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)

We measured the plasma levels of fibrinogen, D-dimer, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (SFM), tissue-type plasminogen activator (t-PA) and thrombomodulin (TM) in patients with non-insulin-dependent diabetes mellitus (NIDDM). There were no significant differences in the hemostatic parameters between the 77 patients with NIDDM and healthy control subjects, although the plasma levels of fibrinogen, D-dimer, TAT, and PPIC in the NIDDM patients were slightly higher than those in the healthy controls. Among the NIDDM patients divided into three groups by the urinary albumin excretion (UAE) level, there was no significant difference in age or sex among the normo-, micro-, and macroalbuminuria groups, and the HbA1C level in the micro- and macroalbuminuria groups were slightly higher than those in the normoalbuminuria group. There was no significant difference in activated partial thromboplastin time, prothrombin time, fibrinogen, TAT, PPIC, D-dimer, or t-PA among these three groups. The plasma SFM and TM levels in the macroalbuminuria group were significantly higher than those in the normo- and microalbuminuria groups. The relationships between HbA1C and the hemostatic parameters were poor, but the plasma TM and SFM levels were significantly correlated with the urine albumin index.
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PMID:Increased soluble fibrin monomer and soluble thrombomodulin levels in non-insulin-dependent diabetes mellitus. 928 95

Changes in coagulation and fibrinolysis in the plasma (in vivo) and hepatocytes (ex vivo) were studied using hyperglycemic rats. Hyperglycemia was induced by intravenous injection of 50 mg/kg streptozotocin (STZ). Eight weeks after the injection, we observed increases in thrombin-antithrombin III complex and tissue type plasminogen activator activity, decreases in plasma levels of antithrombin III, plasminogen and alpha2-plasmin inhibitor, and significant shortening of activated partial thromboplastin time. In freshly isolated or cultured hepatocytes from STZ-induced hyperglycemic rats, concentrations of proteins related to coagulation were increased. An increase in alanine-aminotransferase leakage and decreases in the levels of amylase, triglycerides and phospholipids were observed in the culture medium of hepatocytes from STZ treated rats. In vivo study revealed that STZ-induced subchronic diabetes induced imbalance between coagulation and fibrinolysis, and ex vivo study in hepatocytes from STZ-treated rats showed membrane degeneration and reduction in amylase synthesis, while protein synthesis related to coagulation was not inhibited. These results suggest that, despite vulnerability of liver cells from STZ treated rats, coagulation activity in the liver is retained and rather enhanced in STZ-induced hyperglycemic rats, which may contribute to the promotion of atherosclerosis.
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PMID:Blood coagulability and fibrinolysis in streptozotocin-induced diabetic rats. 958 51

During an 8-year period, 32 consecutive patients with chronic renal failure on maintenance hemodialysis were diagnosed to have cerebral hemorrhage. The outcome was determined using the activity of daily life (ADL) at 6 months after hemorrhage. The overall mortality was 64%. Of the 12 surviving patients, no one made a good recovery (back to normality), 5 recovered to ADL grade II, 4 to grade III, 1 to grade IV, and 2 to grade V. Up to 91% of the patients had a history of hypertension. On admission, Glasgow coma scale (GCS) was 15 in 8 cases, 8-14 in 10, and below 8 in 14. The poor prognostic factors showing statistical significance included a poor admission GCS, age above 65 years, and blood sugar level of more than 200 mg/dl. Other factors which apparently were not related to the outcome included sex, history of stroke, acute myocardial infarction, hypertension, and diabetes mellitus, the locations of hemorrhage, the duration of hemodialysis, treatment modality (surgery vs non-surgery), and the laboratory data (blood urea nitrogen, creatinine, platelet count, hemoglobin, prothromin time, and partial thromboplastin time). This study confirmed a poor prognosis for hemodialysis patients with cerebral hemorrhage. More attention should be paid to the control of blood sugar in this group to improve the outcome of cerebral hemorrhage in hemodialysis patients, especially in elderly patients with poor admission GCS.
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PMID:Prognosis of spontaneous intracerebral hemorrhage in hemodialysis patients. 1051 65

The purpose of this study was to examine the associations of carotid artery intima-media wall thickness (IMT) with hemostatic proteins and cardiovascular risk factors (CVRFs) in participants with and without non-insulin dependent diabetes mellitus (NIDDM). IMT measurements were determined by high resolution B-mode ultrasound imaging of the carotid arteries in 921 participants with NIDDM and 11,964 non-diabetic participants aged 45-64 years. Fasting glucose, serum lipids and activated partial thromboplastin time, factor VIII fibrinogen, factor VII, antithrombin III, protein C, and von Willebrand factor measurements were made. Compared to non-diabetic participants, participants with NIDDM had a more adverse pattern of CVRFs and a more procoagulatory profile. Participants with NIDDM had 0.06 mm (8.1%) higher mean IMT compared to non-diabetic participants after adjusting for age and gender (P < 0.001). However, only plasma fibrinogen concentrations showed statistically significant positive associations with IMT in both groups. After adjusting for CVRFs and fibrinogen, mean IMT remained 0.04 mm (5.4%) higher in diabetic compared to non-diabetic participants. Despite the more procoagulatory profile in participants with NIDDM, only plasma fibrinogen concentrations were independently associated with mean IMT. The association of NIDDM with mean IMT was only partly explained by CVRFs.
Diabetes Res Clin Pract 2000 Jan
PMID:Haemostasis and carotid artery wall thickness in non-insulin dependent diabetes mellitus. 1066 Feb 18

