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

The metabolic syndrome is a constellation of metabolic risk factors for atherosclerotic cardiovascular disease (ASCVD) occurring in one individual. There are five cardiovascular risk factors that accompany the metabolic syndrome: atherogenic dyslipidemia [elevated apolipoprotein B (apo B), elevated triglyceride, small low-density lipoprotein (LDL) particles, and low high-density lipoprotein (HDL)cholesterol], elevated blood pressure, elevated glucose, a prothrombotic state, and a proinflammatory state. The likelihood of an individual developing metabolic syndrome is enhance by underlying risk factors, notably, obesity, insulin resistance, lack of physical activity, advancing age, and hormonal factors (e.g., androgens and corticosteroids). Besides being at higher risk for ASCVD, persons with the metabolic syndrome are at increased risk for type 2 diabetes. Persons with the metabolic syndrome deserve management in the clinical setting to reduce the risk for both ASCVD and type 2 diabetes. The two major therapeutic strategies for treatment of affected persons are modification of the underlying risk factors and separate drug treatment of the particular metabolic risk factors when appropriate. First-line therapy for underlying risk factors is therapeutic lifestyle changes, i.e., weight loss in obese persons, increased physical activity, and anti-atherogenic diet. These changes will improve all of the metabolic risk factors. Whether use of drugs to reduce insulin resistance is effective, safe, and cost-effective before the onset of diabetes awaits the results of more clinical research. Turning to individual risk components, for atherogenic dyslipidemia, drug therapies that promote lowering of apo B and raise HDL cholesterol will be needed for higher risk patients. Treatment of categorical hypertension with drugs has become standard practice. When hyperglycemia reaches the diabetic level, glucose-lowering agents will become necessary when dietary control is no longer effective, and reduction of a prothrombotic state with low-dose aspirin may be indicated in higher-risk patients.
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PMID:Metabolic syndrome: therapeutic considerations. 1659 97

Available evidence clearly indicates a rapid progression in the prevalence of obesity worldwide. As a consequence, there has also been a marked increase in the prevalence of type 2 diabetes all over the world and this chronic metabolic disease is now considered as a coronary heart disease risk equivalent. However, even in the absence of the hyperglycaemic state which characterizes type 2 diabetic patients, non diabetic individuals with a specific form of obesity, named abdominal obesity, often show clustering metabolic abnormalities which include high triglyceride levels, increased apolipoprotein B, small dense low dendity lipoproteins and decreased high density lipoproteins-cholesterol levels, a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as well as an inflammatory profile. This agglomeration of abnormalities has been referred to as the metabolic syndrome which can be identified by the presence of three of the five following variables: abdominal obesity, elevated triglyceride concentrations, low HDL-cholesterol levels, increased blood pressure and elevated fasting glucose. Post-mortem analyses of coronary arteries have indicated that obesity (associated with a high accumulation of abdominal fat measured at autopsy) was predictive of earlier and greater extent of large vessels atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome linked to abdominal obesity is also predictive of recurrent coronary events both in post-myocardial infarction patients and among coronary artery disease men who underwent a revascularization procedures. It is suggested that until the epidemic progression of obesity is stopped and obesity prevented or at least properly managed, cardiologists will be confronted to an evolving contribution of risk factors where smoking, hypercholesterolemia and hypertension may be relatively less prevalent but at the expense of a much greater contribution of abdominal obesity and related features of the metabolic syndrome.
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PMID:[Impact of obesity in contemporary cardiology]. 1659 98

The childhood obesity epidemic has begun to compromise the health of the pediatric population by promoting premature development of atherosclerosis and the metabolic syndrome (MS), both of which significantly increase the risk of cardiovascular disease (CVD) early in life. As a result, recently, there has been increased recognition of the need to assess and closely monitor children and adolescents for risk factors of CVD and components of the MS. Serum/Plasma biomarkers including total cholesterol, triglycerides, HDL-C, LDL-C, insulin and C-peptide have been used for this purpose for many years. Recently, emerging biomarkers such as apolipoprotein AI, apolipoprotein B, leptin, adiponectin, free fatty acids, and ghrelin have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers, if not more powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender, pubertal stage, and ethnic origin are a necessity. Unfortunately, to date, many critical gaps exist in the reference interval database of most of the biomarkers that have been identified. This review contains a comprehensive gap analysis of the reference intervals for emerging and traditional risk biomarkers of CVD and the MS and discusses the clinical significance and analytical considerations of each biomarker.
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PMID:Gap analysis of pediatric reference intervals for risk biomarkers of cardiovascular disease and the metabolic syndrome. 1662 72

