Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various hemostatic abnormalities have been reported and excess activation of coagulation factors, such as prothrombin, factor VII, factor IX, and factor XI, have been detected in thrombotic diseases states by various assay systems. We recently developed the enzyme-linked differential immunoassay for activated factor XI-alpha 1 antitrypsin complex (FXIa-alpha 1 AT) and applied it with other assays for activated factors such as thrombin-antithrombin III complex (TAT) to detect the hypercoagulable state in clinical samples. In patients with DIC, the FXIa-alpha 1 AT level in plasma increased before onset of DIC. In patients with non-insulin-dependent diabetes mellitus, FXIa-alpha 1AT and TAT levels were increased in the patient plasma. FXIa-alpha 1AT was related to the severity of urinary albumin excretion, whereas TAT was not. Plasma FXIa-alpha 1AT levels were significantly increased in patients with angiographically proven coronary artery disease, and showed a positive correlation with TAT, fibrinogen, and Lp(a). Evaluation of activated coagulation factor provides useful information on the diagnosis of thrombotic disease.
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PMID:[Activated coagulation factors in various thrombotic diseases]. 856 28

The contact activation of intrinsic pathway in the coagulation system accompanied by plasma kallikrein-induced kinin generation is thought to be involved in the pathogenesis of diabetic retinopathy. Plasma prekallikrein (PPK), a proenzyme of plasma kallikrein, is a single-chain glycoprotein synthesized mainly in the liver. The aim of our study was to evaluate plasma prekallikrein level in diabetic patients and to examine the relationship between PPK and the metabolic control of diabetes and development of retinopathy. In 53 diabetic patients and 33 healthy subjects as controls the following parameters have been assessed: plasma prekallikrein, serum fructosamine, glycated haemoglobin HbA1c, prothrombin time, partial thromboplastin time and antithrombin III (AT III). Compared to the control group, PPK level was significantly higher in diabetics, especially in patients with proliferative retinopathy. The significant positive correlations have been found between PPK and HbA1c in diabetic patients and between PPK and serum fructosamine concentration but only in diabetics without retinopathy. No differences in prothrombin time and AT III have been observed between diabetics and healthy subjects. A suggestion is presented on increase of plasma prekallikrein level in diabetics due to hyperglycaemia-stimulated glycoprotein over-synthesis in the liver, what would confirm the role of kallikrein-kinin system in the pathogenesis of microangiopathy.
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PMID:[Elevated plasma prekallikrein level in patients with diabetes]. 859 45

It has been previously demonstrated that hyperglycaemia activates haemostasis; diabetes mellitus is considered a thrombosis-prone state. Acarbose, by inhibiting dietary carbohydrate absorption, reduces post-meal hyperglycaemia. In this study we evaluated the effect of post-meal hyperglycaemia on two markers of coagulation activation: prothrombin fragments 1 + 2 and D-dimer. Seventeen non-insulin-dependent diabetic patients maintained on diet therapy alone were randomly assigned to receive- with a cross-over study design-acarbose (100 mg orally) or placebo before a standard meal. Blood samples for measurement of plasma glucose, insulin, prothrombin fragments 1 + 2 and D-dimer were drawn at 0, 60, 120 and 240 min. After both placebo and acarbose, hyperglycaemia and hyperinsulinaemia which followed a standard meal were accompanied by a significant increase of plasma concentration of prothrombin fragments 1 + 2 and D-dimer in comparison to their baseline values. Acarbose administration significantly reduced the rise of glucose, insulin, prothrombin fragments 1 + 2 and D-dimer from 0 to 240 min in comparison to placebo. We conclude that post-meal hyperglycaemia, at the level reached by many diabetic patients on diet therapy alone, induces a coagulation activation. Acarbose, by decreasing post-meal hyperglycaemia, may be useful in reducing meal-induced activation of haemostasis in diabetic patients.
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PMID:Post-meal coagulation activation in diabetes mellitus: the effect of acarbose. 877 97

