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

The major challenge for the treatment of hypertensive patients with type 2 diabetes is to achieve the uniformly recommended blood pressure goal of 130/80 mmHg, and 120/75 mmHg in proteinuric patients. Such low target blood pressure levels require the administration of multiple drugs. Angiotensin receptor blockers and the combination of angiotensin receptor blockers with diuretics fulfil the criteria to lower blood pressure effectively with a placebo-like side-effect profile. Beyond pressure control, clinical prospective trials have documented that it does matter what kind of antihypertensive agent is used to control blood pressure. Large-scale follow-up trials have documented blood pressure independent effects of angiotensin receptor blocker on cardiac [left-ventricular hypertrophy (LVH), congestive heart failure] and renal protection (proteinuria, chronic renal failure). Of note, in these trials, angiotensin receptor blockers have been combined with diuretics, and most of the included patients have been on combination therapy comprising two to four antihypertensive agents. In addition to the combination of an angiotensin receptor blocker with a diuretic, the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor appeared to be most effective in reducing proteinuria, attenuating chronic renal failure and treating congestive heart failure.
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PMID:Optimizing therapeutic strategies to achieve renal and cardiovascular risk reduction in diabetic patients with angiotensin receptor blockers. 1583 71

Hypertension and proteinuria are risk factors for renal disease progression. There is clear evidence that pharmacological blockade of the RAS with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows down the progression of renal disease in diabetic and non diabetic nephropathies, a beneficial effect not related to blood pressure control. However, not all patients respond similarly to these treatments. Some patients exhibit a significant beneficial response while others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI, which are unable to block completely the formation of AII, some generation of AII is produced via other non ACE pathways. In the search of new alternatives that could improve the antiproteinuric and nephroprotective effects of RAS blockers, the association of ACEI and ARB might prove to be useful. ARB produces a complete blockade of the RAS and stimulates the vasodilating and non-proliferative actions of AII via the AT-2 receptor. Furthermore, ACE inhibitors but not ARB; inhibit the metabolism of kinins, which increases the level of bradykinin, a potent vasodilator. Recently, several authors have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone in spite of a similar effect on blood pressure. A recent study also has demonstrated that this more marked antiproteinuric effect is associated with a less progression of renal disease in primary, non diabetic nephropathies. Furthermore, at least two studies have shown that, treatment with ARB postpones end-stage renal disease and reduces the rate of decline in renal function in patients with type 2 diabetes and nephropathy, but until now, there is not any clear evidence of a superior beneficial effect of dual blockade versus maximal recommended dose of ARB regarding renal progression in type 2 diabetic nephropathy, which is the most frequent cause of end stage renal disease. Long-term clinical trials are needed and encouraged to further establish the significant role of dual blockade in renal protection particularly in diabetic nephropathy.
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PMID:The reno-protective effect of the dual blockade of the renin angiotensin system (RAS). 1585 85

An aggressive global approach to screening and to the management of the metabolic syndrome is recommended to slow the growth of the syndrome throughout the United States. Prevention should begin in childhood with healthy nutrition, daily physical activity, and annual measurement of weight, height, and blood pressure beginning at 3 years of age. Such screenings will identify cardiovascular risk factors early, allow the health care provider to define global cardiovascular risk with the COSEHC Cardiovascular Risk Assessment Tool, and allow treatment of each risk factor. Lifelong lifestyle modifications and pharmacologic therapy will be required in most patients. Antihypertensive therapy for these patients should begin with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker unless a compelling indication for another drug is present. Metformin should be considered the first drug for glucose control in the patient with type 2 diabetes. A statin should be used initially for hyperlipidemia unless contraindicated. Combinations of antihypertensive, antiglycemic, and lipid-lowering agents will often be required.
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PMID:Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome in the southeastern United States, part II: treatment recommendations for management of the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome. 1595 71

Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-alpha. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis.
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PMID:Inflammation and the etiology of type 2 diabetes. 1599 Dec 54

Type 2 diabetes mellitus is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Many risk factors, including the metabolic syndrome, have been implicated in its development. Even in high-risk individuals, type 2 diabetes is a preventable disease. Diet and exercise have been consistently shown to decrease the incidence of diabetes in large randomized controlled studies. Additionally, new-onset diabetes was reduced by several oral pharmacologic anti-diabetic agents including metformin, acarbose and troglitazone in randomized trials which studied patients with impaired glucose tolerance. More interestingly, multiple large prospective studies have also reported a reduction in the development of type 2 diabetes in patients treated with anti-hypertensive agents, predominantly angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we will discuss some of these important trials and the speculative mechanisms whereby those medications prevent type 2 diabetes. Such observations, if proven to be true, may represent preventive strategies which can be considered in patients with pre-diabetic conditions such as the metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure or other risks for the development of type 2 diabetes.
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PMID:Strategies to prevent type 2 diabetes. 1600 80