The aim of the present study was to investigate the association between changes in apoB (apolipoprotein B-100) kinetics and plasma PLTP (phospholipid transfer protein) and CETP (cholesteryl ester transfer protein) activities in men with MetS (the metabolic syndrome) treated with fenofibrate. Eleven men with MetS underwent a double-blind cross-over treatment with fenofibrate (200 mg/day) or placebo for 5 weeks. Compared with placebo, fenofibrate significantly increased the FCRs (fractional catabolic rates) of apoB in VLDL (very-low-density lipoprotein), IDL (intermediate-density lipoprotein) and LDL (low-density lipoprotein) (all P<0.01), with no significant reduction (-8%; P=0.131) in VLDL-apoB PR (production rate), but an almost significant increase (+15%, P=0.061) in LDL-apoB PR. Fenofibrate significantly lowered plasma TG [triacylglycerol (triglyceride); P<0.001], the VLDL-TG/apoB ratio (P=0.003) and CETP activity (P=0.004), but increased plasma HDL (high-density lipoprotein)-cholesterol concentration (P<0.001) and PLTP activity (P=0.03). The increase in PLTP activity was positively associated with the increase in both LDL-apoB FCR (r=0.641, P=0.034) and PR (r=0.625, P=0.040), and this was independent of the fall in plasma CETP activity and lathosterol level. The decrease in CETP activity was positively associated with the decrease in VLDL-apoB PR (r=0.615, P=0.044), but this association was not robust and not independent of changes in PLTP activity and lathosterol levels. Hence, in MetS, the effects of fenofibrate on plasma lipid transfer protein activities, especially PLTP activity, may partially explain the associated changes in apoB kinetics.
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PMID:Relationships between changes in plasma lipid transfer proteins and apolipoprotein B-100 kinetics during fenofibrate treatment in the metabolic syndrome. 1676 53

Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production, conversion, or catabolism of lipoprotein particles. Studies in hypolipoproteinemia and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. Here, we review the current knowledge regarding apolipoprotein B (apoB) metabolism, focusing on selected clinically relevant conditions. In hypobetalipoproteinemia attributable to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome, it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL-apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB, and mutant forms of proprotein convertase subtilisin/kexin type 9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.
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PMID:Thematic review series: patient-oriented research. What we have learned about VLDL and LDL metabolism from human kinetics studies. 1672 Aug 94

The microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipoprotein B-containing lipoproteins. Emerging evidence has indicated that the functional MTP exon polymorphism I128T is associated with dyslipidemia and other traits of the insulin-resistance syndrome, and the T128 variant seems to confer a reduced stability of MTP, resulting in reduced binding of LDL particles. The aim of the study was to elucidate the association of this MTP polymorphism with parameters of postprandial metabolism. A total of 716 male subjects from a postprandially characterized cohort (MICK) and a nested case-control study (EPIC) of 190 incident type 2 diabetes cases and 380 sex- or age-matched controls were genotyped for the I128T exon polymorphism. In comparison to homozygote subjects of the wild allele, carriers of the less common allele of the MTP T128 genotype showed significantly lower postprandial insulin levels (P=0.017), lower diastolic blood pressure (P=0.049) and had a lower prevalence of impaired glucose metabolism and diabetes type 2 (P=0.03) in the MICK. Consistent with this, we found a lower incidence of type 2 diabetes in male subjects of the nested case-control study in the T128 genotype (P=0.007). These results suggest that the rare allele of the MTP I128T polymorphism may be protective against impaired glucose tolerance, type 2 diabetes and other parameters of the metabolic syndrome.
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PMID:A common functional exon polymorphism in the microsomal triglyceride transfer protein gene is associated with type 2 diabetes, impaired glucose metabolism and insulin levels. 1672 86

