Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular and renal diseases in diabetes stem from an accelerated form of atherosclerosis in both small and large blood vessels. Diabetic nephropathy is a clinical hallmark of microangiopathy and often leads to end-stage renal failure. Significantly, microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in both the diabetic and non-diabetic population. In diabetic patients, it is also strongly associated with proliferative retinopathy, neuropathy and hypertension. Effective blood pressure reduction in patients with type 2 diabetes and diabetic nephropathy is known to reduce albuminuria, delay the progression of diabetic nephropathy, postpone renal failure and improve survival. These benefits have been demonstrated with a variety of blood pressure-lowering agents, including beta-blockers, calcium channel blockers, diuretics and angiotensin-converting enzyme (ACE) inhibitors. Less is known about the renal effects of the newest class of antihypertensive agents, the angiotensin II receptor antagonists (AIIRAs). Irbesartan is an AIIRA that provides antihypertensive efficacy comparable to ACE inhibitors but with superior tolerability. The PRogram for Irbesartan Mortality and morbidity Evaluations (PRIME) is an important morbidity and mortality program encompassing the Irbesartan Diabetic Nephropathy Trial (IDNT) and the IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients (IRMA II) study. PRIME is evaluating the effects of irbesartan in preventing diabetic nephropathy and end-stage renal failure and in reducing cardiovascular events in high-risk hypertensive patients with type 2 diabetes. The trials were completed at the end of 2000.
 ...
PMID:Hypertension and diabetes: the scope of the problem. 1146 14

Last year, in 2001, the results of several major clinical trials have been published, concerning hypertensive patients with type 2 diabetes (IRMA, RENAAL and IDNT studies) and patients with previous strokes. Angiotensin II antagonists (irbesartan and losartan) are able to reduce the rate of progression of diabetic nephropathy in hypertensive patients with type 2 diabetes. This preventive effect occurs independently of the stage of renal dysfunction (early stage in IRMA, patent nephropathy in RENAAL and advanced nephropathy in IDNT). The PROGRESS study shows that the decrease in blood pressure, in response to an ACE inhibitor/diuretic bitherapy (perindopril/indapamide), in patients with previous minor stroke or transient ischaemic attack, reduces significantly the risk of recurrent stroke.
 ...
PMID:[The best of 2001. Arterial hypertension]. 1190 4

Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
 ...
PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

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.
 ...
PMID:Renal and cardiovascular protection in type 2 diabetes mellitus: angiotensin II receptor blockers. 1246 18

Blood pressure reduction and intensive antihypertensive treatment are effective in reducing both microvascular and macrovascular complications in type 2 diabetes. Blood pressure target levels < 130/85 or 130/80 mmHg are now recommended. Antagonism of the renin-angiotensin-aldosterone system seems to be an important goal in the treatment of hypertension and diabetes-related complications. The renoprotective role of angiotensin-converting enzyme (ACE)-inhibitors has been well documented in type 1 diabetes; in type 2 diabetes ACE-inhibitors have been deemed more effective than other traditional drugs in reducing the onset of overt nephropathy in microalbuminuric patients (secondary prevention) but not in reducing renal dysfunction in patients with clinical proteinuria (tertiary prevention). Recently, four large trials performed on type 2 diabetes showed that angiotensin II receptor blockers (ARBs) prevent the development of clinical proteinuria in microalbuminuric patients (IRMA and MARVAL studies) and delay the progression of nephropathy towards end-stage renal failure in patients with overt nephropathy (IDNT and RENAAL studies). Moreover, ARBs have been deemed more effective in reducing hospitalizations for heart failure compared to placebo (IDNT and RENAAL studies) and in reducing cardiovascular morbidity and mortality compared to conventional therapy (LIFE study) in type 2 diabetes. In conclusion, ARBs are effective in preventing and delaying renal damage in type 2 diabetes. Thus, the recent guidelines for the prevention and treatment of diabetic nephropathy state that ACE-inhibitors are the first-choice drugs in type 1 diabetes while ARBs are considered as the first-choice drugs in secondary prevention, the same as ACE-inhibitors, and are the unique first-choice drug in tertiary prevention of end-stage renal failure in type 2 diabetes. Finally, ACE-inhibitors and ARBs are both first-choice drugs in cardiovascular prevention in type 2 diabetes.
 ...
PMID:[The role of angiotensin II AT1-receptor antagonists in renal and cardiac protection in type-2 diabetes mellitus]. 1278 55

