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)

Prothrombin activation requires the direct interplay of activated platelets and plasma clotting factors. Once formed, thrombin causes profound, irreversible activation of platelets and reinforces the platelet plug via fibrin formation. Delayed or deficient thrombin production increases bleeding risk. Commonly employed coagulation assays, the prothrombin and partial thromboplastin times, use clot formation as a surrogate marker of thrombin generation. These assays routinely utilize platelet-poor plasma and completely miss the effects of platelets. Other markers of thrombin generation, prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complex, are typically measured after the fact. We report a simple assay, which employs the onset of platelet contractile force (PCF) as a surrogate marker of thrombin generation. PCF generation occurs concomitant with the burst of F1 + 2 release. The time between assay start and PCF onset is termed the thrombin generation time (TGT). TGT is prolonged in clotting factor deficiencies and in the presence of direct and indirect thrombin inhibitors. TGT shortens to normal with clotting factor replacement and shortens with administration of recombinant factor VIIa. TGT is short in thrombophilic states such as coronary artery disease, diabetes and thromboangiitis obliterans and prolongs toward normal with oral and intravenous anticoagulants.
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PMID:Onset of force development as a marker of thrombin generation in whole blood: the thrombin generation time (TGT). 1294 Oct 40

This study was designed to examine the relationship of short activated partial thromboplastin time (aPTT) and prothrombin time (PT) to the incidence of thromboembolic events, hereditary and acquired coagulation defects associated with an increased risk of thrombosis, or cardiovascular diseases in patients undergoing renal transplantation. The prevalence of these conditions in our patients (n = 436) was 55%. Forty-two percent of the patients had short aPTT or PT. Multivariate analysis revealed that patients with short aPTT have an odds ratio (OR) = 2.15, 95% Confidence Interval (CI) (1.27-3.64) (p = 0.0042), and for patients with short PT, an OR = 2.01, 95% CI (0.99-4.08) (p = 0.052). Our study also suggests that other risk factors, including non-white ethnicity (98% blacks), OR = 1.64, 95% CI (1.01-2.67) (p = 0.047), diabetes mellitus, OR = 2.62, 95% CI (1.11-6.18) (P = 0.028), and autosomal dominant polycystic kidney disease (ADPKD) (p < 0.0001). Short aPTT results, or probably short PT results, pre- or post-transplantation may be associated with increased risks for thromboembolism.
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PMID:Thromboembolic risk factors in patients undergoing kidney transplant: implication of abnormally short activated partial thromboplastin time. 1458 52

Coagulative function of saliva derives from the thromboplastin found in saliva. It may establish hemostasis in the mouth. Salivary disfunction and changes in salivary composition and are frequent complications of diabetes. This study investigated the influence of some local etiologic and systemic factors on salivary thromboplastic activity (STA) in diabetics. In this study, cytological smears and biochemical tests were used. STA was measured by Quick's one stage method, serum glucose by the glucose oxidase method, and salivary protein by the method of Lowry. STA was almost the same in the diabetic and control groups. The only statistically significant difference within the diabetic group was found to be due to antibiotic usage. STA, i.e. clotting time, was 30% longer (114 s) ( p<0.05) and salivary protein (4.07 mg ml(-1)) ( p<0.1) was lower in diabetics not taking antibiotics than in those taking them. No such differences were observed in the healthy controls. Significant linear correlations ( p<0.05) with respect to STA were with salivary protein in the control group (r=0.61) and in the diabetic group (r=0.51) and with antibiotic usage (r=0.29), with leukocyte cell count (r=0.27) in the diabetic group. It can be concluded that salivary cells, proteins and antibiotic usage are important for STA.
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PMID:Salivary thromboplastic activity in diabetics and healthy controls. 1465 32

During myocardial infarction (MI), platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP were described in diabetes mellitus (DM), and could be of particular significance in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM) patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon thrombin cleavage. Variations were compared to values measured in healthy volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and quantified by prothrombinase assay. Their cellular origin was assessed. With respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of platelet-derived MP and the correlation between procoagulant MP and sGPV, testify to the central role of thrombin-activated platelets during MI in both DM and NDM subsets. The release of platelet and endothelial cell-derived MP persisted at D6 and was more important in DM, the associated prothrombotic risk being also reflected by higher levels of sGPV. The endothelial damage revealed by endothelial-derived MP was twice that observed in NDM patients. In DM patients presenting cardio-vascular events at 6 month follow-up, MP levels were significantly higher at D1 after MI than in those without complication (24.9 +/- 4.8 vs. 12.3 +/- 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP.
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PMID:Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus. 1496 Nov 63