There is overwhelming evidence that platelets from diabetic individuals are hyperreactive, not only when microvascular complications are apparent, but already at an early stage of the disease. There is still controversy about the question of whether primary hyperreactive platelets may contribute to the origin or progression of microangiopathy or whether diabetic platelet hyperfunctionality is just a logical consequence of a continuous low-grade activation of platelets by contact with a diseased microvascular wall. As a consequence of platelet activation, the outer layer of its phospholipid membrane is more procoagulant than in the quiescent state, stimulating thrombin formation in plasma. This platelet function is called platelet procoagulant activity. We studied platelet prothrombinase activity (PPA), a final pathway platelet procoagulant activity of type 1 diabetic platelets, and looked for an eventual correlation with microvascular disease (background retinopathy) and mean platelet volume (MPV). Stypven clotting times (SCTs), reflecting PPA expression, and MPV of citrated platelet-rich plasma (PRP), were measured in 21 patients with type 1 diabetes-10 with and 11 without background retinopathy-under clinically acceptable metabolic control and compared them to 20 disease-free voluntary controls. We also compared PPA expression and MPV in diabetic individuals with and without retinopathy. With the SCT, a selective test adapted for studying PPA in PRP, we found hyperexpression of PPA in all diabetic patients. We found no difference in MPV between diabetic and control PRP. Comparing patients with and without background retinopathy we found no significant difference in PPA expression. From these results, we suggest that the phospholipid surface of diabetic platelets, more than the surface of normal control platelets, stimulate the expression of PPA. This diabetic platelet coagulant anomaly was not related to an increased platelet mass (higher MPV) nor to the presence of microangiopathy. We conclude that PPA hyperexpression is associated with patients with type 1 diabetes, already occurring in an early stage of the disease, and not necessarily a consequence of early-stage microvascular disease, because the anomaly is also demonstrable, in the same degree, in patients with diabetes without microangiopathy.
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PMID:Platelet prothrombinase activity, a final pathway platelet procoagulant activity, is overexpressed in type 1 diabetes: no relationship with mean platelet volume or background retinopathy. 1077 23

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.
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PMID:Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats. 1089 50

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on the development of diabetes, insulin resistance, and abnormalities of blood coagulation in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After 8-month oral EPA-E treatment, the incidence of diabetes at a dose of 0.1, 0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence was suppressed significantly and dose-dependently at a dose of 0.3 g/kg or higher compared with the rate (100%) for the vehicle control. Additionally, EPA-E significantly and dose-dependently decreased the elevation of plasma glucose after an oral glucose load and increased the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle control. Furthermore, EPA-E significantly and dose-dependently ameliorated coagulation-related parameters, including the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, and factor II, V, VII, VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and fibrinolysis-related parameters, including plasminogen, tissue-type plasminogen activator (t-PA), alpha2-plasmin inhibitor (alpha2-PI), and plasminogen activator inhibitor (PAI), and also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol to phospholipid (C/P) molar ratio in platelet membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple actions of the product in these laboratory animals. These include changes in platelet function, coagulation/fibrinolysis factors, plasma immunoreactive insulin secretion, and plasma glucose/insulin resistance.
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PMID:Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats. 1091 4

