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 objective of this cross-sectional study was to investigate the relationship between factors of the coagulation- and fibrinolysis systems and insulin sensitivity in 104 clinically healthy, 58-years-old men. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, the metabolic syndrome according to a suggested definition, and different factors in the coagulation- and fibrinolysis system were determined. Subjects with the metabolic syndrome were characterised by increases in PAI-1 activity, tPA antigen, protein C and protein S and low concentrations of tPA activity. Insulin sensitivity was independently and reversibly associated with PAI-1 (p = 0.014) and directly with tPA activity (p = 0.001). Insulin sensitivity was also significantly negatively associated with protein S and protein C and several components in the metabolic syndrome, however not remaining significant in multivariate analyses. Protein C and protein S were significantly associated with PAI-1 activity, tPA activity (negatively), tPA antigen and antithrombin III. In conclusion, the data indicated that insulin resistance and several of the clustering components in the metabolic syndrome are accompanied by increased plasma concentrations of the anticoagulatory proteins C and S which may represent a mechanism which counteracts the concomitantly occurring hypofibrinolysis.
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PMID:Insulin sensitivity and hemostatic factors in clinically healthy 58-year-old men. 1105 52

The metabolic syndrome, in which insulin resistance is the core feature, is associated both with dysregulation of thrombosis/fibrinolysis and erythrocyte sodium/lithium countertransport (SLC). To investigate this further we designed a cross-sectional study to examine whether factors involved in coagulation- and fibrinolysis systems were associated with SLC independently of insulin resistance in 93 58-year-old men. SLC was in univariate analysis positively correlated with PAI-1 activity (r = 0.35, p <0.01), tPA antigen (r = 0.38, p <0.01), von Willebrand factor (r = 0.25, p <0.05), protein S (r = 0.26, p <0.05), and C (r = 0.30, p <0.01), and negatively associated with tPA activity(r = -0.28, p <0.01). Since these correlations could be influenced by the components of the metabolic syndrome itself, a separate analysis with adjustment for glucose infusion rate (GIR), plasma insulin, body fat, sagittal diameter of the abdomen (SD) and log serum triglyceride concentration (TG) was conducted. Then SLC was associated with tPA antigen independent of GIR, plasma insulin, body fat, SD and TG. SLC was also associated with protein C independent of GIR, insulin, body fat and SD but not TG. In conclusion, we found a relationship between SLC and the fibrinolytic system that was not related to the metabolic syndrome.
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PMID:Erythrocyte sodium/lithium countertransport is associated with thrombotic and fibrinolytic factors in 58-year-old men. 1517 2

There is a considerable body of evidence supporting an association between hypertriglyceridaemia, a hypercoagulable state and atherothrombosis. A disorder of triglyceride metabolism is a key feature of the metabolic syndrome that increases risk of both ischaemic heart disease and type 2 diabetes approximately 3-fold. An increasing prevalence of obesity and metabolic syndrome is likely to contribute markedly to the prevalent ischaemic heart in the foreseeable future, and therefore it is crucial to understand mechanisms linking hypertriglyceridaemia and a hypercoagulable state. Activation of platelets and the coagulation cascade are intertwined. VLDL and remnant lipoprotein concentrations are often increased with the metabolic syndrome. These lipoproteins have the capacity to activate platelets and the coagulation pathway, and to support the assembly of the prothrombinase complex. VLDL also upregulates expression of the plasminogen activator inhibitor-1 gene and plasminogen activator inhibitor-1 antigen and activity, a process accompanied by platelet aggregation and clot formation. The surface membrane of activated platelets also supports the assembly and activity of the prothrombinase complex, resulting in further thrombin generation and amplification of the coagulation cascade. Fibrinolysis is also less efficient when thrombin is generated. Thrombin induces thrombin activatable fibrinolysis inhibitor. Thrombin activatable fibrinolysis inhibitor is a carboxypeptidase that cleaves the carboxylic lysine residues on fibrin, thereby abolishing the critical binding site for tPA-plasminogen decreasing plasmin formation. Thus the evidence is supportive of dysregulated coagulation, and impaired fibrinolysis with a predisposition to atherothrombosis, in conditions such as the metabolic syndrome, in which there are increased concentrations of VLDL and remnant lipoproteins. The purpose of this review is to describe the current evidence supporting a procoagulant state induced by VLDL and remnant lipoproteins. The role of these lipoprotein classes in (1) platelet activation; (2) the intrinsic coagulation cascade, and (3) clot formation and fibrinolysis is discussed.
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PMID:Effects of VLDL and remnant particles on platelets. 1687 77

The aim of this study was to compare the effect of aliskiren and losartan on fibrinolysis and insulin sensitivity (IS) in hypertensive patients with metabolic syndrome. After 2-week placebo period, 76 outpatients with mild to moderate hypertension and metabolic syndrome were randomized to aliskiren 300 mg od or losartan 100 mg od for 12 weeks. Clinic blood pressure (BP), plasma PAI-1 antigen, and tPA activity were evaluated after 2, 4, 8, and 12 weeks of treatment. At the end of each treatment period patients performed an euglycemic hyperinsulinemic clamp and IS was assessed by glucose infusion rate (GIR). Both aliskiren and losartan induced a significant and similar SBP/DBP reduction (-15.6/10.7 mmHg and -15.5/10.5 mmHg, p<0.001 vs. baseline, respectively). Both drugs decreased PAI-1 antigen and activity after 2 weeks of treatment; subsequently, only the decreasing effect of aliskiren was sustained throughout the 12 weeks [-7.5 ng/ml (-31%) p<0.05 vs. baseline], while with losartan PAI-1 increased at week 12 [+3.6 ng/ml (+15%), p<0.05 vs. baseline and p<0.01 vs. aliskiren)]. The tPA activity showed no significant change with aliskiren and a decrease with losartan [-0.04 IU/ml (-8%), p<0.05 vs. baseline and p<0.01 vs. aliskiren]. Aliskiren significantly increased GIR [+1.4 mg/min/kg (+28%), p<0.01 vs. baseline] while losartan did not change it [+0.2 mg/min/kg (+4%), NS vs. baseline, p<0.05 vs. aliskiren)]. These results indicated that in this type of patients, despite similar BP reduction, aliskiren improved the fibrinolytic balance as well as IS, while losartan worsened the fibrinolytic balance and did not affect IS. The clinical relevance of these different effects remains to be clarified.
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PMID:Different effects of aliskiren and losartan on fibrinolysis and insulin sensitivity in hypertensive patients with metabolic syndrome. 2081 48