Studies suggest that thrombosis is important in the progression of atherosclerotic lesions. The biochemical markers prothrombin fragment 1-2 and fibrinopeptide A reflect in vivo thrombin generation and activity, respectively. As such, they are markers that might be associated with cardiovascular risk. From the Cardiovascular Health Study, a cohort study of 5201 persons over 65 years of age, 399 persons free of clinical cardiovascular disease (CVD) at the baseline examination were selected for study of specialized markers of hemostasis. We report the cross-sectional relationships of the thrombin markers to CVD risk factors and measures of subclinical CVD. The range of fragment 1-2 2 was 0.12 to 0.85 nmol/L. The range of fibrinopeptide A was 0.9 to 44.1 micrograms/L. High levels of fragment 1-2 and fibrinopeptide A were associated with age, with levels higher in women than men. Fragment 1-2 was associated with smoking; high levels of triglyceride, creatinine, and C-reactive protein; and low levels of glucose. Fibrinopeptide A was associated with high C-reactive protein and apolipoprotein(a) and lower ankle-brachial index. There were no significant associations of the thrombin markers with race, fibrinogen, alcohol consumption, diabetes, or most measures of subclinical CVD. Study findings support a hypothesis that there are physiological interrelationships between cardiac risk factors, hemostasis, inflammation, and progression of atherosclerosis.
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PMID:Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease. 879 70

To evaluate whether or not activated coagulation is present in the preclinical phases of type 2 diabetes mellitus, we studied 46 non-diabetic first-degree relatives of type 2 diabetic patients and 21 matched controls with no family history of diabetes. We determined the plasma levels of prothrombin fragment 1 + 2, D-dimer, fibrinogen, plasminogen activator inhibitor type 1, tissue plasminogen activator, von Willebrand factor and coagulation factors VII and VIII. Glucose tolerance, beta-cell function and insulin sensitivity were assessed in all subjects by a continuous glucose infusion of 5 mg.kg ideal body weight-1.min-1 for 60 min with model assessment of glucose, insulin and C-peptide values. Plasma levels of prothrombin fragment 1 + 2 (median 1.24 vs 0.68 nmol.l-1; P = 0.0001) and D-dimer (331 vs 254 micrograms.l-1 UEF; P = 0.018) were higher in relatives, without significant differences in the other haemostatic variables. Relatives showed higher fasting (5.5 vs 4.9 mmol.l-1, P = 0.004) and post-infusion (9.3 vs 8.3 mmol.l-1, P = 0.02) serum glucose, no differences in insulin or C-peptide levels, lower beta-cell function (122% vs 147%; P = 0.02) and no significant differences in insulin sensitivity. Fifteen relatives were glucose-intolerant and had lower beta-cell function and insulin sensitivity than glucose-tolerant relatives. Both subsets of relatives exhibited higher levels of prothrombin fragment 1 + 2 and D-dimer than control subjects. Thus, first-degree relatives of type 2 diabetic patients present an activated coagulation, even in the absence of minor degrees of glucose intolerance. These abnormalities can play a role in the pathogenesis of cardiovascular diseases frequently seen at diagnosis of type 2 diabetes.
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PMID:Increased prothrombin fragment 1 + 2 and D-dimer in first-degree relatives of type 2 diabetic patients. Prethrombotic state in relatives of type 2 diabetic patients. 887 Aug 13

Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble E-selectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 +/- 3.8 vs 3.0 +/- 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 +/- 2.6 vs 35.3 +/- 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 +/- 0.6 vs 8.6 +/- 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 +/- 2.9 vs 23.4 +/- 2.6%, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin.
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PMID:Protein C activation in NIDDM patients. 896 Aug 26

Atrial fibrillation is an independent risk factor for cerebral and systemic embolism. The risk increases with the patient's age and the presence of other risk factors: hypertension, diabetes, cardiac failure, prior transient ischemic attacks or embolic stroke. Risk stratification is of essential importance to allow the choice of the most suitable prophylaxis with antithrombotic drugs for the individual patient. On the basis of the results of controlled clinical trials, it is possible to suggest the following guidelines: a) in patients at low risk (< 65 years, with no other risk factor) the drug of first choice should be acetylsalicylic acid; b) in patients at high risk (> 65 years, with one or more risk factors) the drugs of first choice are oral anticoagulants, given at doses that prolong the prothrombin time to INR values of 2-3; c) in patients at high risk with contraindications to oral anticoagulants, acetylsalicylic acid or indobufen (shown to be as effective as oral anticoagulants in patients with prior transient ischemic attacks or stroke) should be considered.
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PMID:[Prevention of thromboembolism in atrial fibrillation of non-valvular etiology]. 900 15

