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)

The Progetto Lombardo Atero-Trombosi (PLAT) Study was a prospective, multicenter, multidisciplinary study of the association among hemostatic variables, conventional risk factors, and atherothrombotic events in four groups of patients with preexisting vascular ischemic disease (335 myocardial infarction survivors, 123 patients with stable angina pectoris, 160 with transient ischemic attacks, and 335 with peripheral vascular disease). In the myocardial infarction group, univariate analysis showed that atherothrombotic events were associated with high fibrinogen (p = 0.001), factor VIII:C (p less than 0.001), and von Willebrand factor antigen (vWF:Ag) (p = 0.004) levels and with low high density lipoprotein cholesterol (p = 0.043), factor VII (p = 0.019), and protein C (p = 0.044) levels; multivariate analysis produced associations with high fibrinogen and factor VIII:C levels and low protein C levels. By both univariate and multivariate analysis, events in the angina pectoris group were associated with high vWF:Ag (p = 0.026) and leukocyte (p = 0.033) levels and the presence of carotid arterial stenosis (p = 0.063); associations with high leukocyte (p = 0.037) and factor VIII:C (p = 0.186) levels, family history (p = 0.031), and diabetes (p = 0.061) were also found in the group with transient ischemic attacks. In those with peripheral vascular disease, events were associated with Fontaine stage greater than or equal to IIB (p = 0.024), high factor VIII:C levels (p = 0.073), and low protein C (p = 0.028), fibrinogen (p = 0.030), antithrombin III (p = 0.054), and factor VII (p = 0.057) levels by univariate analysis and with Fontaine stage and low fibrinogen levels by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. PLAT Study Group. Progetto Lombardo Atero-Trombosi (PLAT) Study Group. 152 21

Diabetic patients have elevated plasma levels of factor VIII/von Willebrand factor (F VIII/vWF), and such elevations have been linked to vascular endothelial injury. In a prospective study we investigated the effect of metabolic regulation on the plasma levels of F VIII/vWF and cross-linked fibrin degradation products (XL-FDP), an indicator of intravascular coagulation, in 15 insulin-dependent diabetic patients who had no demonstrable vascular abnormalities. Eight patients had newly diagnosed diabetes, and 7 had been diabetic for an average of 12 yr. The patients were tested before and 1, 2, 4, and 8 weeks after the start of a structured diabetes education and care program, including introduction of a basal-bolus form of insulin treatment. Treatment for 8 weeks resulted in a highly significant improvement of metabolic control [hemoglobin Aic, 11.1 +/- 1.3% (+/- SD) vs. 6.8 +/- 1.0%; plasma fructosamine, 4.8 +/- 1.0 vs. 2.9 +/- 0.7 mmol/L; plasma glucose, 13.5 +/- 4.2 vs. 6.3 +/- 2.2 mmol/L; P less than 0.0001, respectively]. Compared to age- and sex-matched normal subjects, plasma activity of factor VIII (F VIII:C) was significantly elevated in the diabetic patients initially (1.5 +/- 0.6 vs. 1.0 +/- 0.1 x 10(3) U/L; P less than 0.01). After 2 weeks of intensified therapy it was 1.1 +/- 0.4 x 10(3) U/L. The mean plasma vWF value also was significantly elevated initially [vWF antigen, 1.8 +/- 0.7; normal group, 0.9 +/- 0.1 x 10(3) U/L (P less than 0.01); vWF ristocetin cofactor activity, 1.9 +/- 0.9; normal group, 1.0 +/- 0.3 x 10(3) U/L (P less than 0.001)] and decreased significantly after only 1 week of therapy. In the following 7-week period plasma vWF remained near normal. Plasma XL-FDP levels were elevated in all patients initially (190 +/- 150; normal group, 35 +/- 30 micrograms/L): the value was most abnormal in the patients with newly diagnosed disease (300 +/- 150 micrograms/L), indicating intravascular fibrin formation. The mean XL-FDP level declined significantly in the patients with newly diagnosed diabetes after 1 week of therapy; in the other patients, however, XL-FDP levels remained slightly elevated. In all 15 patients the plasma F VIII:C and XL-FDP levels were correlated significantly at all times. The plasma vWF and XL-FDP levels were correlated after 1, 2, 4, and 8 weeks of treatment as were the plasma vWF levels and glucose concentrations before and 1 and 2 weeks after the start of treatment program.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of near-normoglycemic control on plasma factor VIII/von Willebrand factor and fibrin degradation products in insulin-dependent diabetic patients. 265 19