The majority of patients with acute coronary syndromes have renal impairment from either the aging process or from underlying disease, such as nephrosclerosis or diabetes. For example, in the phase 3 studies of bivalirudin use in PTCA, only 25% of patients had normal renal function: 46% had mild renal impairment, 28% had moderate renal impairment and about 1% had severe renal impairment. In patients with normal renal function, the intravenous pharmacokinetics of bivalirudin are dose proportional (linear) and are characterized by rapid plasma clearance (4.58 ml/minute/kg), a small volume of distribution (0.2 L/kg), and an elimination half-life of about 30 minutes. Renal clearance is the primary route of elimination of bivalirudin. As for other small polypeptides, bivalirudin is filtered at the glomerulus, secreted in the proximal convoluted tubule, reabsorbed in the distal convoluted tubule and degraded within intracellular lysosomes to constituent amino acids. There is a direct positive relationship between the dose of bivalirudin, plasma concentrations and the activated partial thromboplastin time (aPTT) or activated clotting time (ACT). A study comparing the pharmacokinetics and pharmacodynamics of bivalirudin with normal renal function (GFR greater than or = 90 ml/minute; n = 8), mild (GFR 60-89 ml/minute; n = 8), moderate (GFR 30-59 ml/minute; n = 7), or severe (GFR < 30 ml/minute; n = 10) renal impairment showed that while clearance was similar in the normal (4.58 ml/minute/kg) and mildly impaired (4.94 ml/minute/kg) groups, the clearance rate was reduced 45% in the moderate impairment (2.50 ml/minute/kg) group and about 68% in the severe impairment (1.46 ml/minute/kg) group. Clearance was further reduced (77%) in a group of 12 dialysis dependent patients (1.04 ml/minute/kg). There was a strong positive correlation between plasma bivalirudin concentrations and aPTT. The derived maximal effect (Emax) was similar for the normal (58.3 seconds), mildly impaired (44.7 seconds) and moderately impaired (56.8 seconds) groups, but prolonged in the severely renally impaired (79.4 seconds) and dialysis dependent (84.4 seconds) patients. These kinetic and dynamic results have recently been substantially confirmed in patients undergoing percutaneous transluminal coronary angioplasty (PTCA), where reduced plasma clearance (20%) and elevated ACTs were observed in patients with moderate renal impairment. The bleeding results of the phase 3 PTCA clinical trial (involving 4,312 patients) in which patients were classified as having normal renal function, or mild, moderate or severe renal impairment (using the above criteria), is consistent with the pharmacokinetic data. The incidence of major bleeding was directly correlated with renal function for both bivalirudin (normal, 1.2%; mild, 1.9%; moderate, 6%; severe, 0%) and heparin (normal, 3.1%; mild, 8.5%; moderate, 12.7%; severe, 26.7%). Importantly, the incidence of major bleeding was significantly less on bivalirudin than heparin in patients with any degree of renal impairment. The mean 45-minute ACT values were similar (350-400 seconds) in the normal, mild and moderately impaired groups, but elevated in the severely impaired group (450 seconds). A multivariate analysis of bleeding covariates in this database indicated that GFR is an important risk factor for bleeding (r(2) = 0.054), and accounted for twice the variability in bleeding as either sex or age.
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PMID:The use of bivalirudin in patients with renal impairment. 1115 32

This study assessed the pharmacokinetics, safety and efficacy of intravenous enoxaparin in patients undergoing percutaneous coronary intervention (PCI). Sixty consecutive patients [(age, 62 11 years; female, 16%; diabetes, 18%; hypertension, 53%; prior myocardial infarction (MI), 43%] undergoing PCI (stable angina, 89%; stent, 92%; two-vessel disease, 23%; B2/C lesions, 45%) were administered intravenous enoxaparin 1 mg/kg for procedural anticoagulation. Blood samples for anti-Xa level and activated partial thromboplastin time (aPTT) were assayed from the first 20 patients before and after enoxaparin administration at the following intervals: 5, 30, 60, 90, 120, 150, 180, 210, 240, 360 and 480 minutes. Activated clotting time was assessed 5 minutes after enoxaparin administration. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. All patients were monitored for adverse clinical events at clinic visit 4 8 weeks after hospital discharge. No TIMI major or minor bleedings occurred during hospitalization for the PCI (median stay post-PCI = 1 day). One patient (2%) developed a non-Q wave MI after the PCI and before hospital discharge. There was no death or urgent revascularization up to clinical follow-up. The peak anti-Xa level was 1.30 0.18 IU/ml (range, 1.03 1.69 IU/ml). The minimum anti-Xa level was 0.55 IU/ml 4 hours after enoxaparin. Thus, the use of intravenous enoxaparin in patients undergoing PCI is associated with a low incidence of ischemic and bleeding complications. A stable therapeutic anticoagulant effect is provided without the need for monitoring within 4 hours of enoxaparin administration.
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PMID:Stable and optimal anticoagulation is achieved with a single dose of intravenous enoxaparin in patients undergoing percutaneous coronary intervention. 1214 72

During myocardial infarction (MI), high levels of circulating procoagulant microparticles (MP) shed from endothelial cells and platelets diffuse prothrombotic and proinflammatory potentials crucial for the coronary prognosis. In addition to conventional treatments, we evaluated whether vitamin C treatment could modify circulating levels of procoagulant MP. Upon admission, 61 patients with MI were prospectively randomized for immediate additional vitamin C treatment. Circulating MP were quantified by functional prothrombinase assay before and after 5 days of vitamin C administration (1 g day-1). The cellular origin of MP was also assessed. In vitamin C-treated patients, the reduction in platelet-derived MP was 10% higher (P = 0.01). In patients with diabetes mellitus, dyslipidemia or more than two cardiovascular risk factors, vitamin C decreased endothelial and platelet-derived MP levels by approximately 70% and 13%, respectively. This early effect on circulating platelet and endothelial-derived MP, testifies to the importance of oxidative stress during MI. Vitamin C could prove beneficial for the outcome of patients at higher thrombotic risk.
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PMID:Protective effects of vitamin C on endothelium damage and platelet activation during myocardial infarction in patients with sustained generation of circulating microparticles. 1287 55


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