The increased activity of the renin-angiotensin-aldosterone system (RAAS) is an important pathogenetic factor in the development of nephropathy in diabetic patients. The damaging factor of this system is the end-product, angiotensin II, and the damaging effects are vasoconstriction, increase of aldosterone secretion, growth, fibrosis, thrombosis, inflammation and oxidation. Theoretically, on this basis, blockade of the RAAS should have a beneficial effect on the development of diabetic nephropathy. The main goal in the treatment of diabetic nephropathy is control of the glycaemic status and aggressive antihypertensive therapy, primarily with RAAS-blocking agents. It was demonstrated recently that angiotensin II receptor blockers (ARBs) have a slowing effect on the progression of diabetic nephropathy (RENAAL and IDNT trials) or on the development of proteinuria (IRMA) in type 2 diabetes. These effects are specific and independent of the decrease in blood pressure. Theoretically, the combination of an angiotensin-converting enzyme inhibitor (ACEI) and an ARB can lead to a more complete blockade of the RAAS. A new study (ONTARGET) has now started to investigate whether treatment with a combination of an ACEI and an ARB has a more potent beneficial effect on the cardiovascular events and the nephropathy in type 2 diabetic patients as compared with separate treatment with the two agents.
 ...
PMID:Treatment of diabetic nephropathy with angiotensin II blockers. 1281 61

Irbesartan (Avapro, Aprovel) is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily administration of irbesartan provided 24-hour control of blood pressure (BP). In patients with mild-to-moderate hypertension irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than valsartan in terms of absolute reduction in BP and response rates. Irbesartan produced a greater reduction in diastolic BP at trough than once-daily losartan, but had a smaller effect than olmesartan; the reduction in systolic BP achieved with irbesartan was similar or greater than that with losartan and similar to that seen with olmesartan. The combination of irbesartan with hydrochlorothiazide produced additive effects on BP reduction. Irbesartan also induced regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy. In two large studies (IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients [IRMA 2] and the Irbesartan Diabetic Nephropathy Trial [IDNT]) irbesartan exerted a renoprotective effect in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. The renoprotective effect was at least partly independent of the BP-lowering effect. In the IRMA 2 trial, the proportion of patients progressing to overt nephropathy was significantly lower for recipients of irbesartan 300mg once daily than placebo. In patients with overt nephropathy in the IDNT, irbesartan 300mg once daily provided significantly greater renoprotection than amlodipine 10mg once daily or placebo. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan is well tolerated in hypertensive patients, including those with type 2 diabetes and incipient or overt nephropathy. The overall incidence of adverse events with irbesartan was similar to that with placebo. Irbesartan was associated with a lower incidence of cough than enalapril and was not associated with ankle oedema or with any clinically significant drug interactions. In conclusion, irbesartan is a well tolerated and effective antihypertensive agent. It also slows the progression of renal disease in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. Thus, irbesartan is a valuable agent in the management of patients with these indications.
 ...
PMID:Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. 1510 93

Angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) are a class of antihypertensive drugs that are generally considered comparable to ACE inhibitors in the prevention of heart and kidney failure. However, these two classes of agents do interfere in different stages of the renin-angiotensin system. In patients with type 2 diabetes mellitus, advantages for ARBs over conventional (non-ACE inhibitor) therapy on progression from micro- to macroalbuminuria and overt nephropathy and end-stage renal disease have been shown in clinical trials. In patients with type 2 diabetes and end-stage renal disease, the need for dialysis and/or transplantation results in the use of major healthcare resources. This paper reviews the available economic evidence on treatment with ARBs in type 2 diabetic patients with advanced renal disease.Within-trial analytic and Markov model economic evaluations of the RENAAL (Reduction of Endpoint in Non-insulin dependent diabetes mellitus with Angiotensin II Antagonist Losartan), IDNT (Irbesartan Diabetic Nephropathy Trial) and IRMA (IRbesartan in type 2 diabetes with MicroAlbuminuria)-2 studies suggest that treatment with ARBs in patients with type 2 diabetes with overt or incipient nephropathy confers health gains and net cost savings compared with conventional (non-ACE inhibitor) therapy. For reimbursement and reference pricing decisions, there is a need for a head-to-head comparison of an ACE inhibitor with ARBs to model all possible costs and effects of ACE inhibitors and ARBs. This will result in a proper pharmacoeconomic outcome, where both types of drugs can be compared for healthcare decisions.
 ...
PMID:Pharmacoeconomics of angiotensin II antagonists in type 2 diabetic patients with nephropathy: implications for decision making. 1676 1