Factor VIII (FVIII) and plasminogen activator activity (PAA) rise during hypoglycaemia, and this might contribute to the vascular complications of diabetes. Similar changes in haemostasis accompany raised plasma levels of vasopressin (aVP) and adrenaline. To investigate the effects of these hormones on haemostasis during hypoglycaemia and the role of plasma insulin concentrations, eight insulin-dependent diabetic patients underwent controlled hypoglycaemia for 20 min and 13 diabetic patients were investigated during hyperinsulinaemia with blood glucose maintained at 8.0 mmol/l. During hypoglycaemia, insulin levels increased to median values of 114 mU/l, a VP rose from 0.5 to 4.4 (p less than 0.005) pg/ml and adrenaline from 0.4 to 4.4 nmol/l (p less than 0.005). FVIII coagulant activity (FVIII:C) rose from 0.75 to 1.09 IU/ml (p less than 0.01) and the ristocetin co-factor (FVIIIR:Co) and von Willebrand factor antigen (vWF:Ag) showed similar responses. PAA increased from 156 to 745 units (p less than 0.005). During hyperinsulinaemia, insulin rose following infusion from 24 to 52 and 118 mU/l, maintained for an hour at each level. Despite this, plasma aVP, FVIII:C, FVIIIR:Co, vWF:Ag and PAA remained unchanged. This study indicates that the marked changes in FVIII, vWF and PAA concentrations which accompany hypoglycaemia depend on low blood glucose and not raised plasma insulin. The response in probably mediated by increases in adrenaline and aVP, which are part of the physiological response to hypoglycaemia.
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PMID:Hormonal control of haemostasis during hypoglycaemia in diabetes mellitus. 311 5

Patients with diabetes mellitus have higher levels of coagulation factor VIII than the non-diabetic population. This may be a result of poor metabolic control and could contribute to the development of microvascular complications. During ketoacidosis there are acute changes in plasma concentrations of coagulation factors, some of which may be mediated by the rise in vasopressin that occurs. We have investigated the effects of hyperglycaemia without ketosis on some aspects of haemostasis by manipulating blood glucose concentrations using a Biostator. After a 1h run-in period with the blood glucose at 5 mmol/l, the blood glucose was maintained at 5, 15 and 25 mmol/l and maintained for one hour at each level in six male patients with insulin-dependent diabetes. Insulin was infused at 0.25 mu/kg/min. Venous blood samples were taken at the beginning and end of each hour after the run-in period for assays of factor VIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), ristocetin co-factor (FVIIIR:Co), activated partial thromboplastin time (APTT) and vasopressin (aVP). There was a slight, though statistically insignificant fall in median factor VIII:C concentration at each incremental level of increase in blood glucose. Values (at the beginning and end of each hour) were: 1.0 and 1.1 iu/ml at 5 mmol/l; 0.95 and 0.79 iu/ml at 15 mmol/l; and 0.74 and 0.84 iu/ml at 25 mmol. vWF:Ag and FVIIIR:Co were unchanged. Plasma aVP fell slightly from 1.1 to 0.5 pg/ml. The results indicate that high levels of FVIII seen in diabetes are not due to short-term increases in blood glucose and that acute hyperglycaemia does not promote pro-coagulant changes in blood.
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PMID:Effect of controlled hyperglycaemia on factor VIII concentrations in insulin dependent diabetes mellitus. 313 35

Von Willebrand factor (VIII: vWf) is a glycoprotein which is essential for normal platelet adhesion to vascular subendothelium, particularly at the high shear rates encountered in small blood vessels. VIII: vWf is distributed in plasma, platelets and subendothelium, though the contributions of each pool to normal hemostasis is unknown. Raised plasma of VIII: vWf have been frequently described in association with diabetes, the highest concentrations being found in patients with retinopathy. In addition, concentrations of VIII: vWf appear to be influenced by the degree of metabolic control of the diabetics, particularly high levels being found during diabetic coma. Plasmatic concentrations of VIII: vWf greater than normal have not been shown to result in increased platelet adhesion or aggregation, so that is seems unlikely that the high levels of plasmatic VIII: vWf contribute directly to the pathogensis of retinopathy. On the other hand, increases in VIII: vWF during episodes of poor metabolic control could be evidence of reversible injury to the vascular endothelium, whereas stable, high concentrations may indicate the presence of microangiopathy.
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PMID:Von Willebrand factor, diabetes mellitus and retinopathy. 679 13

