Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic nephropathy, a major complication of diabetes mellitus that leads to mortality, has been shown to involve a dysregulation of the coagulation system. Annexin-2, a co-receptor for plasminogen and tissue plasminogen activator on endothelial cells, is one of the molecules required to maintain the antithrombogenic properties of endothelial cells. Previously, we showed that recombinant annexin-2 protein (rAN II) modulated impaired fibrinolytic activity in the carotid arteries of rats. In the present study, to investigate its protective effects against diabetic nephropathy, rAN II was administered to KK-Ay mice, a murine model of type 2 diabetes, for eight weeks, and albuminuria, kidney size, and histological glomerular lesions were investigated. The mean weight of kidneys from KK-Ay mice treated with rAN II was significantly less than that of those treated with PBS (control) (p < 0.02). Furthermore, the level of albuminuria observed in rAN II-treated KK-Ay mice was significantly less than that of the control group (rAN II, 0.90+/-0.12 microg/day; PBS, 1.55+/-0.31 microg/day; p < 0.01); also, the area of diffuse glomerular lesions was significantly smaller (rAN II, 41.51+/-4.54%; PBS, 81.81+/-8.10%; p < 0.01). Bleeding time, prothrombin time (PT), and active partial thromboplastin time (APTT) did not significantly differ between the two groups. Our results suggest that rAN II may inhibit the progression of diabetic nephropathy in KK-Ay mice without influencing the coagulation system, indicating that annexin-2 may be considered as a possible new therapeutic tool for patients with diabetic nephropathy.
 ...
PMID:Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability. 1720 Jul 79

Diabetes mellitus is considered to cause a tendency for arterial thrombosis. Recent studies addressed the association between venous and arterial disease. Resistance to activated protein C is one of the most common causes of venous thrombosis and linked to a single point mutation in the factor V gene, designated as factor V Leiden mutation. There is little information regarding the status of factor V Leiden mutation in type 1 diabetes. The aim of this study is to evaluate association among activated protein C sensitivity ratio, factor V Leiden mutation, and type 1 diabetes taking into account metabolic control, lipids and diabetic complications. The study population consisted of 47 healthy subjects (27.9 +/- 1.2 years) and 48 type 1 diabetic patients (27.9 +/- 1.1 years). Activated protein C sensitivity ratio was measured by activated partial thromboplastin time based assay. The presence of factor V Leiden mutation was determined by amplifying the fragments encompassing gene mutation by PCR. Mean normalized activated protein C sensitivity ratio values and prevalence of heterozygous factor V Leiden mutation were not significantly different between groups (1.08 +/- 0.03 and 6.3% in healthy subjects; 1.01 +/- 0.03 and 6.4% in type 1 diabetic patients, respectively). The activated protein C sensitivity ratio and factor V Leiden mutation were not found to be linked with metabolic control parameters, lipids and diabetic complications in type 1 diabetic patients. There was no association among factor V Leiden mutation, activated protein C sensitivity ratio and type 1 diabetes, metabolic control parameters as well as complications of diabetes. Although the propensity to thrombosis is increased in individuals with type 1 diabetes, activated protein C sensitivity ratio and factor V Leiden mutation do not appear to be significant determinants.
 ...
PMID:Factor V Leiden mutation and type 1 diabetes mellitus. 1818 Jun 19

In Singapore in 2005 there were 14,209 documented cases of dengue fever, including 25 deaths. The epidemiology of dengue in Singapore is changing, with increasingly severe infection in adults with chronic disease being recognised. We performed a retrospective review of nine adult patients who died of dengue-related illness from 1 December 2004 to 30 November 2005 at the National University Hospital. The diagnosis was initially missed in six of the nine patients due to an atypical presentation. All the patients had significant comorbid conditions; six of the nine had diabetes mellitus. Altered mental state preceded frank shock in eight of the nine patients. Secondary bacteraemia was a contributor to death in four. Derangement of laboratory features such as prothrombin time, activated partial thromboplastin time and serum albumin level was common on presentation. Transition countries such as Singapore have an increasingly advanced health system supporting an ageing population, yet are still at risk of community-acquired tropical infections. We have found that atypical presentations, comorbidities, secondary bacterial infection and abnormal serum markers at presentation may be predictors of death from dengue.
 ...
PMID:Dengue mortality: reassessing the risks in transition countries. 1924 2

