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

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

Angiotensin-converting enzyme (ACE) inhibitors have favourable effects on hypertension and diabetic nephropathy, but persistent use may result in incomplete blockade of the renin-angiotensin system. Long-term effects of dual blockade using the ACE inhibitor lisinopril and the long-acting angiotensin II receptor blocker (ARB) telmisartan on blood pressure and albumin excretion rate (AER) were evaluated. Patients with type 2 diabetes mellitus, hypertension (systolic blood pressure [SBP] >or=140 mmHg or diastolic blood pressure [DBP] >or=90 mmHg) and microalbuminuria (AER 30-300 mg/24h) received 20mg of lisinopril or 80 mg of telmisartan once a day for 24 weeks. Patients were then randomised to continuing treatment with the respective monotherapy or with lisinopril plus telmisartan for a further 28 weeks. Significant (P<0.001) declines in SBP (11.1 mmHg versus 10.0 mmHg), DBP (5.6 mmHg versus 5.3 mmHg) and AER (98 mg/24 h versus 80 mg/24 h) were achieved with lisinopril (n=95) or telmisartan (n=97), respectively, after 24 weeks. Subsequent treatment with lisinopril plus telmisartan for 28 weeks resulted in further significant reductions (P<0.001) in SBP, DBP and AER compared with either monotherapy. All treatments were well tolerated. Lisinopril plus telmisartan thus provides superior blood pressure and AER control than either monotherapy. We conclude that use of dual blockade may provide a new approach to prevention of diabetic nephropathy in patients with type 2 diabetes, hypertension and microalbuminuria.
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PMID:Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension. 1611 44

Type 2 diabetes mellitus has reached epidemic proportions and diabetic nephropathy is the leading cause of end-stage renal disease. The metabolic syndrome constitutes a milieu conducive to tissue redox stress. This loss of redox homeostasis contributes to renal remodeling and parallels the concurrent increased vascular redox stress associated with the cardiometabolic syndrome. The multiple metabolic toxicities, redox stress and endothelial dysfunction combine to weave the complicated mosaic fabric of diabetic glomerulosclerosis and diabetic nephropathy. A better understanding may provide both the clinician and researcher tools to unravel this complicated disease process. Cellular remodeling of podocyte foot processes in the Ren-2 transgenic rat model of tissue angiotensin II overexpression (TG(mREN-2)27) and the Zucker diabetic fatty model of type 2 diabetes mellitus have been observed in preliminary studies. Importantly, angiotensin II receptor blockers have been shown to abrogate these ultrastructural changes in the foot processes of the podocyte in preliminary studies. An integrated, global risk reduction, approach in therapy addressing the multiple metabolic abnormalities combined with attempts to reach therapeutic goals at an earlier stage could have a profound effect on the development and progressive nature to end-stage renal disease and ultimately renal replacement therapy.
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PMID:Renal redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and diabetic nephropathy: paying homage to the podocyte. 1621 Aug 38

Renal complications resulting from type 2 diabetes mellitus are costly and common. Finding optimal therapy is important for the prevention and management of diabetic nephropathy. Research has focused on antihypertensive agents that modify the renin-angiotensin-aldosterone system. Because of their effects on the glomerulus, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have been studied as interventions at various stages of diabetic nephropathy. The ACE inhibitors may delay the progression to microalbuminuria and then clinical albuminuria. The ARBs decrease albuminuria in patients with microalbuminuria and decrease adverse renal events, specifically the progression to end-stage renal disease in patients with clinical albuminuria and hypertension. Limited data suggest that combination therapy with ACE inhibitors and ARBs may slow the progression of microalbuminuria to clinical albuminuria. Because of the variability in degree of albuminuria evaluated and in study designs (numbers of patients, study duration, drug dosages, and outcomes measured), a detailed review of the available literature about ACE inhibitors and ARBs in the prevention or treatment of diabetic nephropathy may provide insight to clinicians.
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PMID:Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for prevention and treatment of nephropathy associated with type 2 diabetes mellitus. 1623 22

The angiotensin II receptor antagonist eprosartan is approved for the treatment of essential hypertension and may be administered using a convenient once-daily regimen. The drug is a well tolerated and effective antihypertensive agent with benefit in the secondary prevention of cerebrovascular events, independent of blood pressure (BP)-lowering effects. Eprosartan has a low potential for serious adverse events and has not been associated with clinically significant drug interactions, establishing it as a promising agent for combination antihypertensive strategies. Unlike ACE inhibitors such as enalapril, eprosartan does not have a tendency to cause persistent nonproductive cough. Accordingly, eprosartan represents a useful therapeutic option in the management of patients with hypertension, including those who have had a stroke and those with co-morbid type 2 diabetes mellitus.
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PMID:Eprosartan: a review of its use in the management of hypertension. 1626 4

