). Irbesartan/HCTZ was well tolerated, with drug-related adverse events (dizziness, < or = 3%; upper respiratory tract infection, < or = 2%) occurring with similar rates in the isolated systolic hypertension and total population. Fixed-dose irbesartan/HCTZ combination treatment provided effective and well-tolerated BP lowering in a diverse population of patients with isolated systolic hypertension.
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PMID:Irbesartan/hydrochlorothiazide for the treatment of isolated systolic hypertension: a subgroup analysis of the INCLUSIVE trial. 1939 19


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