We retrospectively evaluated dosing patterns and 37-day outcomes in argatroban-treated African American (n = 52), Asian (n = 13), and Hispanic (n = 14) patients with heparin-induced thrombocytopenia (HIT). The Asians required a lesser median dose (1.0 microg/kg/min) than the other groups (1.9 microg/kg/min, each) to achieve comparable activated partial thromboplastin times (medians: 61-69 s). Durations of therapy were similar (medians: 4.0-5.5 days). New thrombosis occurred in 11 (21%) African Americans, 1 (8%) Asian, and 1 (7%) Hispanic; of these 13 patients, 9 (69%) had baseline HIT-related thrombosis. Amputation occurred in 6 (12%) African Americans and 3 (21%) Hispanics; of these nine patients, 6 (67%) had diabetes. One (2%) African American and 1 (7%) Hispanic died from thrombosis. The composite of death due to thrombosis, amputation due to ischemic complications of HIT, or new thrombosis occurred in 14 (27%) African Americans, 1 (8%) Asian, and 4 (29%) Hispanics. Two (4%) African Americans and none others (0%) had major bleeding. These findings suggest that despite argatroban anticoagulation, African Americans and Hispanics may have worse outcomes in HIT than Asians. In minority patients with adverse HIT outcomes, baseline HIT-related thrombosis or diabetes is often present.
 ...
PMID:Dosing patterns and outcomes in African American, Asian, and Hispanic patients with heparin-induced thrombocytopenia treated with argatroban. 1901 11

A diabetic vasculature promotes cardiovascular diseases via endothelial cell activation induced by advanced glycation end products. It has recently become clear that activated platelets are a hallmark of cardiovascular disease and diabetes progression, by initiating and/or perpetuating the endothelial cell response. However, the role that platelets play in diabetic cardiovascular diseases remains elusive. Our objective was to evaluate the effects of glycated serum albumin on flow induced platelet activation and platelet aggregation. Albumin was glycated for up to 8 weeks. Timed samples of glycated or non-glycated albumin were removed to determine the effects of the extent of glycation on platelet functional changes. Thrombin receptor agonist peptide 6 (TRAP(6), residues 42-47 of the thrombin receptor) and collagen I induced platelet aggregation was measured as a time course of glycated albumin incubation. The thrombogenicity of platelets incubated with glycated albumin was also measured under static and dynamic flow conditions using the modified prothrombinase assay. CD41 and CD62P expression was examined using flow cytometry to validate aggregation and activation studies. Platelets subjected to glycated albumin were more susceptible to TRAP(6)- and collagen-induced aggregation and flow induced activation. The extent of albumin glycation modulates these changes. As the albumin glycation time increased, this enhancement in platelet function was more pronounced. These results indicate that under diabetic conditions activated platelets may act to promote cardiovascular disease progression.
 ...
PMID:Glycated albumin modulates platelet susceptibility to flow induced activation and aggregation. 1943 39

The objective of this study was to validate a simple factor Xa-based clotting test developed to monitor procoagulant phospholipids (PPLs) and platelet-derived microparticles (PMPs). This assay is easily automated, giving it a major advantage over the more laborious and expensive flow cytometry, electron microscopy and ELISA techniques in general usage at present. The intra-assay and inter-assay variation coefficients were less than 5% at both low and high levels of PPLs. The test is not affected by other clotting factors is assured by the use of a phospholipid-free animal plasma, which provides excess factor V, fibrinogen and prothrombin. This test was evaluated in apparently healthy volunteers and in selected patient groups associated with increased levels of PMPs in the circulation (diabetes mellitus, sickle cell disease, thyroid cancer and patients with multiple trauma). The study showed that XaCT has a high discriminating power for PPLs and that the patient groups have significantly highly increased PPLs activities when compared with healthy volunteers. Although of a preliminary nature, the test has shown that it has the sensitivity for discriminating severity of disease, as it could detect patients in sickle cell crisis and differentiate between type 1 and 2 diabetes. In conclusion, the combination of reliability, reproducibility and easy performance makes the XaCT assay a simple test to screen for PPLs in plasma samples.
 ...
PMID:Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids. 1959 17

Atrial fibrillation (AF) requires anticoagulation for prevention of arterial embolism, especially in the presence of defined risk factors summarized in the CHADS (2) score (congestive heart disease, hypertension, age >75 years, diabetes, history of ischemic stroke or transient cerebral ischemia). Vitamin K antagonists as drugs of choice have several limitations. International normalized ratio (INR) adjustment to 2.0 to 3.0 may be difficult to maintain, and doses vary widely between patients. Inherited variations of the vitamin K epoxide reductase C1 enzyme and of the cytochrome P450 2C9 system influence the dosage as well as exogenous factors such as food and drug intake or intercurrent diseases. Increasing age and risk of falling are the main factors behind the underuse of anticoagulation in AF. Anticoagulants with a lack of all or most of these characteristics and without need of regular monitoring for dose adjustment may improve the adherence to the indication for anticoagulation. Indirect systemic and oral direct factor Xa and oral direct thrombin inhibitors are currently being developed for the prevention of embolism in patients with AF.
 ...
PMID:New anticoagulants in atrial fibrillation. 1978 62

