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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty acid metabolism is abnormal in insulin-resistant states that increase the risk of atherosclerosis such as type 2 diabetes and the metabolic syndrome. How fatty acids promote vascular disease is poorly understood, but lipoprotein lipase and peroxisome proliferator-activated receptor alpha (PPARalpha)-physiologically related proteins involved in fatty acid metabolism-may be involved. Glucocorticoid metabolism is also abnormal in insulin-resistant states and may promote several components of the metabolic syndrome. Recent studies have shown that hepatic fatty acid metabolism is required for the development of insulin resistance and hypertension caused by glucocorticoid excess, suggesting that crosstalk between glucocorticoid receptor-and PPARalpha-dependent pathways may contribute to vascular disease.
Trends Cardiovasc Med 2004 Feb
PMID:Fatty acid metabolism and vascular disease. 1503 Jul 93

Endothelial dysfunction is a feature of a variety of clinical states of insulin resistance, and increasingly it is recognized that pre-diabetic states of insulin resistance are associated not only with insulin resistance but with increased cardiovascular risk. The metabolic syndrome which typically accompanies insulin resistance brings aberrations in a number of classical cardiovascular risk factors, but it appears that insulin resistance itself represents an additional, non-classical risk factor. Therefore, the approach to treating the endothelium in patients with the metabolic syndrome might include therapies targeting insulin resistance. In this review, we provide a detailed overview of the current state of knowledge regarding the biguanide metformin and its effects on the endothelium. Its mode of action is reviewed, along with the available data from laboratory and experimental studies related to vascular function in animals and in humans. Metformin has beneficial effects on endothelial function which appear to be mediated through its effects to improve insulin resistance. Therapeutically targeting insulin resistance appears to be a viable route to improving endothelial function in clinical states of insulin resistance.
Curr Drug Targets Cardiovasc Haematol Disord 2004 Mar
PMID:Insulin resistance as a therapeutic target for improved endothelial function: metformin. 1503 52

We recently established that the Dahl salt-sensitive rat, a model for genetic salt-sensitive hypertension, was insulin resistant. This study was undertaken to evaluate whether other features of the metabolic syndrome developed in this animal model. Two groups of 16 Dahl salt-sensitive (DSS) rats and their controls, Dahl salt-resistant (DSR) rats were used. For eight weeks, half of each group was fed a standard diet with low sodium content (85 mmol Na/kg diet) while the remainder was fed a high-sodium diet (340 mmol Na/kg diet). Weekly systolic and diastolic blood pressures were measured for all animals. At the end of eight weeks, the urinary Na(+)/K(+) ratio, fasting blood glucose, plasma uric acid and blood lipids were determined for all animals. The same parameters were measured in two additional matched weanling DSS and DSR groups of eight animals each. Adult DSS rats became hypertensive, with the DSS high-salt group exhibiting both genetic hypertension and the pressor effects of a high-salt diet. The DSS high-salt and weanling groups exhibited a lowered urinary Na(+)/K(+) ratio, indicative of greater sodium retention, when compared to their respective DSR groups (p < 0.05). No strain differences were observed in the uric acid levels. However a high-salt diet in both DSS and DSR groups elevated uric acid levels. Weanling and DSS high-salt groups showed increased total plasma cholesterol when compared to their corresponding DSR groups (p < 0.05). In addition, the DSS high-salt group also had both increased total plasma cholesterol and high-density lipoprotein (HDL) cholesterol when compared to the DSS low-salt group (p < 0.05). No significant differences in blood glucose and plasma insulin were observed in the adult groups. The weanling DSS group showed a marked hyperinsulinaemia, suggesting that DSS rats were possibly insulin resistant even before hypertension was fully established. This could indicate that insulin resistance and hypertension may be inherited as separate traits that develop in a parallel but independent manner.
Cardiovasc J S Afr
PMID:Facets of the metabolic syndrome in Dahl hypertensive rats. 1514 36

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.
Expert Rev Cardiovasc Ther 2004 Mar
PMID:Treatment of metabolic syndrome. 1515 70

The metabolic syndrome (MetS) is a common multiplex cluster of phenotypes strongly related to cardiovascular disease that includes central obesity with hypertension, dyslipidemia, and type 2 diabetes. The core molecular defect of the MetS is insulin resistance; indeed, the terms "MetS" and "insulin resistance syndrome" often are used interchangeably. The successful translation to clinical medicine of molecular genetic research on other rare monogenic metabolic disorders has stimulated the evaluation of such rare monogenic forms of insulin resistance as partial lipodystrophy resulting from mutations in either LMNA or PPARG genes. Careful phenotypic evaluation of carriers of monogenic insulin resistance using a range of diagnostic methods--an approach sometimes called "phenomics"--may help to find early presymptomatic biomarkers of cardiovascular disease, which, in turn, may uncover new pathways and targets for interventions for the common MetS, diabetes, and atherosclerosis.
Trends Cardiovasc Med 2004 May
PMID:Phenomics, lipodystrophy, and the metabolic syndrome. 1517 63

