Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAl-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women: ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean t-PA antigen (5.15 +/- 3.02 vs 3.20 +/- 2.30 ng/ml) and PAl-1 antigen (35.89 +/- 18.59 vs 17.60 +/- 15.36 ng/ml) levels (p < 0.05). Plasma t-PA antigen level was not influenced by each treatment modality. There was a significant decrease of plasma PAl-1 antigen level after Metformin administration compared to that of before Metformin administration (39.74 +/- 19.39 vs 25.14 +/- 16.18 ng/ml) (p < 0.05), and the insulin-treated group showed a tendency for a decrease of plasma PAl-1 antigen levels after insulin administration but this did not reach statistical significance (29.93 +/- 15.37 vs 17.32 +/- 10.60 ng/ml). Sulfonylurea did not change both plasma t-PA and PAl-1 antigen levels. In conclusion, diabetic patients have high t-PA and PAl-1 antigen levels. Biguanide reduced plasma PAl-1 antigen levels, which might play some helpful role in the improvement of chronic complications in NIDDM.
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PMID:Plasma t-PA and PAl-1 antigen concentrations in non-insulin dependent diabetic patients: effects of treatment modality on fibrinolysis. 130 76

The hemovascular abnormalities encountered in diabetes include platelet alterations, shifts in prostaglandin metabolism and disorders of fibrinolysis. Diabetes is thus associated with increased platelet adhesiveness, increased platelet aggregation with hypersensitivity to proaggregants, increased plasma levels of beta-thromboglobulin and platelet factor 4 as an expression of platelet hyperactivity, increased levels of thromboxane A2 (TXA2) and prostacyclin (PGI2), and reduced levels of tissue plasminogen activator (t-PA). It is not clear which, if any, of these abnormalities are generated by chronic hyperglycemia and can be corrected by adequate glycemic control. Studies with gliclazide have demonstrated that it exerts hemovascular effects which can be valuable to patients. Thus, treatment with gliclazide leads to a decrease in platelet adhesiveness and aggregability. This treatment also reduces thromboxane levels and increases TPA levels. The mechanisms of action of gliclazide are not fully known but it has been demonstrated that its antiplatelet action is independent of its hypoglycemic activity and is not accompanied by clinical abnormalities of blood clotting. The mechanism of direct action on platelet activity may be mediated by inhibition of activated glycogen synthetase, activation of adenylate cyclase, modulation of arachidonic acid release from platelet membranes, stimulation of PGI2 production, and inhibition of the proaggregant action of TXA2. Thus, gliclazide not only has a hypoglycemic action but also improves hemovascular parameters in type 2 diabetes when used at normal therapeutic doses.
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PMID:Hemobiological activity of gliclazide in diabetes mellitus. 179 71

The pathogenesis of diabetic vasculopathy has been related to modifications in hemostasis and fibrinolysis. 50 non insulin dependent diabetes mellitus patients have been studied. Euglobulin clot lysis time, fibrin plate, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, Protein C and S, cholesterol, triglycerides and Hb A1c were determined in blood samples. Diabetic patients showed decreased fibrinolytic activity, as measured by ECLT, with clearly increased PAI levels. Fibrinolytic response to venous occlusion was lower than normal. Vascular complications were associated both with an even higher PAI activity and with a decreased fibrinolytic response to venous occlusion. Elevated PAI activity and decreased fibrinolytic response to stimulus may contribute to vascular disease in diabetes.
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PMID:Hypofibrinolysis associated with vasculopathy in non insulin dependent diabetes mellitus. 211 76

Parameters of fibrinolysis, including euglobulin fibrinolytic activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PA-inhibitor) activity, and plasmin-alpha 2-antiplasmin complex (PAP) were studied in 62 patients (35 women and 27 men; ages 53 +/- 16 years) with either insulin-dependent (IDDM) or noninsulin-dependent (NIDDM) diabetes mellitus. Compared to a control group of similar age (n = 57), the diabetic patients had a significantly lower mean euglobulin fibrinolytic activity (1.2 +/- 0.7 vs. 1.7 +/- 1.1 ng/ml, p less than 0.01) but significantly higher mean t-PA antigen (15.7 +/- 8.4 vs. 6.6 +/- 2.9 ng/ml, p less than 0.001) and PA-inhibitor activity (2.6 +/- 1.3 vs. 1.5 +/- 0.7 IU/ml, p less than 0.001) levels. Significant univariate correlations were observed between PA-inhibitor activity and age (r = 0.32, p less than 0.05), diastolic blood pressure (r = 0.42, p less than 0.01) and euglobulin fibrinolytic activity (r = -0.40, p less than 0.01). In multivariate analysis, only body mass index (positively) and euglobulin fibrinolytic activity (negatively) remained significantly related to PA-inhibitor activity in the total diabetic population as well as in the NIDDM group. The only parameter in the IDDM group significantly related to PA-inhibitor activity was diastolic blood pressure. These results suggest that PA-inhibitor plays a role in the regulation of fibrinolysis in diabetes patients and that factors like obesity and hypertension may be related to reduced fibrinolysis via PA-inhibitor levels.
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PMID:Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. 244 56

