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)

Cardiovascular risk factors were compared between 126 people with non-insulin-dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random sample of people (Chinese, Malays, and Asian Indians) aged 40-69 years from the general population of Singapore. Data were adjusted for age and ethnicity. For both genders, people with NIDDM had higher mean body mass indices, waist-hip ratios and abdominal diameters. They also had a higher prevalence of hypertension, higher mean levels of fasting serum triglyceride, slightly lower mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator (antigen). These factors are components of syndrome X (metabolic syndrome) and increase the risk of atherosclerosis and thrombosis. In contrast, there were no important differences for cigarette smoking, serum total and low-density-lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and plasma prothrombin fragment 1 + 2. Females with NIDDM, but not males, had a higher mean serum fibrinogen level than non-diabetics, which could explain why NIDDM has a greater cardiovascular effect in females than males. Serum lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls, but there were no important differences for plasma vitamins A, C and E, and serum selenium, which are anti-oxidants.
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PMID:Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore. 954 28

While there is indisputable evidence supporting the beneficial role of aerobic exercise in reducing cardiovascular risk factors, there are few dose-response studies of this relationship. Increasingly, it is thought that the cardiovascular benefits of exercise are significantly influenced by adaptations within skeletal muscle and its vasculature. However, little is known about the molecular mechanisms underlying these adaptations. To address this need, we initiated a study utilizing longitudinal, microarray-based gene expression profiling of serial skeletal muscle biopsies obtained from the study of targeted risk reduction intervention through defined exercise (STRRIDE). STRRIDE participants were overweight and exhibited symptoms characteristic of the metabolic syndrome that typically precedes type II diabetes such as insulin resistance, abnormal lipids and glucose intolerance. Expression data were statistically filtered and sorted into exercise training-responsive clusters based on gene product knowledge. One such cluster included genes that promote the degradation of fibrin clots such as tissue plasminogen activator (t-PA), connective tissue activation peptide III (CTAP III) and tetranectin. The fibrinolytic activity and protein levels of tetranectin, and t-PA and its endogenous inhibitor PAI-1, were subsequently shown to change significantly in both skeletal muscle and serum in response to exercise training. Our data show that the rigors of exercise directly induce fibrinolytic genes and protein cascades, both within muscle, and in the systemic circulation. This finding is particularly significant given that the metabolic syndrome is an independent risk factor for peripheral vascular disease and thrombotic events within the heart and brain. We conclude that aerobic exercise training induces both local and systemic changes in fibrinolysis and vascular homeostasis that are probably protective against cardiovascular disease.
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PMID:Skeletal muscle dictates the fibrinolytic state after exercise training in overweight men with characteristics of metabolic syndrome. 1261 18

Elevated levels of haemostatic factors including tissue plasminogen activator (t-PA) antigen are associated with coronary heart disease in Europeans but data in South Asians are sparse. We performed a cross-sectional study of 111 healthy men and women aged 40-55 years (56 European and 55 Asian) frequency matched across a wide range of body mass index (17-34 kg/m2). All subjects had detailed adiposity and metabolic measurements, and five haemostatic factors were determined. South Asians had greater insulin resistance than Europeans (fasting insulin geometric mean, 7.1 versus 4.7 microU/ml, and 2-h insulin, 37.3 versus 14.1 microU/ml, respectively). There were no significant ethnic differences in the mean concentrations of fibrinogen, factor VII, von Willebrand factor, or fibrin D-dimer (P > 0.10). However, the t-PA antigen concentration was significantly elevated in South Asians compared with Europeans (mean, 10.6 versus 8.2 ng/ml, P = 0.001). t-PA correlated positively in both ethnic groups with features of the metabolic syndrome but the ethnic difference in t-PA persisted after adjustment for adiposity, metabolic and inflammatory variables (beta = 2.0, 95% confidence interval = 0.5-3.6, P = 0.012). We therefore hypothesize that elevated t-PA antigen may be a novel mechanism contributing to increased cardiovascular risk in South Asians.
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PMID:Specific elevation in plasma tissue plasminogen activator antigen concentrations in South Asians relative to Europeans. 1461 56