Beneficial effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin type 1 receptor (AT1) blockers in patients with cardiovascular and renal diseases have been clearly demonstrated in numerous large outcomes studies. In patients with heart failure (HF), ACEI have been shown to reduce overall mortality, mortality from cardiovascular causes, to increase life expectancy, as well as to preserve the renal function (CONSENSUS, SAVE, TRACE, AIRE, AIREX, CATS trials). In addition, in the PROGRESS study ACEI substantially decreased the risk of stroke and transient ischemic attacks in patients with cerebrovascular disorders. The HOPE and EUROPA studies confirmed that long term therapy with ACEI provides significant survival benefit in patients with broad range of atherosclerotic cardiovascular diseases. After these large and well designed clinical studies, ACEI have become standard therapy for routine secondary prevention in all patients with cardiovascular diseases, unless contraindicated. AT1 receptor blockers have been recently added to the cardiovascular therapeutic armamentarium. They are believed to provide additional protection by inhibition of locally synthesized angiotensin II on the level of AT1 receptor. The ELITE II, ValHeFT and CHARM studies have shown that AT1 receptor blockers are equally effective as ACEI in reduction of mortality and morbidity in patients with HF. Importantly, they may be used together with ACEI, or as alternative treatment in ACEI intolerant patients. Renal protection is another important effect of both ACEI and AT1 blockers that has been confirmed in several large clinical trials. The North American Microalbuminemia Study group and EUCLID group demonstrated significant reduction in progression of diabetic nephropathy in patients with insulin dependent diabetes mellitus (IDDM) treated with ACEI. AT1 receptor blockers are mainly studied in the non-insulin dependent diabetes mellitus (NIDDM) nephropathy. Four recent clinical trials (IRMA-2, DETAIL, RENAAL and IDNT) examined the effect of AT1 receptor blockers in patients with NIDDM nephropathy. These studies confirmed the beneficial effect of AT1 receptor blockers in patients with NIDDM nephropathy that was extended beyond the blood pressure reduction. Ongoing studies (ONTARGET, TRANSCEND and PROTECTION) should provide us with additional insights about cardiovascular, renal and other end-organ protective effects of these therapeutics.
 ...
PMID:Role of renin angiotensin system inhibitors in cardiovascular and renal protection: a lesson from clinical trials. 1750 19

Diabetic nephropathy is a leading cause of renal failure requiring replacement therapy. Diabetic nephropathy is typically characterized by persistent microalbuminuria progressing to nephrotic syndrome, a progressive decline in glomerular filtration rate, and hypertension. Diabetic nephropathy prevention strategies may involve early angiotensin-converting enzyme (ACE) inhibitor treatment and the control of diabetes to reduce glomerular hypertension and hyperfiltration. Treatment strategies include the use of ACE inhibitors or angiotensin receptor blockers (ARBs), and cholesterol-lowering agents. Early intervention is key to the prevention of more severe renal outcomes. Although intensive and early control of blood pressure (BP) is key to renoprotection, the class of antihypertensive has an important bearing on outcome. There is evidence for the efficacy of ARBs in preventing the progression from microalbuminuria to overt nephropathy (urine protein excretion >500 mg/day) from the IRbesartan in patients with diabetes and MicroAlbuminuria (IRMA 2) Study using irbesartan and the INcideNt to OVert: Angiotensin II receptor blocker, Telmisartan, Investigation On type 2 diabetic Nephropathy (INNOVATION) Study using telmisartan. For the management of overt nephropathy, the findings of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) demonstrate that losartan and irbesartan, respectively, reduce the time to doubling of serum creatinine levels and development of end-stage renal disease.
 ...
PMID:Slowing the progression of kidney disease in patients with diabetes. 2040 36


1 2 Next >>