Four group of age- and sex-matched patients were studied: 1. nondiabetic subjects (n = 20) with a body mass index (BMI) < 25 Kg/m2 (lean control subjects); 2. obese non diabetic subjects (n = 22) with a BMI > 30 Kg/m2 (obese control subjects); 3. lean NIDDM subjects (n = 22); and 4. obese NIDDM subjects (n = 24). We determined: total cholesterol, triglycerides, HDL-cholesterol, blood glucose, Apolipoproteins A1 and B, insulin, Lp(a), Factor VII, fibrinogen, plasminogen, t-PA(Ag) pre and post venous occlusion (VO) and PAI activity pre and post VO. In addition to metabolic abnormalities obese non diabetic subjects and lean and obese NIDDM patients displayed significantly higher levels of fibrinogen, Factor VII, plasminogen, PAI pre and post VO and tPA(Ag) pre VO and significantly lower levels of t-PA(Ag) post VO. Our findings demonstrate an impairment of the haemostatic and fibrinolytic mechanisms which may be a key role in the pathogenesis of atherosclerotic vascular complications in obesity and in NIDDM.
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PMID:Blood coagulation and fibrinolysis in obese NIDDM patients. 764 83

The plasma levels of blood coagulation and fibrinolytic factors and the serum levels of lipids were measured in 62 subjects (22 normolipidemia and 40 hyperlipidemia) to investigate whether hyperlipidemia may affect the hemostatic system. Prothrombin, factors VII, IX and X were elevated in hyperlipidemic patients. The positive correlations were found between factors VII, IX and X, and triglyceride. The significant correlations were also found between VII and IX, and total cholesterol. Plasma levels of thrombin-antithrombin III complex (TAT), which reflects activation of coagulation system, were slightly but significantly higher in type IIb hyperlipidemia, although they were within normal range. Plasma levels of active plasminogen activator inhibitor (PAI) in type IIb and IV were significantly higher than in normals. A significant correlation was found between active PAI and triglyceride (r = 0.76, p < 0.0001). After the administration of fat emulsion to 18 patients with various diseases, which induced artificial hypertriglyceridemia, PAI levels as well as triglyceride levels significantly increased. These results suggest that hypertriglyceridemia may increase the synthesis and/or release of PAI, inducing a hypofibrinolytic condition, which could lead to thrombosis. It has been established that lipoprotein (a) [Lp(a)], which has a molecular structure homology to plasminogen, impairs fibrinolysis by its competitive inhibition of adsorption of plasminogen to vascular endothelial surface and/or fibrin. We assayed plasma levels of Lp(a) and parameters of blood coagulation and fibrinolysis in 168 patients with type II diabetes mellitus and 48 normal controls. In the diabetics, the levels of Lp(a) as well as levels of tissue-type plasminogen activator (t-PA) antigen and PAI activity were significantly higher than normal controls. Furthermore, it was shown that Lp(a) had a weakly negative correlation with t-PA antigen in the diabetics. These results suggest that an elevated level of Lp(a) may decrease release of t-PA, although the underlying mechanism remains unsolved.
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PMID:Hyperlipidemia and hemostatic system. 922 30

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Tumor necrosis factor-alpha (TNF-alpha) level, tissue-typed plasminogen activator(t-PA) activity and PA inhibitor (PAI) activity were determined in three groups: (1) 25 NIDDM patients with silent myocardial ischemia (SMI) or silent cerebral ischemia (SCI); (2) 18NIDDM patients without SMI or SCI; (3) 20 age-matched normal controls. Diagnosis of SMI or SCI was based on the finding of ischemic evidence by SPECT of myocardiotomograph or cerebrotomograph. All patients ECG and blood pressure were normal, and they had no history of clinical symptoms and signs of MI or CI. The result showed that the TNF-alpha level and PAI activity in the ischemia group were the highest and the t-PA activity in the ischemia group was the lowest, as compared with those in the other two groups respectively. It suggests that in NIDDM patients who have high TNF-alpha, high PAI activity, low t-PA, and even no symptoms and signs of MI or CI, anticoagulant therapy might be useful to prevent the progression of diabetic macroangiopathies.
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PMID:[Changes of serum TNF-alpha level, t-PA activivty and PAI activity in patients with silent myocardial ischemia or silent cerebral ischemia]. 1068 70

The fundamental role of insulin resistance for metabolic changes linked to cardiovascular disease and type 2 diabetes is increasingly recognized. Oral contraceptives (OC) may affect insulin sensitivity, and a detailed characterization hereof, as well as the secondary effects on related metabolic systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We conclude that the treatments were followed by a compensated decrease in insulin sensitivity that was unrelated to changes in triglycerides, t-PA, or PAI-1 antigen.
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PMID:Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives. 1071 68

Troglitazone, a novel oral insulin sensitizer, normalizes increased plasma activity of plasminogen activator inhibitor type 1 (PAI-1) in hyperinsulinemic patients such as women with polycystic ovary syndrome and patients with type 2 diabetes mellitus. However, underlying mechanisms have not yet been fully elucidated. Human hepatic and vascular cells, the main sources of circulating PAI-1, were studied in cell culture. In human hepatic cells, PAI-1 accumulated in conditioned medium by 23% within 24 h after exposure to 3 microg/mL troglitazone (P = 0.001). The accumulation depended on the concentration of troglitazone, but not that of insulin (known to stimulate PAI-1 synthesis). By contrast, in human aortic smooth muscle cells, 3 microg/mL troglitazone decreased basal PAI-1 expression by 23% (P = 0.037) and decreased transforming growth factor-beta-induced expression by 34% (P = 0.026). Concomitant insulin had no effect. Tissue-type plasminogen activator was decreased by 38% (P = 0.002). In human endothelial cells, PAI-1 was diminished by 32% (P < 0.001), whereas tissue-type plasminogen activator was unaffected. The results suggest that the reduction in plasma activity of PAI-1 induced by troglitazone in patients may reflect both directly mediated diminution of its elaboration from vessel walls and indirectly mediated reduction of its hepatic synthesis secondary to attenuation of hyperinsulinemia (known to increase the hepatic synthesis of PAI-1).
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PMID:Differential regulation by troglitazone of plasminogen activator inhibitor type 1 in human hepatic and vascular cells. 1077 Jan 98


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