Obesity is the central promoter of the metabolic syndrome which also includes disturbed fibrinolysis in addition to hypertension, dyslipidaemia and impaired glucose tolerance/type 2 diabetes mellitus. Plasminogen activator inhibitor-1 (PAI-1) is the most important endogenous inhibitor of tissue plasminogen activator and uro-plasminogen activator, and is a main determinant of fibrinolytic activity. There is now compelling evidence that obesity and, in particular, an abdominal type of body fat distribution are associated with elevated PAI-1 antigen and activity levels. Recent studies established that PAI-1 is expressed in adipose tissue. The greater the fat cell size and the adipose tissue mass, the greater is the contribution of adipose production to circulating PAI-1. Experimental data show that visceral adipose tissue has a higher capacity to produce PAI-1 than subcutaneous adipose tissue. Studies in human adipocytes indicate that PAI-1 synthesis is upregulated by insulin, glucocorticoids, angiotensin II, some fatty acids and, most potently, by cytokines such as tumour necrosis factor-alpha and transforming growth factor-beta, whereas catecholamines reduce PAI-1 production. Interestingly, pharmacological agents such as thiazolidinediones, metformin and AT(1)-receptor antagonists were found to reduce adipose expression of PAI-1. In addition, weight loss by dietary restriction or comprehensive lifestyle modification is effective in lowering PAI-1 plasma levels. In conclusion, impaired fibrinolysis in obesity is probably also due to an increased expression of PAI-1 in adipose tissue. An altered function of the endocrine system and an impaired auto-/paracrine function at the fat cell levels may mediate this disturbance of the fibrinolytic system and thereby increase the risk for cardiovascular disease..
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PMID:Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. 1535 68

The metabolic syndrome is characterized by a combination of obesity, chronic inflammation and insulin resistance. This syndrome also has features of a hypercoagulable state, consisting of increased levels of clotting factors (tissue factor, factor VII and fibrinogen) as well as inhibition of the fibrinolytic pathway (increased plasminogen activator inhibitor-1 and decreased tissue plasminogen activator activity). Simultaneously, the presence of endothelial dysfunction and dyslipidemia triggers platelet aggregability, thus further increasing the risk of thrombotic events both in the arterial and venous system. Although mechanisms of coagulation activation are well described for other diseases, the precise etiology is not well known in the metabolic syndrome. Thus far, only obesity has been shown to be a modest risk factor for venous thromboembolic events, whereas accurate data for metabolic syndrome patients are lacking. Hence, routine interventions for prevention of venous thromboembolism are not yet warranted. However, as dyslipidemia is associated with procoagulant changes, this could be a possible target for therapeutic intervention. In view of the rising incidence of metabolic syndrome even at a young age, both the incidence of venous thromboembolism and the effect of intervention on markers of hypercoagulability in metabolic syndrome call for further studies.
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PMID:Hypercoagulability in the metabolic syndrome. 1578 Aug 24

We investigated the effect of a high walnut and cashew diet on haemostatic variables in people with the metabolic syndrome. Factor analysis was used to determine how the haemostatic variables cluster with other components of the metabolic syndrome and multiple regression to determine possible predictors. This randomized, control, parallel, controlled-feeding trial included 68 subjects who complied with the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a 3-week run-in following the control diet, subjects were divided into three groups receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks. The nut intervention had no significant effect on von Willebrand factor antigen, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1 activity, tissue plasminogen activator activity or thrombin activatable fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass-correlates and acute phase response factors, and factor VII coagulant activity clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen activator activity, plasminogen activator inhibitor 1 activity and von Willebrand factor antigen clustered into a separate endothelial function factor. HDL-C and markers of obesity were the strongest predictors of the haemostatic variables. We conclude that high walnut and cashew diets did not influence haemostatic factors in this group of metabolic syndrome subjects. The HDL-C increase and weight loss may be the main focus of dietary intervention for the metabolic syndrome. Furthermore, diet composition may have only limited effects if weight loss is not achieved.
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PMID:Clustering of haemostatic variables and the effect of high cashew and walnut diets on these variables in metabolic syndrome patients. 1609 34

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide and was responsible for 7.2 million deaths in 2003. Various studies have pointed out that South Asians have a higher prevalence of CAD as compared with other ethnicities. South Asians may have a genetic predisposition to CAD; however, environmental, nutritional, and lifestyle factors may also be responsible. South Asians have a much higher prevalence of metabolic syndrome, diabetes, insulin resistance (and resultant hyperinsulinemia), central obesity, dyslipidemias (lower high-density lipoprotein, increased lipoprotein[a], higher triglyceride levels), increased thrombotic tendency (increased plasminogen activator inhibitor-1 and decreased tissue plasminogen activator levels), decreased levels of physical activity, and low birth weights ("fetal origins hypothesis"). In addition, the dietary indiscretions and sedentary lifestyle practiced by most South Asians puts them at a higher risk. A multidisciplinary approach involving the population at risk, healthcare personnel, and the government is required to diminish the incidence. Educational programs regarding the genetic predisposition as well as risk factors for CAD, physical activity, and dietary modifications need to be encouraged. There is a need for implementation of newer guidelines as well as a lower threshold for initiating therapeutic interventions in this population. Mass media should be involved to bring about behavioral changes, and these changes should be reinforced at the physician's level.
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PMID:Coronary artery disease in South Asians: an emerging risk group. 1649 44