We planned the INNOVATION study to determine whether telmisartan, an angiotensin-2-receptor blocker, delays the progression of renal disease from incipient nephropathy to overt nephropathy in hypertensive or normotensive Japanese patients with type 2 diabetes mellitus. The INNOVATION study is a randomized, double-blind, placebo-controlled trial. Eligible patients must have incipient nephropathy (defined as a urinary albumin to creatinine ratio of 100-300 mg/g creatinine) and a serum creatinine concentration of < 1.5 mg/dl for men and < 1.3 mg/dl for women. Patients who need treatment with angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors are excluded. Eligible patients are randomly assigned to three groups: telmisartan titrated to 40 mg; telmisartan titrated to 80 mg; or placebo. The primary endpoint is the time from baseline visit to first detection of overt nephropathy (defined by a urinary albumin to creatinine ratio that is > 300 mg/g creatinine and 30% higher than the baseline on at least two consecutive visits). A total of 1855 patients have been enrolled from 160 study centres. In 527 randomized patients (28.4% of the enrolled patients), mean (SD) urinary albumin to creatinine ratio and serum creatinine concentration at baseline were 173.3 (47.2) mg/g creatinine and 0.78 (0.19) mg/dl. Sixty-eight per cent of the patients had hypertension at baseline. Mean (SD) systolic and diastolic blood pressures at baseline were 137.1 (14.6) and 77.5 (10.3) mmHg. The INNOVATION study will determine whether telmisartan, an angiotensin II receptor blocker, provides clinical benefits in hypertensive or normotensive patients with diabetes mellitus and diabetic nephropathy.
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PMID:The telmisartan renoprotective study from incipient nephropathy to overt nephropathy--rationale, study design, treatment plan and baseline characteristics of the incipient to overt: angiotensin II receptor blocker, telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study. 1637 86

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

The prevalence of diabetes mellitus is increasing worldwide. Among other complications, diabetes is associated with the risk of coronary heart disease (CHD) that is thought to be equal to the risk of CHD in subjects without diabetes with previous myocardial infarction. Studies have shown that CHD risk factors start to increase long before the onset of clinical diabetes. Furthermore, the risk factors that are present in prediabetic individuals are also components of the highly prevalent metabolic syndrome. This suggests that treatment of CHD risk factors may effectively reduce the incidence of type 2 diabetes. Lifestyle interventions have proved effective in preventing the onset of type 2 diabetes in subjects with impaired glucose tolerance. A number of post hoc studies have reported consistent reductions in the incidence of type 2 diabetes in hypertensive patients treated with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). As a result of these positive data, ongoing prospective studies are investigating whether antihypertensive agents prevent or delay the onset of diabetes in patients at risk. Telmisartan, a selective oral ARB that is indicated for first-line therapy of essential hypertension, may provide improved tolerability compared with ACE inhibitors. Therefore, the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program is investigating the effectiveness of telmisartan in the prevention or delay of type 2 diabetes. The program comprises ONTARGET and the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND).
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PMID:Risk constellations in patients with the metabolic syndrome: epidemiology, diagnosis, and treatment patterns. 1656 45

The importance of renal function as both a marker of and risk factor for cardiovascular disease is increasingly recognized. This link is apparent even in the earliest stages of renal dysfunction, at levels that are conventionally considered "normal." These findings are of considerable importance, given the prevalence of high-normal levels of albuminuria (i.e., 10 to 20 mg/L) in the general population. There is also a close link between the progression of albuminuria and the development of insulin resistance and type 2 diabetes mellitus, such that kidney disease--far from being simply a consequence of the metabolic syndrome--may be considered a component of it. It may be hypothesized that minor derangements of renal function, such as microalbuminuria or reduced glomerular filtration rate, can lead to dysfunction of the endothelium, with the consequence of sensitizing the vasculature to the injurious effects of hypertension, dyslipidemia, and other risk factors. The renin-angiotensin system (RAS) is highly activated in patients with the metabolic syndrome, and this presumably is also true for the intrarenal RAS systems. Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are known to reduce the progression of renal damage. Still to be resolved, however, is the optimal dosage; several recent studies indicate that the dosage required for maximal blood pressure reduction is insufficient to provide maximal renoprotection.
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PMID:Heart and kidney: fatal twins? 1656 46

Management of hypertension is the mainstay of prevention and treatment of diabetic renal disease; evidence suggests that tight blood pressure control slows renal disease progression in established diabetic nephropathy. Inhibition of the renin-angiotensin-aldosterone system (RAAS) has renoprotective effects over and above those achieved by lowering systemic blood pressure. To date, however, no long-term study using hard end points has directly compared current mechanisms for RAAS inhibition, angiotensin II receptor blockade (ARB) and angiotensin-converting enzyme (ACE) inhibition. This issue was addressed in the recently published Diabetics Exposed to Telmisartan and Enalapril (DETAIL) study, a head-to-head comparison of telmisartan and enalapril in 250 patients with hypertension and type 2 diabetes mellitus and early-stage nephropathy. After 5 years' treatment, change in glomerular filtration rate (GFR), the primary efficacy end point, was equivalent in the 2 treatment groups, as were all secondary end points. The expected steep decline in GFR in the first year was followed by a lesser decrease in the second year and then almost complete stabilization of renal function at > or =3 years. Over 5 years, no patient went into end-stage renal disease or required dialysis. There were also no increases in albumin excretion rate, nor was there an increase in creatinine beyond 200 mumol/L. Incidence of cardiovascular morbidity and mortality was extremely low in both treatment groups, a remarkable outcome given that almost 50% of patients had evidence of cardiovascular disease at randomization. Inhibition of the RAAS should play a major part in management of patients with type 2 diabetes with nephropathy, for which both telmisartan and enalapril provide long-term renoprotection.
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PMID:Prevention of loss of renal function over time in patients with diabetic nephropathy. 1656 47

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