This paper aims at comparing two meta-analyses of clinical trials having investigated the effect of the inhibition of the renin-angiotensin system either with an angiotensin converting enzyme inhibitor (ACEI) or with a selective angiotensin receptor blocker (ARB) on the incidence of new cases of type 2 diabetes mellitus in subjects with arterial hypertension or with congestive heart failure. The protection appears similar with ACEIs in six trials in a total of 24.623 patients (hazard ratio: 0.77; CI 95% 0.72-0.81; p < 0.00001 and with ARBs in five trials in a total of 14.344 patients (hazard ratio: 0.79; CI 95% 0.73-0.85; p < 0.00001). It is consistent whatever the comparator, a thiazide diuretic agent, a beta-blocker, a dihydropyridine calcium channel blocker or a placebo. The large ongoing ONTARGET controlled study will allow a direct comparison between an ACEI, ramipril, and an ARB, telmisartan, and will also investigate the potential benefit of a combined treatment with both drugs. The inhibition of the renin-angiotensin system should be considered among pharmacological strategies of prevention of type 2 diabetes mellitus.
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PMID:[Similar reduction in new cases of type 2 diabetes with angiotensin receptor blocker and ACE inhibitor: comparison of meta-analyses of prospective randomised trials]. 1603 5

Diabetes mellitus, arterial hypertension, smoking are major stroke risk factors. The role of hypercholesterolemia in stroke has not been established yet. In patients with type 2 diabetes mellitus there is evidence that intensive glucose lowering therapy diminishes the risk of microvascular complications. In all patients with stroke or transient ischemic attack (TIA), blood pressure should be lowered irrespectively of the baseline level with either diuretics, angiotensin converting enzyme (ACE) inhibitors, beta-blockers, or calcium antagonists. The role of angiotensin II (AT2) receptor blockers has not been established so far. In general terms a global approach to management of patients with vascular risk factors should be developed. An extended follow-up of randomised trials on preventive therapy should be completed. Controlled trials comparing angiotensin receptor blockers with ACE inhibitors should be started. Further research may focus on the new lipid lowering agents, and on the comparison of single lipid lowering agent vs. combinations in stroke prevention. These efforts should help in finding the best vasoprotective strategy in stroke prevention.
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PMID:Antihypertensive and lipid lowering treatment in stroke prevention: current state and future. 1607 57

Activation of the renin-angiotensin system has a pivotal role in the pathogenesis of diabetic complications. However, recent evidence suggests that it may also contribute to the development of diabetes itself. In the endocrine pancreas, all the components of an active renin-angiotensin system are present, which modulate a range of activities including local blood flow, hormone release and prostaglandin synthesis. In both types 1 and 2 diabetes, there is an up-regulation of its expression and activity in the endocrine pancreas. Whether these changes have a direct pathogenetic role or reflect a response to local stress or tissue injury remains to be established. Angiotensin-mediated increases in oxidative stress, inflammation and free fatty acids levels potentially contribute to beta-cell dysfunction in diabetes. In addition, activation of the renin-angiotensin system appears to potentiate the action of other pathogenic pathways including glucotoxicity, lipotoxicity and advanced glycation. In experimental models of type 2 diabetes, blockade of the renin-angiotensin system with angiotensin converting enzyme inhibitors or angiotensin receptor antagonists results in the improvement of islet structure and function. Moreover, the incidence of de novo diabetes appears to be significantly reduced by blockade of the renin-angiotensin system in clinical studies. At least two large controlled trials are currently underway to study the role of renin-angiotensin system in the development of diabetes. It is hoped that these studies will demonstrate the true potential of the blockade of the renin-angiotensin system for the prevention of diabetes.
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PMID:Role of the renin-angiotensin system in the endocrine pancreas: implications for the development of diabetes. 1619 40

Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system. Such changes in microalbuminuria have not been observed when beta-blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine the effects of different beta-blockers on changes in albuminuria in the presence of renin-angiotensin system blockade. Participants with hypertension and type 2 diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol (n=498) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Blinded medication was titrated to achieve target blood pressure, with a-5 month follow-up period. The current analysis examined microalbuminuria, using spot urine albumin:creatinine, in participants who had values at screening and trial end. A greater reduction in microalbuminuria was observed for those randomized to carvedilol (-16.2%Delta; 95% confidence interval, -25.3, -5.9; P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of 431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal (68% carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study (P=0.004). Beta-blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade. These differences cannot be explained by effects on blood pressure or alpha1-antagonism but may relate to antioxidant properties of carvedilol.
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PMID:Differential effects of beta-blockers on albuminuria in patients with type 2 diabetes. 1628 77

Direct and indirect costs related to the treatment of hypertension are estimated at nearly $60 billion annually. Short- and long-term costs of healthcare utilization and treatment are, therefore, important considerations in selection of antihypertensive therapy. Studies of patients with hypertension and type 2 diabetes have shown that treatment with angiotensin receptor blockers (ARBs) can reduce healthcare costs as a result of a decreased incidence of end-stage renal disease and other clinical end points. ARBs also increase survival in these patients. Cost savings have also been reported in patients with heart failure as a result of reductions in office and emergency department visits, hospital admissions, and hospital stays.
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PMID:Angiotensin receptor blockers: impact on costs of care. 1630 Apr 56


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