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

Coronary heart disease (CHD) is a common, costly, and undertreated disorder in the United States, and dyslipidemia is one of its most important modifiable risk factors. Recently, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) published updated guidelines for the treatment of lipid disorders, greatly expanding the number of patients eligible for therapy. In the new recommendations, several significant changes have been made in the identification and management of patients at risk for CHD. Although ATP III maintains that low-density lipoprotein (LDL) cholesterol should be the primary target of lipid-lowering therapy, it identifies non-high-density lipoprotein (HDL) cholesterol (total cholesterol minus HDL cholesterol) as a secondary target in patients with elevated triglycerides. Patients with > or = 2 CHD risk factors should now be assessed for 10-year absolute CHD risk based on the Framingham Point Scale to identify those who require more aggressive treatment. The guidelines also designate a new category, CHD risk equivalent, which recognizes that certain patients have the same high risk as those with established CHD. Diabetes is now identified as a CHD risk equivalent, as are other forms of atherosclerotic disease and multiple risk factors comprising a CHD 10-year risk of > 20%. New lipoprotein classifications are given, and increased emphasis is placed on the metabolic syndrome, a constellation of metabolic risk factors, as a marker for CHD risk. Since adherence poses a major challenge in the management of patients with or at risk for CHD, the new guidelines provide physicians with several strategies for increasing patient compliance. The new guidelines should help physicians better identify and manage patients at risk for CHD, help more patients reach their lipid goals, and thereby decrease cardiovascular morbidity and mortality.
Am J Manag Care 2002 Sep
PMID:New therapeutic options in the National Cholesterol Education Program Adult Treatment Panel III. 1224 Jul 1

Coronary heart disease is a leading cause of death in industrialized nations. Hyperlipidemia with elevated serum total cholesterol, LDL cholesterol, and triglycerides is a known major cardiovascular risk factor. HDL cholesterol is considered to be protective, so low HDL cholesterol is being recognized as an independent cardiovascular risk factor that contributes to the development of atherosclerosis and related adverse cardiovascular events. The recognition of insulin resistance and metabolic syndrome is a step further in understanding these risk factors. Attempts at reducing serum cholesterol with different strategies in the past have met with limited success until the development of statins. The advent of statins has revolutionized the management of hyperlipidemia. The post-statins era has seen major clinical trials demonstrating the benefit of cholesterol reduction in the setting of both primary and secondary prevention. In general, there appears to be a 25% to 40% relative risk reduction in major adverse cardiovascular events such as death, myocardial infarction, and stroke. The recent megatrials further suggest that aggressive management of cholesterol in patients with high cardiovascular risk may be beneficial. Though the concept of the-lower-the-better may be looming, the question of "How low is good enough?" remains controversial. The results of recent megatrials such as the Heart Protection Study go a step further than the NCEP guidelines and suggest that statin therapy may benefit patients at high risk of cardiovascular disease regardless of their baseline values. We summarize the results of the available large clinical trials in our understanding of the management of dyslipidemia in a setting of primary prevention.
Curr Opin Cardiol 2002 Sep
PMID:Management of dyslipidemia in the primary prevention of coronary heart disease. 1235 27

Metabolic syndrome, insulin resistance, prediabetes, and overt type 2 diabetes mellitus are associated with an accelerated atherosclerosis (atheroscleropathy). This quartet is also associated with multiple metabolic toxicities resulting in the production of reactive oxygen species. The redox stress associated with these reactive oxygen species contribute to the development, progression, and the final fate of the arterial vessel wall in prediabetic and diabetic atheroscleropathy. The prevention of morbidity and mortality of these intersecting metabolic diseases can be approached through comprehensive global risk reduction.
Cardiovasc Diabetol 2002 Sep 27
PMID:Intimal redox stress: accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy. 1239

