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)

The mechanisms by which insulin deficiency affects muscle glucose transport were investigated. Epitrochlearis muscles from rats with streptozotocin-induced diabetes and from controls were incubated in vitro for 0.5-14 h. The incubation was shown not to impair muscle energy stores or tissue oxygenation. Diabetes decreased basal 3-O-methylglucose transport by 40% (p less than 0.01), and insulin-stimulated (20 milli-units/ml) glucose transport capacity by 70% (p less than 0.001). In vitro incubation gradually normalized insulin responsiveness (3.77 +/- 0.38 before versus 8.97 +/- 0.65 mumol X ml-1 X h-1 after 12 h of incubation). Basal glucose transport remained significantly reduced. The reversal of the insulin responsiveness did not require the presence of rat serum and, furthermore, took place even in the absence of insulin. In fact, insulin responsiveness was higher after incubation (14 h) with no insulin than with 100 microunits/ml insulin (9.85 +/- 0.59 versus 8.06 +/- 0.59 mumol X ml-1 X h-1, p less than 0.05). Glucose at 30 mM did not affect the normalization of the insulin-stimulated glucose transport capacity, whereas incubation in serum from diabetic rats resulted in a slightly (26%) blunted reversal (7.60 +/- 0.39 versus 8.89 +/- 0.45 mumol X ml-1 X h-1 with diabetic versus control serum for 14 h, p less than 0.05; before incubation the value was 3.87 +/- 0.40). Inhibition of protein synthesis by cycloheximide blocked the normalization by 80%. These results suggest the presence in diabetic serum of some labile factor that might inhibit the glucose transport system. The results indicate that the decreased insulin-stimulated glucose transport capacity, in the insulin-deficient diabetic muscle, is not a direct consequence of the lack of insulin or of high glucose concentrations.
 ...
PMID:Reversibility of decreased insulin-stimulated glucose transport capacity in diabetic muscle with in vitro incubation. Insulin is not required. 329 36

Several studies suggest an association between the use of third-generation oral contraceptives (OCs) containing either desogestrel or gestodene and an increased risk of venous thromboembolism. Current users of third-generation OCs faced about a two-fold increased risk of thromboembolism than users of other OCs, even after researchers controlled for possible confounding factors that increase the risk for thromboembolism, e.g., smoking. These latest findings suggest that these OCs actually induce the increased risk of thromboembolism. One study showed that body mass index did not account for the added risk of thromboembolism to users of third-generation OCs. Another study found that family history of venous thrombosis did not increase the risk in third-generation OC users. It did find that nulligravidity and the factor V Leiden mutation contributed to the increased risk of venous thromboembolism in third-generation OC users. Health professionals should consider the size of both risks and benefits linked to various OCs when advising women to discontinue or not to begin using third-generation OCs. The increased risk of venous thromboembolism linked to a third generation OC, beyond that linked to the use of an earlier OC, is 10-15/100,000 woman-years of use. Assuming a typical case fatality rate of around 1%, the increased rate of fatal thromboembolism would range from 1 to 1.5/million woman-years. One study found that mortality from vascular diseases among current users of third-generation OCs is essentially the same as that of users of other OCs. No studies have examined any possible benefits from third-generation OC use in terms of incidence and mortality related to myocardial infarction or diabetes mellitus. Women and their health providers need to make their decision by weighing an increase, albeit small, in thromboembolism-related death against a possible decrease in the risk of other serious conditions.
 ...
PMID:Third-generation oral contraceptives: how risky? 750 Jul 51

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.
 ...
PMID:The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. 918 84

Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
 ...
PMID:Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C. 943 45

Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in design and did not consider the existence of pathologically distinct processes. The Bruneck Study is a prospective survey in the general community (age range, 40 to 79 years). The baseline examination and first reevaluation were performed in the summers of 1990 and 1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and advanced (incidence and/or progression of stenosis >40%) stages of atherogenesis were differentiated. The risk profile of early atherogenesis consists of traditional risk factors, such as hypertension, hyperlipidemia, and cigarette smoking (pack-years), supplemented by a variety of less well-established risk conditions, including high body iron stores, hypothyroidism, microalbuminuria, and high alcohol consumption. In contrast, the risk profile of advanced atherogenesis includes markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and clinical conditions known to interfere with coagulation: high fibrinogen, low antithrombin, factor V Leiden mutation, lipoprotein(a) >0.32 g/L, high platelet count, cigarette smoking, and diabetes. Hyperlipidemia and hypertension were of only minor relevance. These findings, along with the epidemiological features of advanced atherogenesis and emergence of an elevated fibrin turnover, suggest atherothrombosis to be a key mechanism in the development of advanced stenotic atherosclerosis. Supplementary 6-category logistic regression models illustrate the changing association between major risk predictors and atherosclerosis of increasing severity and substantiate appropriateness of the 40% threshold applied for the definition of advanced stenotic atherosclerosis. Atherosclerosis is a heterogeneous process that subsumes etiologically and epidemiologically distinct disease entities. The multifactorial etiology of atherosclerosis, which goes far beyond the traditional risk factors, has not yet achieved adequate attention in clinical practice and disease prevention.
 ...
PMID:Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study. 1066 53

Central retinal vein occlusion is one of the most common retinal vascular disorders. Few and contrasting data are available on the prevalence of hemostatic risk factors in patients with central retinal vein occlusion. The aim of this study was to investigate the most common hemostasis-related inherited risk factors for venous thrombosis in a group of 53 central retinal vein occlusion patients (median age 59 years, range 18-77 years) and in 53 comparable control subjects (median age 57 years, range 22-84 years). No difference was found in antithrombin III, protein C and protein S plasma levels between patients and controls. At univariate analysis, activated protein C resistance (odds ratio 5.8) and factor V Leiden (odds ratio 4.4) were significantly associated with central retinal vein occlusion whereas G20210A polymorphism of the prothrombin gene was not. After adjustment for sex, age, and the other classic vascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking) activated protein C resistance remained the only independent risk factor for central retinal vein occlusion (odds ratio 11.5). These data indicate that activated protein C resistance may play a role in the pathophysiology of central retinal vein occlusion.
 ...
PMID:Activated protein C resistance is a risk factor for central retinal vein occlusion. 1105 59

The aim of this study was to assess, comprehensively, medical and genetic attributes of venous thromboembolism (VTE) in a multiracial American population. The Genetic Attributes and Thrombosis Epidemiology (GATE) study is an ongoing case-control study in Atlanta, Georgia, designed to examine racial differences in VTE etiology and pathogenesis. Between 1998 and 2001, 370 inpatients with confirmed VTE, and 250 control subjects were enrolled. Data collected included blood specimens for DNA and plasma analysis and a medical lifestyle history questionnaire. Comparing VTE cases, cancer, recent surgery, and immobilization were more common in caucasian cases, while hypertension, diabetes, and kidney disease were more prevalent in African-American cases. Family history of VTE was reported with equal frequency by cases of both races (28-29%). Race-adjusted odds ratios for the associations of factor V Leiden and prothrombin G20210A mutations were 3.1 (1.5, 6.7) and 1.9 (0.8, 4.4), respectively. Using a larger external comparison group, the odds ratio for the prothrombin mutation among Caucasians was a statistically significant 2.5 (1.4, 4.3). A case-only analysis revealed a near significant interaction between the two mutations among Caucasians. We found that clinical characteristics of VTE patients differed across race groups. Family history of VTE was common in white and black patients, yet known genetic risk factors for VTE are rare in African-American populations. Our findings underscore the need to determine gene polymorphisms associated with VTE in African-Americans.
 ...
PMID:The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE Study. 1287 43

Central retinal vein occlusion is associated with systemic conditions, such as arterial hypertension, diabetes, hypercholesterolemia, but also with certain hypercoagulability states (thrombophilia). Growing evidence indicates, that the presence of antiphospholipid antibodies and elevated plasma homocysteine levels predispose to central retinal vein occlusion. In younger patients, factor V Leiden (Arg506Gln) could increase the risk of this disease. Other probable causes of thrombophilia related to retinal vein occlusion include increased levels of plasminogen activator inhibitor 1 and lipoprotein (a), which impair fibrinolysis.
 ...
PMID:[Thrombophilia as a risk factor for central retinal vein occlusion]. 1455 91

