Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the RAAS in development and maintenance of blood pressure is well established. In addition, the deleterious effects of angiotensin II on the heart, vasculature, and kidneys have been clearly defined. There seems to be a close relationship between endothelial dysfunction, insulin resistance (a precursor to diabetes and coronary artery disease) and angiotensin II. The signaling pathways for insulin in the vascular wall interacts with the angiotensin signaling, giving rise to potential mechanisms for development of diabetes and resulting harmful effects. A large number of clinical trials using ACE inhibitors or ARBs have shown significant reduction in secondary endpoints in the development of new onset of diabetes. Ongoing prospective studies involving ARBs (eg, the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research trial) and ACE inhibitors (eg, the Diabetes Re-duction Assessment with Ramipril and Rosiglita-zone Medication trial) are testing the ability of certain agents to prevent type 2 diabetes. In the meantime, it is important to recognize insulin resistance and metabolic syndrome as entities that increase the risk for cardiovascular disease. In addition to lifestyle modifications, managing endothelial dysfunction and protecting the vasculature will help prevent diabetes and cardiovascular disease.
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PMID:The renin angiotensin system as a therapeutic target to prevent diabetes and its complications. 1569 45

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

Antihypertensive drugs that inhibit the renin-angiotensin system (RAS) have been proposed to have additional benefits beyond their classic effects on the cardiovascular system, including reducing the risk of new-onset diabetes. Whether RAS inhibitors vary in ability to protect against new-onset diabetes is, however, unknown. The angiotensin II type 1 receptor (AT(1)) blocker telmisartan has been discovered to also activate the peroxisome proliferator-activated receptor-gamma (PPARgamma), an established antidiabetic drug target. In patients with hypertension and biochemical features of the metabolic syndrome, telmisartan has had beneficial effects on lipid and glucose metabolism. As a selective modulator of PPARgamma, telmisartan does not cause the side effects of fluid retention and weight gain associated with conventional thiazolidinedione ligands of PPARgamma. These observations raise the possibility that combined AT(1) receptor blockade and selective PPARgamma modulation with molecules such as telmisartan could provide greater protection from new-onset diabetes and cardiovascular disease than drugs that target either the RAS or PPARgamma alone. The cardioprotective and antidiabetic effects of telmisartan are being assessed in two large clinical trials, the ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular Disease (TRANSCEND).
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PMID:Beyond the classic angiotensin-receptor-blocker profile. 1858 Aug 62

The development of angiotensin II receptor blockers (ARB) as a new class of drugs for the management of hypertension has elicited the attention of many clinicians worldwide with the aim of improving blood pressure (BP) control as well as cardiovascular protection. Among ARB telmisartan has been shown to be characterised by an antihypertensive efficacy fully covering the 24-hour period, thereby allowing to antagonise the adverse effects of early morning BP rise on cardiovascular risk. Other specific effects of the drug are represented by its favourable metabolic profile (particularly on insulin sensitivity) and neutral effects on sympathetic cardiovascular function. These properties are coupled with cardioprotective effects, documented by the evidence that the drug: 1) is effective in favouring the regression of cardiac and vascular organ damage, 2) reduces arterial stiffness and improves vascular distensibility and 3) reverses the endothelial dysfunction typical of the hypertensive state particularly when complicated by renal failure, diabetes, obesity or metabolic syndrome. Several of these properties can account for the results of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), documenting the beneficial effects on the drug on cardiovascular morbidity and mortality.
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PMID:Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension. 1858 82

1. Epidemiological aspects: There is evidence that the pandemic of DM is entering a stabilization phase, with a slight downturn in the rates of ESRD attributed to DM in the United States. 2. New pathogenic and progression mechanisms of renal disease are proposed: 1) Intraglomerular hyperpressure with phenotypical cell changes, inducing TGF-beta activation; 2) Genetic polymorphisms, with candidate genes in chromosomes 18q, 3q, 7p and others; 3) Endothelial dysfunction as an injury initiating mechanism, demonstrated in the eNOS knockout rat; 4) Isoforms of PKC molecules that favor progression of nephropathy. 3. Importance of metabolic syndrome as a progression factor of chronic renal disease. 4. Increased CV risk in patients treated with thiazolidinediones (glitazones) -Hydrosaline retention and heart failure. 5. Recent studies: ADVANCE study: Combined treatment with an ACE inhibitor (perindropil) and a diuretic (indapamide) in fixed doses helps to reduce CV risk and overall mortality.DREAM study: Ramipril does not reduce the occurrence of DM2, but does improve reversion to normoglycemia. AVOID study: Direct renin inhibitors add greater antihypertensive and antiproteinuric efficacy. 6. New therapeutic targets: Antifibrotic, anti-inflammatory and antiproteinuric effects of sulodexide, isosorbide mononitrate, PKC inhibitors and others. 7. The most effective strategy continues to be intensive, multifactorial and multidisciplinary management of the type 2 diabetic patient, as shown by long-term follow-up in the Steno-2 study.
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PMID:[Advances in diabetes mellitus, diabetic nephropathy, metabolic syndrome and cardio-vascular-renal risk]. 1884 25