The aim of the present study was to investigate the association between the serum lipid profile and components of the metabolic syndrome, such as central obesity (anthropometric, computed tomography and fat cell data), insulin, sex-hormone-binding-globulin (SHBG) and different hormones influencing this important syndrome, e.g. sex steroids, leptin and tumor necrosis factor-alpha (TNF-alpha). The sample consisted of 85 obese patients (30 men and 55 women) who had undergone abdominal surgery. Fasting serum lipids were analysed, as well as anthropometric and computed tomography data, perivisceral and subcutaneous fat cell size and serum glucose and hormones. Abdominal fat revealed itself as an important correlator of the adverse changes in plasma lipoprotein levels, the waist-to-hip-ratio and waist-to-thigh-ratio being the best morphological correlators in men and women, respectively. Intra-abdominal fat (VA) correlated significantly and positively to perivisceral fat cell size in women, while no correlation was found between subcutaneous fat accumulation (SA) and adipocyte size in both genders. Perivisceral fat cell size showed the greatest number of correlations with the adverse plasma lipid profile compared to that in the subcutaneous depot. SHBG and sex steroids showed a negative correlation with serum lipids considered a cardiovascular risk. In contrast, TNF-alpha and C-peptide were inversely correlated with potential protector lipids. In conclusion, abdominal obesity, adipocyte hypertrophy from visceral fat, serum TNF-alpha and C-peptide seem to be the best correlators of the lipoprotein disturbance characteristic of the metabolic syndrome, whereas SHBG and sex steroids could play a protective role regarding the lipid profile associated to this syndrome.
J Physiol Biochem 2002 Sep
PMID:Interrelationship between serum lipid profile, serum hormones and other components of the metabolic syndrome. 1260 9

Inhibition of acetyl-CoA carboxylase (ACC), with its resultant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation, has the potential to favorably affect the multitude of cardiovascular risk factors associated with the metabolic syndrome. To achieve maximal effectiveness, an ACC inhibitor should inhibit both the lipogenic tissue isozyme (ACC1) and the oxidative tissue isozyme (ACC2). Herein, we describe the biochemical and acute physiological properties of CP-610431, an isozyme-nonselective ACC inhibitor identified through high throughput inhibition screening, and CP-640186, an analog with improved metabolic stability. CP-610431 inhibited ACC1 and ACC2 with IC50s of approximately 50 nm. Inhibition was reversible, uncompetitive with respect to ATP, and non-competitive with respect to bicarbonate, acetyl-CoA, and citrate, indicating interaction with the enzymatic carboxyl transfer reaction. CP-610431 also inhibited fatty acid synthesis, triglyceride (TG) synthesis, TG secretion, and apolipoprotein B secretion in HepG2 cells (ACC1) with EC50s of 1.6, 1.8, 3.0, and 5.7 microm, without affecting either cholesterol synthesis or apolipoprotein CIII secretion. CP-640186, also inhibited both isozymes with IC50sof approximately 55 nm but was 2-3 times more potent than CP-610431 in inhibiting HepG2 cell fatty acid and TG synthesis. CP-640186 also stimulated fatty acid oxidation in C2C12 cells (ACC2) and in rat epitrochlearis muscle strips with EC50s of 57 nm and 1.3 microm. In rats, CP-640186 lowered hepatic, soleus muscle, quadriceps muscle, and cardiac muscle malonyl-CoA with ED50s of 55, 6, 15, and 8 mg/kg. Consequently, CP-640186 inhibited fatty acid synthesis in rats, CD1 mice, and ob/ob mice with ED50s of 13, 11, and 4 mg/kg, and stimulated rat whole body fatty acid oxidation with an ED50 of approximately 30 mg/kg. Taken together, These observations indicate that isozyme-nonselective ACC inhibition has the potential to favorably affect risk factors associated with the metabolic syndrome.
J Biol Chem 2003 Sep 26
PMID:Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis, and increase fatty acid oxidation in cultured cells and in experimental animals. 1284 71

Oxidative stress may play a role in the pathophysiology of diabetes and cardiovascular disease, but little is known about antioxidant status among individuals with the metabolic syndrome who are at high risk for developing these conditions. Using data from the Third National Health and Nutrition Examination Survey (1988-1994), we compared circulating concentrations of vitamins A, C, and E; retinyl esters; five carotenoids; and selenium in 8,808 U.S. adults aged > or = 20 years with and without the metabolic syndrome. After adjusting for age, sex, race or ethnicity, education, smoking status, cotinine concentration, physical activity, fruit and vegetable intake, and vitamin or mineral use, participants with the metabolic syndrome had significantly lower concentrations of retinyl esters, vitamin C, and carotenoids, except lycopene. With additional adjustment for serum lipid concentrations, vitamin E concentrations were significantly lower in participants with the metabolic syndrome than those without the syndrome. Retinol concentrations were similar between the two groups. After excluding participants with diabetes, the results were very similar. Consumption of fruits and vegetables was also lower among people with the metabolic syndrome. Adults with the metabolic syndrome have suboptimal concentrations of several antioxidants, which may partially explain their increased risk for diabetes and cardiovascular disease.
Diabetes 2003 Sep
PMID:The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. 1294 75