Females with a history of premature adrenarche are at high risk of developing polycystic ovary syndrome (PCOS) and features of the metabolic syndrome later in life. Coagulation disorders, subclinical inflammation, and oxidative stress have been reported in patients with PCOS and metabolic syndrome. These factors were studied in a group of adolescents with a history of premature adrenarche. This is a cross-sectional study that determined the biochemical-hormonal profile and indices of inflammation, coagulation, and oxidative stress in 45 adolescent girls with a history of premature adrenarche and 19 age- and body mass index-matched controls. Girls with premature adrenarche had hyperandrogenism and higher indices of insulin resistance than controls. They also had significantly higher C-reactive protein (0.76 +/- 0.65 vs 0.41 +/- 0.31 mg/L, P = .0001) and plasminogen activator inhibitor 1 (37.6 +/- 24.7 vs 24.47 +/- 4.6 ng/mL, P = .034), and lower tissue plasminogen activator values in comparison with controls (3.5 +/- 1.5 vs 5.2 +/- 2.12 ng/mL, P = .0019). Both C-reactive protein(r = 0.545, P = .0001) and plasminogen activator inhibitor 1 (r = 0.36, P = .04) were positively correlated with oxidative stress, whereas tissue plasminogen activator was positively correlated (r = 0.37, P = .02) with total antioxidant status. None of these factors was correlated with androgens or indices of insulin resistance. Adolescent girls with a history of premature adrenarche display metabolic deviations usually encountered in subjects with PCOS and metabolic syndrome, such as subclinical inflammation and fibrinolytic abnormalities.
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PMID:Elevated coagulation and inflammatory markers in adolescents with a history of premature adrenarche. 1930 81

In this review we discuss the association of overall hypofibrinolysis and individual fibrinolytic protein levels with venous and arterial thrombosis. Decreased overall fibrinolytic potential and high plasma levels of thrombin-activatable fibrinolysis inhibitor have been consistently associated with risk of venous thrombosis, whereas little evidence exists for a role of plasminogen, alpha2-antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor 1. Overall fibrinolytic potential has been associated with arterial thrombosis in young individuals, but studies on the individual components gave conflicting results. These inconsistent results could be a consequence of nonfibrinolytic properties of fibrinolytic proteins, including roles in inflammation, vascular remodeling, atherosclerosis, and the metabolic syndrome. The nonfibrinolytic properties of these proteins may have opposing effects on development of arterial disease as compared with the lytic properties, which may explain opposite results in different studies with slightly different population characteristics. These properties may be more relevant in arterial than in venous thrombosis.
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PMID:The impact of the fibrinolytic system on the risk of venous and arterial thrombosis. 1973 37

Individuals with metabolic syndrome (MetS) often have elevated plasma plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA), contributing to an increased risk of cardiovascular disease. PAI-1 and t-PA may be affected by chronic (n-3) long-chain PUFA [(n-3)LCPUFA] supplementation; however, the acute impact of fat ingestion on these risk factors has not been established. Our objective was to investigate the acute effect of (n-3)LCPUFA on plasma PAI-1, t-PA, and platelet aggregation. We conducted a randomized crossover study in which men (n = 8, > or =45 y) with MetS consumed water or a high-saturated fat beverage (1 g fat/kg body weight) with either a high or low content of (n-3)LCPUFA. Blood samples were collected over 8 h to measure triacylglycerol (TAG), PAI-1, t-PA, and platelet aggregation. Both fat loads resulted in a significant increase in whole blood TAG concentration, plasma PAI-1 and t-PA concentrations, and PAI-1 activity, as well as a significant decrease in t-PA activity during the postprandial period. Interestingly, PAI-1 concentration and activity increased more following the high (n-3)LCPUFA compared with the low (n-3)LCPUFA beverage (P < 0.05). Furthermore, the high (n-3)LCPUFA beverage resulted in a lower t-PA activity (P < 0.05), whereas the effects of the 2 fat loads on the plasma t-PA concentration and platelet aggregation did not differ. Overall, acute intake of a high (n-3)LCPUFA beverage shifted the balance between plasma PAI-1 and t-PA, which might indicate a lower capacity for fibrinolysis.
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PMID:Acute ingestion of long-chain (n-3) polyunsaturated fatty acids decreases fibrinolysis in men with metabolic syndrome. 1988 9


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