The safety of glycoprotein (GP) IIb/IIIa inhibitors has been well documented in clinical trials. Although these trials have included a broad patient population, the strict enrollment criteria may have resulted in exclusion of patients at a higher risk of bleeding complications. The authors conducted a retrospective chart review of 1020 consecutive patients who received GP IIb/IIIa inhibitors and underwent percutaneous coronary intervention in a large community hospital. They used Thrombolysis in Myocardial Infarction (TIMI) criteria to define major or minor bleeding complications. Bleeding complications developed in 214 (21%) patients, with major bleeding in 89 (9%). Univariate predictors of bleeding were older age, lower body weight, elevated serum creatinine, higher activated partial thromboplastin time (aPTT) level, history of diabetes mellitus (DM), peripheral vascular disease (PVD), congestive heart failure (CHF), and emergency procedure for acute myocardial infarction (AMI). Multivariate predictors of major bleeding were PVD (20% in bleeding group vs 11% in nonbleeders, odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.2-2.6, P < .004), age (68 +/- 2 years, 95% CI = 66-70 in bleeding group vs 63 +/- 13 years, 95% CI = 61.2-63 in nonbleeders, P < .001), and higher aPTT level (66 +/- 27 seconds, 95% CI = 63-70 in bleeding group vs 53 +/- 28 seconds, 95% CI = 51-56 in nonbleeders, P < .001). The risk of bleeding in the large community hospital setting may be higher than in randomized clinical trials. This increased risk is associated with higher hospitalization costs. Recognition of predictors of bleeding should further enhance the safety of these antiplatelet agents.
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PMID:Glycoprotein IIb/IIIa receptor antagonists and risk of bleeding: a single-center experience in 1020 patients. 1549 51

Hypercoagulation often occurs in type 2 diabetes, suggesting pleiotropy of the genes that influence disease liability and hemostasis-related phenotypes. To better understand the relationship between hemostasis and diabetes, we first used maximum-likelihood methods to estimate the relative contribution of additive genetic, measured environmental, and shared household effects to the normal variance of 16 hemostasis-related traits in 813 individuals participating in the San Antonio Family Heart Study. We estimated moderate to high heritabilities (0.20-0.60) for each phenotype. Von Willebrand factor (VWF), thrombin activatable fibrinolysis inhibitor, activated protein C (APC) ratio, factor V, and prothrombin time had heritabilities greater than 0.50. The correlation between type 2 diabetes status and the hemostasis-related traits was then partitioned into genetic and environmental components using bivariate variance-components methods. Significant (p < or = 0.05) positive genetic correlations (0.37-0.51) occurred with factors II and VIII, VWF, total protein S (tPS), and tissue factor pathway inhibitor. Significant negative genetic correlations were estimated for activated partial thromboplastin time (-0.49) and APC ratio (-0.38). By contrast, significant environmental correlations occurred only with factor II (-0.40) and tPS (-0.31). Our results suggest that genes are important contributors to the normal variation in hemostasis-related traits and that genes influencing hemostasis-related traits pleiotropically influence diabetes risk.
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PMID:Heritability of hemostasis phenotypes and their correlation with type 2 diabetes status in Mexican Americans. 1611 12

Simvastatin, a widely used 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, effectively reduced cardiac death and ischemic events in patients with coronary heart disease (CHD) and diabetes mellitus (DM). The mechanism of cardiovascular benefits of statins in DM remains unclear. We examined how simvastatin influences the levels of several in vivo markers for coagulation and fibrinolysis in 26 Type 2 DM patients. The diabetic patients received 20 mg/day of simvastatin up to 12 months. The levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and triglycerides in peripheral circulation of patients were significantly reduced after > or =6 weeks of simvastatin treatment. Levels of prothrombin fragment 1+2 (F1+2), factor VII, plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI) antigens, but not tissue plasminogen activator (tPA) antigen, in the pre-simvastatin plasmas of the diabetic patients were significantly higher than the levels found in plasmas of healthy subjects. Significant reductions in F1+2 and PAI-1 levels were evident > or =6 weeks after the diabetic patients received simvastatin. Levels of total tPA, TFPI, FVII, hemoglobin A1c, fasting blood glucose, and insulin in the diabetic patients' plasma were not significantly altered by simvastatin treatment. Positive correlations were found between PAI-1 versus TC, PAI-1 versus LDL-c, and FVII versus triglycerides in the plasmas of simvastatin-treated patients. The results suggest that simvastatin reduces in vivo prothrombinase activity and PAI-1 levels in type 2 DM patients. These actions may contribute to the protective properties of simvastatin against ischemic events in diabetic patients.
Diabetes Res Clin Pract 2005 Nov
PMID:Impact of simvastatin on hemostatic and fibrinolytic regulators in Type 2 diabetes mellitus. 1618 73