Dr Winkelmann is the Head of the Cooperation Unit for Pharmacogenomics and Applied Genomics in Heidelberg, which was founded in 2001 by the Department of Internal Medicine VI and the Coordination Centre for Clinical Trials at the University of Heidelberg. His main interests are sophisticated phenotyping procedures for patient characterization and the conduct of multicenter clinical trials according to international standards with state-of-the-art data management. He currently applies new genomic tools in order to achieve progress in personalized medicine using collaborating networks of general practitioners for patient enrollment. The focus of his research group is on the common complex genetic cardiovascular and metabolic diseases ranging from coronary artery disease, dyslipidemia and hypertension, to metabolic syndrome and diabetes mellitus. In collaboration with partners from biotech, the genomic techniques used in clinical studies include haplotyping of candidate genes, gene expression profiling of peripheral leucocytes and proteomics in order to identify new biomarkers of effect in therapeutic studies or pathway/target gene identification in disease-specific family studies using microarray-based linkage approaches. An innovative web-based remote data entry system with an integrated pedigree drawing tool is used in the family studies. Dr Winkelmann is also involved as the clinical database coordinator for a European Framework VI research initiative of leading European centers in cardiovascular genetics for identification of risk genes for atherothrombosis in coronary artery disease by transcriptome and proteome analysis and high throughput exon resequencing at the Wellcome Trust Sanger Institute, Cambridge, UK.
Pharmacogenomics 2003 Sep
PMID:Pharmacogenomics, genetic testing and ethnic variability: tackling the ethical questions. 1294 62

As the incidence of Type 2 diabetes has reached near epidemic proportions, the quest for novel therapies to combat this disorder has intensified dramatically. In recent years, the peroxisome proliferator-activated receptor (PPAR) family has received tremendous attention as perhaps an ideal target class to address the multiple metabolic anomalies associated with the diabetic state. This review focuses on a variety of novel PPAR approaches currently being investigated for Type 2 diabetes or the metabolic syndrome, including the highly potent selective PPAR agonists, PPAR combination agonists and alternative PPAR ligands.
Expert Opin Investig Drugs 2003 Sep
PMID:Novel peroxisome proliferator-activated receptor ligands for Type 2 diabetes and the metabolic syndrome. 1294 93

Two isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert the active glucocorticoid, cortisol, and inactive cortisone. 11beta-HSD1 acts predominantly as an oxo-reductase in vivo using NADP(H) as a cofactor to generate cortisol. In contrast, 11beta-HSD2 is a NAD-dependent dehydrogenase inactivating cortisol to cortisone, thereby protecting the mineralocorticoid receptor from occupation by cortisol. In peripheral tIssues, both enzymes serve to control the availability of cortisol to bind to corticosteroid receptors. 11beta-HSD2 protects the mineralocorticoid receptor from cortisol excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of 'apparent mineralocorticoid excess', in which 'Cushing's disease of the kidney' results in cortisol-mediated mineralocorticoid excess. Inhibition of 11beta-HSD2 explains the mineralocorticoid excess state seen following liquorice ingestion and more subtle defects in enzyme expression might be involved in the pathogenesis of 'essential' hypertension. 11beta-HSD1 by generating cortisol in an autocrine fashion facilitates glucocorticoid receptor-mediated action in key peripheral tIssues including liver, adipose tissue, bone and the eye. 'Cushing's disease of the omentum' has been proposed as an underlying mechanism in the pathogenesis of central obesity and raises the exciting possibility of selective 11beta-HSD1 inhibition as a novel therapy for patients with the metabolic syndrome. 'Pre-receptor' metabolism of cortisol via 11beta-HSD isozymes is an important facet of corticosteroid hormone action. Aberrant expression of these isozymes is involved in the pathogenesis of diverse human diseases including hypertension, insulin resistance and obesity. Modulation of enzyme activity may offer a future therapeutic approach to treating these diseases whilst circumventing the endocrine consequences of glucocorticoid excess or deficiency.
Eur J Endocrinol 2003 Sep
PMID:Tissue-specific Cushing's syndrome, 11beta-hydroxysteroid dehydrogenases and the redefinition of corticosteroid hormone action. 1294 16

We hypothesized that the association of high sensitivity C-reactive protein (CRP) with urinary albumin excretion (UAE) is predominately mediated through its correlation with the metabolic syndrome. Serum CRP and urine albumin:creatinine ratios (ACR) from 720 preventive cardiology patients were analyzed to estimate age- and gender-adjusted relative risk of high CRP and metabolic syndrome for high ACR. These data demonstrate that CRP independently predicts the presence of UAE, a marker of endothelial dysfunction.
Am J Cardiol 2003 Sep 01
PMID:Relation of albumin/creatinine ratio to C-reactive protein and to the metabolic syndrome. 1294 89


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