The resistance to activated protein C (APC-resistance) based on the presence of factor V Leiden (F V Leiden) is the most frequent thrombophilic condition in the white race population. It contributes to the origin of thrombosis especially in the venous part of blood vessels. Significant geographic differences have been detected within Europe. The aim of this retrospective study was to determine the frequency in the occurrence of F V Leiden: 1. in healthy (asymptomatic) Slovak population, 2. in their consanguineously unrelated members with thrombosis and 3. in patients with myocardial infarction (IM) without or with other known risk factors of this disease (nicotinism, obesity, hypertension, dyslipoproteinemia, diabetes mellitus), respectively. The detection of FV Leiden was made by molecular biology methods. The occurrence in a group of 152 healthy individuals was four % (6 persons) and this frequency corresponds to the geographic localization of the Slovak Republic in Europe. In a group of 349 patients with thrombosis in anamnesis, FV Leiden was detected in 103 persons (29.5%). The occurrence was higher than the usually reported incidence in these patients (20%). Likewise, in a group of 35 patients with IM without risk factors in anamnesis, the occurrence of FV Leiden (8.6%) was significantly higher in comparison with healthy population and the incidence further increased significantly in a group of 41 patients with IM and the presence of at least one risk factor (14.6%). The authors therefore suppose an active role of the Leiden mutation of FV gene in the pathogenesis of this disease.
 ...
PMID:[Factor V Leiden and the Slovak population]. 1468 80

Renal transplantation improves survival and quality of life for patients with end-stage renal disease (ESRD). Improvements in immunosuppressive therapy have reduced early allograft loss due to acute rejection to very low levels. Early allograft loss, due to acute thrombotic complications, remains a constant and proportionally increasing complication of renal transplantation. Identifying risk factor(s) for thrombosis amenable to preventive strategies has been elusive. Epidemiological studies have attempted to define risk in terms of modifiable (drugs, dialysis modality, surgical procedure) and non-modifiable (age, diabetes mellitus, vascular anomalies) factors, or identify changes in coagulation or fibrinolysis promoting a more thrombotic state. Most recently the evolution of thrombophilia research has established the potential for inherited hypercoagulability to predispose to acute allograft thrombosis. Inheritance of the factor V Leiden (FVL), prothrombin G20210A mutation, or the presence of antiphospholipid antibodies (APA) may increase the risk of renal allograft thrombosis approximately 3-fold in selected patients. Patients with ESRD due to systemic lupus erythematosus (SLE) appear at particularly high risk of thrombosis, especially if they have either APA or detectable beta(2)-glycoprotein-1. Data for other hypercoagulable states such as hyperhomocystinemia or the C677T polymorphism of the methylenetetrahydrofolate reductase gene are deficient. Patients with APA, FVL, or prothrombin G20210A mutation also appear to have greater graft loss due to vascular rejection, possibly reflecting immunological injury upon the vascular wall exacerbated or induced by the prothrombotic state. While substantial in vitro data suggest cyclosporine is prothrombotic, an independent clinical association with allograft thrombosis is unproven. Interventions to reduce thrombotic risk including heparin, warfarin, and aspirin have been evaluated in both selected high-risk groups (heparin and warfarin) and unselected populations (heparin and aspirin). In unselected patients at low clinical risk, aspirin (75-150 mg/day) with or without a short period of unfractionated heparin (5000U twice a day for 5 days) appears to reduce the risk of renal allograft thrombosis significantly with a low risk of bleeding, especially when compared with low molecular weight heparins which risk accumulation in renal failure. In high-risk groups (identified thrombophilic risk factor, previous thrombosis, or SLE) longer period of heparin, with or without aspirin and maintenance with warfarin, should be considered. Re-transplantation following graft loss due to vascular thrombosis can be undertaken with a low risk of recurrence. Further prospective studies evaluating both putative risk factors and intervention strategies are required to determine whether routine clinical screening for thrombophilic factors is justified.
 ...
PMID:Hypercoagulability in renal transplant recipients. Identifying patients at risk of renal allograft thrombosis and evaluating strategies for prevention. 1513 66


1 2 3 4 Next >>