Type 1 (insulin-dependent) diabetes mellitus is associated with long-term vascular complications. In addition to metabolic factors, immunological and haemostatic mechanisms may be involved. Lupus anticoagulant (LA), an immunoglobulin which interferes with endothelial cell function, is frequently associated with a high risk of thromboembolic events. LA has been described in several diseases but never in diabetes mellitus. The aim of this study was to evaluate if endothelial dysfunction and unmodulated haemostasis are amplified by the presence of LA in Type 1 diabetic patients. Plasma samples collected from clinically and biochemically well-characterized Type 1 diabetic patients were examined for LA, fibrinogen, prothrombin (PT), PTT, prothrombin degradation products (F1 + 2) and activated protein C (APC). The results revealed significantly decreased APC and increased F1 + 2 plasma concentrations in LA-positive but not in LA-negative patients; 60% of LA-positive and only 18% of LA-negative patients had microangiopathy (not significant). No thrombotic episodes in large vessels were found in LA-positive patients. These findings suggest that LA could be considered an additional factor in the onset and/or progression of diabetic complications, acting as a link between the immunological and haemostatic systems in the pathogenesis of diabetic microangiopathy.
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PMID:Diabetic microangiopathy: lupus anticoagulant dependent thrombotic tendency in type 1 (insulin-dependent) diabetes mellitus. 904 90

Recently, we found an increase in tissue factor pathway inhibitor (TFPI) activity in patients with insulin-dependent diabetes mellitus (IDDM). This increase in TFPI activity could be the result of increased thrombin formation and/or altered binding of TFPI to glycosaminoglycans. We studied TFPI activity (chromogenic assay) in relation to prothrombin F1 + 2 fragments and endogenous thrombin potential (ETP), in 46 IDDM patients, and 18 age and sex-matched healthy controls. Prothrombin, antithrombin and thrombomodulin were also determined. In IDDM patients, TFPI activity and F1 + 2 levels were significantly higher, while ETP, prothrombin antigen levels, and antithrombin activity were lower as compared to the controls. In IDDM patients with microalbuminuria, a manifestation of generalized angiopathy, TFPI activity, F1 + 2 and thrombomodulin levels were higher than in patients with only retinopathy or patients without complications. No correlation between TFPI activity, F1 + 2 levels and thrombomodulin was found, while TFPI activity was negatively correlated with ETP (r = -0.27). Microalbuminuria was significantly correlated with TFPI activity (r = 0.46), F1 + 2 (r = 0.56), and thrombomodulin (r = 0.52). In TFPI-depleted plasma, ETP increased, indicating that ETP is affected by TFPI. In conclusion, the increase in TFPI activity in IDDM patients may not be considered to be a reaction on a procoagulant state. It is hypothesized that vascular damage, leading to alterations in glycosaminoglycans, is in part responsible for the changes in TFPI activity, F1 + 2 levels and ETP.
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PMID:Increased tissue factor pathway inhibitor (TFPI) and coagulation in patients with insulin-dependent diabetes mellitus. 906 96

We investigated the usefulness of the fluorogenic prothrombin time (FPT) for detection of hypercoagulability and its association with hyperlipidemia in 19 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 healthy control subjects, compared with plasma levels of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and D-dimer. We also evaluated the effect of bezafibrate on hypercoagulability in 10 hyperlipidemic NIDDM patients. The plasma levels of FPT and fibrinogen were significantly higher in hyperlipidemic NIDDM patients than in normolipidemic NIDDM patients and controls. Plasma levels of PAI-1 and D-dimer were significantly higher in normolipidemic and hyperlipidemic NIDDM patients compared with controls. The FPT was correlated with the HbA1c, the body mass index, and levels of total cholesterol, fibrinogen and PAI-1. Six-months therapy with bezafibrate reduced the levels of FPT, triglycerides and basal insulin, but did not alter levels of fibrinogen, PAI-1 and D-dimer. Our results showed that the FPT was useful for detection of hypercoagulability and evaluation of the effect of drugs. The increased FPT in patients with NIDDM suggested that hypercoagulability was present in association with hyperlipidemia.
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PMID:Effect of bezafibrate on hypercoagulability assessed by fluorogenic prothrombin time in hyperlipidemic patients with non-insulin-dependent diabetes mellitus. 921 24


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