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 diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were stablished in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established. Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, metglitinides and thiazolidinediones, to prevent both T2DM and cardiovascular events. In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.
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PMID:Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis, clinical implications and management. 1630 67

The metabolic syndrome is characterized by the clustering of insulin resistance, dyslipidemia, and hypertension and is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. However, older antihypertensive agents such as thiazide diuretics and beta-blockers have potentially adverse effects on glucose and lipid metabolism and may even the exacerbate the metabolic syndrome and increase risk of type 2 diabetes. Recent clinical trials have suggested that antihypertensive agents that inhibit the renin-angiotensin system may reduce risk for new-onset type 2 diabetes, but only a few of these studies were placebo controlled, and in most cases, the absolute antidiabetic effects were relatively modest. Evidence is accumulating that telmisartan, in addition to blocking the angiotensin II type 1 receptor, activates the peroxisome proliferator-activated receptor (PPAR)-gamma a well-known target for treatment of the metabolic syndrome and diabetes. By contrast, other angiotensin-receptor blockers are largely devoid of activity on PPAR-gamma. Telmisartan is a partial agonist of PPAR-gamma and has a superior tolerability profile without causing the fluid retention and edema associated with full agonists of PPAR-gamma such as pioglitazone and rosiglitazone. Recent studies have indicated that in addition to antidiabetic properties, PPAR-gamma activators may also provide protection against atherosclerosis and coronary events. Thus, the ability of telmisartan both to activate PPAR-gamma and to block the angiotensin receptor may provide added value not only in the treatment of the metabolic syndrome and prevention of type 2 diabetes but also in prevention and treatment of atherosclerotic cardiovascular disease.
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PMID:New treatment strategies for patients with hypertension and insulin resistance. 1656 44

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

Cardiovascular disease is the leading cause of death in Type 2 diabetes, which commonly occurs in patients with serious mental illnesses (SMIs). We determined the extent to which patients with diabetes and SMI, relative to diabetes patients without SMI, met American Diabetes Association goals for cholesterol and blood pressure, met criteria for the metabolic syndrome, and were prescribed medications known to reduce cardiovascular events. We found that less than half of diabetes patients, both with and without SMI, met recommended goals for cholesterol levels; even fewer had adequate blood pressure control. In addition, a substantial proportion of all diabetes patients met metabolic syndrome criteria. However, diabetes patients with SMI were less likely to be prescribed cholesterol-lowering statin medications, angiotensin-converting enzyme inhibitors, and angiotensin receptor blocking agents than diabetes patients without SMI. Patients with both diabetes and SMI are treated less aggressively for high cardiovascular risk than diabetes patients without mental disorders.
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PMID:Extent and management of cardiovascular risk factors in patients with type 2 diabetes and serious mental illness. 1677 56

Hypertension is a cardiovascular risk factor commonly associated with insulin resistance, the metabolic syndrome, and type 2 diabetes mellitus. Recent in vitro data indicate that certain angiotensin receptor antagonists, for example, telmisartan, activate peroxisome proliferator-activated receptor gamma (PPAR-gamma) and increase adiponectin protein content in adipocytes. By this means, they may improve insulin sensitivity in vivo. To investigate the effect of antihypertensive treatment on insulin sensitivity and fasting adiponectin serum levels, 37 nondiabetic patients with essential hypertension were randomized to receive telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks in a prospective, parallel group study. Fasting serum glucose, insulin, and adiponectin were evaluated before, 3 weeks (low dose), and 6 weeks (high dose) after initiation of treatment. Furthermore, the effect of telmisartan on PPAR-gamma receptor activity was investigated in vitro using a PPAR-gamma reporter gene assay. As reported previously, telmisartan significantly enhanced PPAR-gamma receptor activity in vitro. At baseline, a positive correlation between insulin serum levels and body mass index of investigated subjects was observed, whereas body mass index and serum adiponectin levels were negatively associated. High-dose treatment with telmisartan but not with nisoldipine reduced serum insulin levels as well as the homeostasis model assessment of insulin resistance, but did not affect serum adiponectin levels. In conclusion, in our study cohort of nondiabetic patients with essential hypertension, telmisartan improved insulin sensitivity by mechanisms apparently not involving adiponectin induction. Future studies will demonstrate whether these telmisartan-induced effects may contribute to a blood pressure-independent reduction in cardiovascular morbidity.
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PMID:Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension. 1691 33

It is well recognised that the metabolic syndrome, a constellation of risk factors including obesity, hypertension, insulin resistance and dyslipidaemia, is associated with an increased risk of cardiovascular complications and the development of Type 2 diabetes. Consequently, timely identification and management of all components of the metabolic syndrome is warranted. In particular, guidelines have emphasised the importance of targeting elevated blood pressure (BP) and dyslipidaemia as a method of reducing global cardiovascular risk. Findings from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial show that the angiotensin receptor blocker, valsartan, reduces cardiovascular events and the development of Type 2 diabetes in high-risk individuals. This profile is being further explored in the ongoing Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Given the potential advantages to patients and physicians of tackling more than one of the components of the metabolic syndrome, antihypertensive agents such as valsartan would appear to be and important addition to the management of vulnerable patients at high risk of cardiovascular events.
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PMID:Angiotensin receptor blockers: Cardiovascular protection in the metabolic syndrome. 1698 30

Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 +/- 2.7 versus 2.9 +/- 2.2 muU/ml x mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-alpha, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 +/- 16 versus 92 +/- 14 mg/dl; P < 0.05), insulin (23.1 +/- 8.8 versus 19.9 +/- 9; P < 0.05), HOMA index (6.0 +/- 2.7 versus 4.7 +/- 2.8; P < 0.05), and glycated hemoglobin (5.33 +/- 0.58 versus 4.85 +/- 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 +/- 100 versus 370 +/- 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy.
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PMID:Insulin resistance, inflammatory biomarkers, and adipokines in patients with chronic kidney disease: effects of angiotensin II blockade. 1713 Feb 63

The current pandemic of diabetes mellitus will inevitably be followed by an epidemic of chronic kidney disease. It is anticipated that 25-40% of patients with type 1 diabetes and 5-40% of patients with type 2 diabetes will ultimately develop diabetic kidney disease. The control of blood pressure represents a key component for the prevention and management of diabetic nephropathy. There is a strong epidemiological connection between hypertension in diabetes and adverse outcomes in diabetes. Hypertension is closely linked to insulin resistance as part of the 'metabolic syndrome'. Diabetic nephropathy may lead to hypertension through direct actions on renal sodium handling, vascular compliance and vasomotor function. Recent clinical trials also support the utility of blood pressure reduction in the prevention of diabetic kidney disease. In patients with normoalbuminuria, transition to microalbuminuria can be prevented by blood pressure reduction. This action appears to be significant regardless of whether patients have elevated blood pressure or not. The efficacy of ACE inhibition appears to be greater than that achieved by other agents with a similar degree of blood pressure reduction; although large observational studies suggest the risk of microalbuminuria may be reduced by blood pressure reduction, regardless of modality. In patients with established microalbuminuria, ACE inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) consistently reduce the risk of progression from microalbuminuria to macroalbuminuria, over and above their antihypertensive actions. The clinical utility of combining these strategies remains to be established. In patients with overt nephropathy, blood pressure reduction is associated with reduced urinary albumin excretion and, subsequently, a reduced risk of renal impairment or end stage renal disease. In addition to actions on systemic blood pressure, it is now clear that ACE inhibitors and ARBs also reduce proteinuria in patients with diabetes. This anti-proteinuric activity is distinct from other antihypertensive agents and diuretics. Although there is a clear physiological rationale for blockade of the renin angiotensin system, which is strongly supported by clinical studies, to achieve the optimal lowering of blood pressure, particularly in the setting of established diabetic renal disease, a number of different antihypertensive agents will always be needed. In the end, the choice of agents should be individualised to achieve the maximal tolerated reduction in blood pressure and albuminuria. Ultimately, no matter how it is achieved, so long as it is achieved, renal risk can be reduced by agents that lower blood pressure and albuminuria.
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PMID:Blood pressure lowering for the prevention and treatment of diabetic kidney disease. 1713 4

Metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for the development of cardiovascular disease and type 2 diabetes. Together with obesity and dyslipidaemia, hypertension is one of the basic elements of the metabolic syndrome. Current guidelines do not provide specific recommendation for pharmacological management of the hypertensive patients with metabolic syndrome. Recent trials have consistently shown that therapy involving beta-blockers and diuretics may have some negative impact on metabolic and haemodynamic disorders present in metabolic syndrome. Several lines of evidence support the use of angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers as the appropriate first-line therapy and calcium channel blockers, as the second, in the patients with metabolic syndrome.
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PMID:[Metabolic syndrome in patients with hypertension]. 1721 93

Arterial hypertension is frequently associated with type 2 diabetes mellitus, and both of these diseases are the major risk factors for cardiovascular complications. During the past few years, a number of large randomized clinical trials examined the frequency of new onset diabetes mellitus during administration of antihypertensive drugs. Application of ACE inhibitors or angiotensin receptor blockers reduces the risk for the onset of diabetes mellitus by 20-27%, and calcium channel blockers by 16%. Despite some uncertainties, novel studies have demonstrated an increased risk for cardiovascular complications related to new onset diabetes mellitus. The duration of patient monitoring is also an important factor, as the onset of diabetes-related complications is closely associated with the duration of this disease. Considering all above, the aim of preventing the onset of diabetes is to recognize patients with an increased risk. The risk factors include basal glycemia, positive family history for diabetes mellitus, obesity, metabolic syndrome, and some ethnic groups (South Asia, the Caribbeans). Therefore, increased-risk patients should be subjected to therapy with ACE inhibitor, angiotensin receptor blocker, or calcium channel blocker as the first drug of choice. For these patients, application of thiazides and beta blockers or the combination of these two drugs is not advantageous. However, such a view poses a dilemma whether thiazide diuretics should be the first choice in the treatment of hypertension.
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PMID:[Antihypertensive agents and the risk of new onset diabetes mellitus]. 1721 94


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