Many clinical studies have demonstrated that lipid-altering drug treatments, including the use of statin and niacin monotherapy, can be effective in the primary and secondary prevention of coronary heart disease, but only in a minority of patients relative to placebo. Since statins and niacin have entirely different mechanisms of action and predominantly different effects on blood lipid levels, the combined use of both a statin and niacin may confer complementary benefits on multiple lipid parameters, produce a more global improvement in lipid blood levels and result in greater reductions in coronary heart disease risk factors than the administration of either agent alone. This may be of particular importance in patients with complex dyslipidemias, such as those with Type 2 diabetes mellitus and metabolic syndrome. This review summarizes the efficacy and safety of extended-release niacin/lovastatin (Advicor, Kos Pharmaceuticals Inc.), the first combination product approved for the management of dyslipidemia.
Expert Rev Cardiovasc Ther 2004 Jul
PMID:Extended-release niacin/lovastatin: the first combination product for dyslipidemia. 1522 9

Potentially important new findings have recently been reported concerning the so-called metabolic syndrome in relation to the renin-angiotensin system, ie, that treatment with inhibitors of the angiotensin-converting enzyme (ACE) not only decreases blood pressure levels but prevents the development of diabetes mellitus. The new findings described in this article highlight the potential role of the ACE system in the regulation of insulin sensitivity, thus contributing to the development of type 2 diabetes and metabolic syndrome. In addition to the well known selective effects of ACE inhibitors and angiotensin II receptor blockers in reducing microalbuminuria in diabetic patients, the potential ability of these drugs to reduce the risk of diabetes and the metabolic syndrome would support their use as first line agents not only in diabetic patients but also in selected groups of hypertensive patients, who are particularly at risk of developing metabolic complications. This information supports the Joint Guidelines for the Management of Arterial Hypertension by the European Society of Hypertension and the European Society of Cardiology, which highlight the crucial role of ACE inhibitors and the angiotensin II receptor blockers in preventing the development of diabetes in hypertensive patients.
Nutr Metab Cardiovasc Dis 2004 Apr
PMID:The role of the renin angiotensin hormonal system in the metabolic syndrome and type 2 diabetes. 1524 41

Visceral obesity is frequently associated with high plasma triglycerides and low plasma high density lipoprotein-cholesterol (HDL-C), and with high plasma concentrations of apolipoprotein B (apoB)-containing lipoproteins. Atherogenic dyslipidemia in these patients may be caused by a combination of overproduction of very low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance. Weight reduction, increased physical activity, and moderate alcohol intake are first-line therapies to improve lipid abnormalities in visceral obesity. These lifestyle changes can effectively reduce plasma triglycerides and low density lipoprotein-cholesterol (LDL-C), and raise HDL-C. Kinetic studies show that in visceral obesity, weight loss reduces VLDL-apoB secretion and reciprocally upregulates LDL-apoB catabolism, probably owing to reduced visceral fat mass, enhanced insulin sensitivity and decreased hepatic lipogenesis. Adjunctive pharmacologic treatments, such as HMG-CoA reductase inhibitors, fibric acid derivatives, niacin (nicotinic acid), or fish oils, may often be required to further correct the dyslipidemia. Therapeutic improvements in lipid and lipoprotein profiles in visceral obesity can be achieved by several mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. Clinical trials have provided evidence supporting the use of HMG-CoA reductase inhibitors and fibric acid derivatives to treat dyslipidemia in patients with visceral obesity, insulin resistance and type 2 diabetes mellitus. Since drug monotherapy may not adequately optimize dyslipoproteinemia, dual pharmacotherapy may be required, such as HMG-CoA reductase inhibitor/fibric acid derivative, HMG-CoA reductase inhibitor/niacin and HMG-CoA reductase inhibitor/fish oils combinations. Newer therapies, such as cholesterol absorption inhibitors, cholesteryl ester transfer protein antagonists and insulin sensitizers, could also be employed alone or in combination with other agents to optimize treatment. The basis for a multiple approach to correcting dyslipoproteinemia in visceral obesity and the metabolic syndrome relies on understanding the mechanisms of action of the individual therapeutic components.
Am J Cardiovasc Drugs 2004
PMID:Dyslipidemia in visceral obesity: mechanisms, implications, and therapy. 1528 98

The metabolic syndrome and type 2 diabetes mellitus are increasingly associated with cardiovascular disease morbidity and mortality in African Americans. African Americans are specifically prone to the negative effects of hypertension and risk factor clustering associated with the metabolic syndrome and diabetes. Data demonstrate a decrease in cardiovascular events in diabetic patients with secondary prevention and, most recently, primary prevention with lipid-lowering therapy. African Americans should benefit from intense risk factor control, including antihypertensive therapy and lipid lowering, to prevent cardiovascular disease. Appropriate lifestyle modification programs, glucose control, and cardiovascular risk reduction therapy will reduce the excessive morbidity and mortality in this population.
Rev Cardiovasc Med 2004
PMID:The epidemic of diabetes mellitus and the metabolic syndrome in African Americans. 1530 83

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.
Am J Cardiovasc Drugs 2004
PMID:Significance of high density lipoprotein-cholesterol in cardiovascular risk prevention: recommendations of the HDL Forum. 1544 72


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