Tissue factor (TF), formerly known as thromboplastin, is the key initiator of the coagulation cascade; it binds factor VIIa resulting in activation of factor IX and factor X, ultimately leading to fibrin formation. TF expression and activity can be induced in endothelial cells, vascular smooth muscle cells, and monocytes by various stimuli such as cytokines, growth factors, and biogenic amines. These mediators act through diverse signal transduction mechanisms including MAP kinases, PI3-kinase, and protein kinase C. Cellular TF is present in three pools as surface, encrypted, and intracellular protein. TF can also be detected in the bloodstream, referred to as circulating or blood-borne TF. Elevated levels of TF are observed in patients with cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking as well as in those with acute coronary syndromes. TF may indeed be involved in the pathogenesis of atherosclerosis by promoting thrombus formation; in addition, it can induce migration and proliferation of vascular smooth muscle cells. As a consequence, therapeutic strategies have been developed to specifically interfere with the action of TF such as antibodies against TF, site-inactivated factor VIIa, or recombinant TF pathway inhibitor. Inhibition of TF action appears to be an attractive target for the treatment of cardiovascular diseases.
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PMID:Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. 1646 45

Many factors are known to influence the unfractionated heparin (UFH) dosage required to achieve therapeutic anticoagulation, including weight, sex, age, tobacco smoking, and diabetes mellitus. However, no interaction between thyroid function and UFH has been documented. An 83-year-old Caucasian woman had active hyperthyroidism that appeared to significantly increase her dosage requirements for UFH. The patient had atrial fibrillation secondary to the hyperthyroidism. She had no known factors that would increase UFH requirements. A UHF dosage of 1400 U/hour was needed to achieve a therapeutic level of anticoagulation (activated partial thromboplastin time 62 sec). After she was treated for hyperthyroidism, her atrial fibrillation resolved and UFH was discontinued. On day 9 of her hospital admission, atrial fibrillation resumed, and the patient's thyroid function began to normalize. Unfractionated heparin was restarted, and this time therapeutic anticoagulation was achieved with only 800 U/hour. This patient's experience suggests a previously undocumented and clinically significant relationship between active hyperthyroidism and altered dosage requirements for UFH. Recognition of this potential interaction may shorten the time required for patients with hyperthyroidism to achieve therapeutic anticoagulation, thereby preventing complications associated with subtherapeutic anticoagulation.
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PMID:Possible effect of thyroid function on anticoagulant response to unfractionated heparin. 1646 35

Bivalirudin (Hirulog, Angiomax) is a specific, reversible and direct thrombin inhibitor with a predictable anticoagulant effect. It is cleared by both proteolytic cleavage and renal mechanisms, predominantly glomerular filtration. Bivalirudin inhibits both circulating thrombin and fibrin bound thrombin directly by binding to thrombin catalytic site and anion-binding exosite I in a concentration-dependent manner. Bivalirudin prolongs activated partial thromboplastin time, prothrombin time, thrombin time and activated clotting time (ACT). ACT levels with bivalirudin do not correlate with its clinical efficacy. Bivalirudin with a provisional GpIIb/IIIa inhibitor is indicated in elective contemporary percutaneous coronary intervention (PCI). In respect to combined ischemic and hemorrhagic endpoints of death, myocardial infarction, unplanned urgent revascularization and major bleeding during PCI (including subgroups of patients with renal impairment and diabetes) bivalirudin is not inferior to unfractioned heparin and planned GpIIb/IIIa inhibitors. In addition, bivalirudin has been consistently shown to have significantly less in-hospital major bleeding than heparin alone or heparin in combination with a GpIIb/IIIa inhibitor. Bivalirudin appears to be also safe and effective during PCI in patients with heparin-induced thrombocytopenia. Finally, data from PCI studies support the safety and efficacy of bivalirudin, although its direct randomized comparison with unfractionated heparin is lacking.
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PMID:Bivalirudin: pharmacology and clinical applications. 1661 33


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