Atherogenic dyslipidemia, a component of metabolic syndrome, is characterized by high levels of apolipoprotein B (apo B)-containing lipoproteins, including very-low-density lipoprotein remnants and small low-density lipoprotein particles, and reduced levels of high-density lipoprotein cholesterol. Although the National Cholesterol Education Program Adult Treatment Panel III includes elevations in blood pressure and plasma glucose in the definition of metabolic syndrome, the broader scope of metabolic syndrome includes proinflammatory and prothrombotic states, which derive from the secretory activity of adipose tissue. Abdominal fat can adversely affect insulin action and the disposal of glucose through an increase in the release of free fatty acid, resulting in accumulation of triglyceride in muscle and liver, thereby depressing insulin action and increasing output of apo B-containing lipoproteins. Impaired regulation of adipokines, bioactive substances secreted from adipose tissue, likely produces systemic inflammation, which can promote atherogenesis. Insulin resistance is recognized as an important metabolic defect linking the components of metabolic syndrome. One molecule that may play an important role in metabolic syndrome to regulate metabolic and vascular pathways is the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Studies have established PPAR-gamma deficiency as a cause of lipodystrophy and confirmed its adipogenic role. Patients with atherogenic dyslipidemia and metabolic syndrome should undergo global risk assessment for cardiovascular disease and future cardiovascular events to determine an overall treatment strategy.
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PMID:Atherogenic dyslipidemia associated with metabolic syndrome and insulin resistance. 1690 66

Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B)--emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP - Bezafibrate Infarction Prevention study, HHS - Helsinki Heart Study, VAHIT--Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD--Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy--selected on the basis of their safety and effectiveness - may offer particularly desirable benefits in patients with combined hyperlipidemia as compared with statins monotherapy.
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PMID:Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins. 1700 98

Recently, small dense low-density lipoprotein (sd-LDL) has been highlighted as a new risk factor for CHD. Sd-LDL is also closely associated with insulin resistance and hypertriglyceridemia, suggesting a high prevalence of these atherogenic particles in metabolic syndrome. It has been proposed that increased triglyceride (TG) production in the liver due to insulin resistance preferentially produces TG-rich very-low density lipoproteins (VLDL1), which finally generate sd-LDL particles. Sd-LDL is usually measured by electrophoresis or ultracentrifugation, but these methods are too laborious for general clinical use. Recently, we established a simple method for the quantification of sd-LDL-cholesterol (C) using heparin-magnesium precipitation with a filter, which selectively detects cholesterol in the denser LDL fraction with a density(d) =1.044-1.063g/ml. Patients with coronary heart disease (CHD) had substantially increased sd LDL-C levels, while their LDL-C levels were comparable to those of controls. Sd-LDL-C levels were positively correlated with TG, LDL C, and apolipoprotein B, and were inversely with HDL-C. Sd-LDL-C levels were also correlated positively with waist circumference, blood pressure, and insulin resistance index, and negatively with adiponectin level. Patients with type 2 diabetes and metabolic syndrome had substantially increased sd-LDL-C level. These results suggest that measurement of sdLDL-C is useful to evaluate overall atherogenic risks associated with metabolic syndrome and may be applicable to routine clinical examination.
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PMID:[Metabolic syndrome and small dense LDL-cholesterol]. 1759 88

Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy. However, all lipoproteins containing apolipoprotein B (apo B) appear to be atherogenic. Preferred targets of therapy therefore may include either the cholesterol in all apo B-containing lipoproteins (non-high-density lipoprotein cholesterol [non-HDL-C]) or total apo B itself. Apo B can be measured by three methods: chemically, by nuclear magnetic resonance (NMR), and by immunoassay. This study compares the first two methods as a function of the number of metabolic risk factors in patients with metabolic syndrome. Plasma lipid, lipoprotein cholesterol, and apo B levels were measured in 274 adults with varying numbers of metabolic syndrome components. Low-density lipoprotein (LDL) particle sizes were measured by gel electrophoresis and by NMR. Total apo B was estimated chemically and by conversion of NMR lipoprotein particle number, assuming one apo B molecule per lipoprotein particle. As the number of metabolic syndrome components increased, apo B rose by both chemical and NMR methods, but by chemical methods, increases were in the triglyceride-rich fraction, whereas by NMR, they were in LDL. The correlation between total apo B measured by the two methods was only moderate (r = .73). Further, non-HDL-C was more highly correlated with total apo B measured chemically than either LDL-C or total apo B by NMR. Non-HDL-C correlates highly with total apo B in patients with metabolic syndrome and had advantages as a target of therapy over LDL-C or NMR apo B.
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PMID:Relationship of apolipoprotein B levels to the number of risk factors for metabolic syndrome. 1785 Jul 35


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