The authors carried out a comparative analysis of the level of homocysteine and the state of haemostasis in patients with and without type 2 diabetes mellitus in the remote terms after endured reconstructive operations on the aorto-iliac segment. They examined a total of eighty-eight patients who had endured reconstructive operations on the aorto-iliac segment at various terms. Of these, forty-two patients were found to have a severe course of type 2 diabetes mellitus (59.9% with decompensation) and forty-six subjects without diabetes constituted the group of comparison. The average age of the patients amounted to 61.9 +/- 1.25 years, with all being smokers. The following parameters were assessed: patency of the bypasses and major arteries of the lower limbs (LL), homocysteine (Hey), fibrinolytic activity, fibrinogen, activated partial thromboplastin time (aPTT), factor XIII, thrombin time, prothrombin index, activity of antithrombin III (AIII), platelet aggregation with ADP, and glycosylated haemoglobin (Hb Aic).
 ...
PMID:[Assessment of the level of homocysteine and the state of haemostasis in patients with and without type 2 diabetes mellitus in remote terms after reconstructive operations on the aorto-iliac segment]. 1980 38

Antiphospholipid antibodies (aPL) are considered to be contributory factors in the development of thrombotic events. The objective of the study was to determine if aPL are involved in the pathogenesis of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. IgG anticardiolipin antibodies (IgG aCL), lupus anticoagulant (LA), and anti-IgG beta2-glycoprotein I antibodies (anti-beta2-GPI) were prospectively tested in 34 patients with DR (group 1), 20 males and 14 females, range of age 52-79 years, mean age 57 +/- 4.6 years, duration of diabetes 8-15 years, as compared to 29 type 2 diabetic patients without DR (group 2), 19 males and 10 females, range of age 54-77 years, mean age 58 +/- 4.8 years, duration of diabetes 10-13 years, and to 31 controls matched for age and sex (group 3). IgG aCL and anti-beta2-GPI were detected by enzyme-linked immunosorbent assay (ELISA) and LA was detected by activated partial thromboplastin time, kaolin clotting time, dilute Russell's viper venom time, dilute prothrombin time. Comparison between patients and controls and patients group were expressed as relative risk with its 95% confidence interval (RR [95%/CI], where a lower limit > 1.0 was considered significant. All values were determined by Fischer's exact test. A value of p < 0.05 was considered statistically significant. The incidence of IgG aCL positive (low 4-15 GPL U IgG aCL titers) in group 1 was 21/34 (62%) vs. 12/29 (41%) in group 2 (RR 1.460 95% CI [0.9052 to 2.382]), p = 0.1330. The incidence of LA positive in group 1 was 27/34 (79%) vs. 8/29 (28%) in group 2 (RR 3.086 95% CI [1.584 to 6.010]), p < 0.0001. The incidence of anti-IgG beta2-GPI positive in group 1 was 29/34 (85%) vs. 6/29 (21%) in group 2 (RR 4.640 95% CI [2.067-10.418]), p < 0.0001. The results suggest the possible participation of anti-beta2-GPI and LA in the pathogenesis of DR, shifting the hemostatic balance toward a pro-thrombotic state increasing the risk of developing thrombosis.
 ...
PMID:Study of antiphospholipid antibodies in type 2 diabetes mellitus with and without diabetic retinopathy. 2044 42

The development of hemostasis research at Karolinska Institutet is described, focusing first on the initial findings of the fibrinogen structure and the hereditary bleeding disorders, hemophilia A and von Willebrand's disease. Basic research has focused on new biomarkers for cardiovascular/thromboembolic disorders, such as myocardial infarction and stroke, including preeclampsia and diabetes, with studies on the importance of decreased fibrinolysis in these disorders. Since long, the structure of the fibrin network has been evaluated, and recently the influence of aspirin and new thrombin and factor Xa inhibitors has been investigated. Research on the contact pathway of coagulation has also started at the Unit.
 ...
PMID:Molecular aspects in clinical hemostasis research at Karolinska Institutet. 2049 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>