Cerebrovascular disease is one of the major causes of morbidity and mortality in the developed world. A number of important risk factors have been identified with the occurrence of stroke, including advancing age, hypertension, smoking and diabetes mellitus, but the mechanisms that link these risk factors to the development of cerebrovascular disease are unclear. The pathogenesis of cerebrovascular disease includes syndromes of atherothrombotic brain infarction and intracerebral hemorrhage. The role of abnormalities of the coagulation and fibrinolytic systems in these processes has not been properly evaluated with regard to clinical outcome, although there is evidence that raised concentrations of fibrinogen are associated with an increased risk of stroke. Smaller studies have identified increases in FVIII/vWF in association with acute stroke and raised levels of tissue plasminogen activator. Although factor VII is considered a risk factor for coronary artery disease, little is known regarding its role in the development of cerebrovascular disease. Improved understanding of the pathogenesis of stroke and the potential to predict patients at risk of stroke should herald the beginning of new approaches in stroke management.
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PMID:Risk factors for cerebrovascular disease and the role of coagulation and fibrinolysis. 757 90

Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors--fibrinogen, factor VII, factor (vWF), protein C, and antithrombin III--in four population-based samples totaling over 15,000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 microgram/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross-sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors.
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PMID:Associations of fish intake and dietary n-3 polyunsaturated fatty acids with a hypocoagulable profile. The Atherosclerosis Risk in Communities (ARIC) Study. 834 95

The effect of exercise on plasma coagulant activity was studied in 16 subjects with newly-diagnosed type II diabetes without vascular complications and 9 healthy volunteers. Generation of thrombin was determined by a computer-assisted chromogenic method and results expressed as time to generate 50% maximal thrombin activity (T50/s). In addition, APTT, factor VIII and thrombin-antithrombin III (TAT) complex levels were measured. Pre-exercise FVIII:C [mean (+/- SD)] was increased in diabetic compared to control subjects [1.5 (0.4); 0.9 (0.2) IU ml-1; (p < 0.001) respectively]. No significant differences in APTT, TAT or T50 were detected between the groups. Exercise induced a rise in FVIII complex, reduction of APTT [33 (2) s to 31 (2) s; (p = 0.004)] and T50 [58 (6) s to 53 (6) s; (p = 0.01)] in controls and an increase in FVIII complex but no significant changes in APTT or T50 in diabetic patients, with no change in TAT in either group. A greater increase in FVIII:C than vWF levels occurred in controls [0.2 (0.1); 0.1 (0.1) IU ml-1; (p = 0.005)] and patients [0.3 (0.4); 0.2 (0.1) IU ml-1; (p = 0.032)]. In patients, FVIII:C correlated inversely with APTT (r = -0.522, p = 0.038) and T50 (r = -0.592, p = 0.016). The results show that FVIII:C levels are increased at diagnosis in patients with type II diabetes without vascular disease but there is no enhancement of plasma procoagulant activity. In healthy individuals, exercise induced activation of coagulation which was not seen in patients, suggesting that it does not precipitate a state of accelerated thrombogenesis in subjects with uncomplicated type II diabetes.
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PMID:The effect of short-term exercise on plasma procoagulant activity in patients with type II (non-insulin-dependent) diabetes and healthy volunteers. 836 78

The aim of the present study was to test if long-term mortality could be predicted by endothelial derived haemostatic variables in a population with high morbidity due to thromboembolic disease. Plasma samples were drawn from 212 out-patients treated with oral anticoagulants, at the beginning of the study, and analyzed for mass concentration of tissue plasminogen activator (tPA) and its inhibitor (PAI-1), and von Willebrand factor. In the course of 3.8-year follow-up 45 patients died, including 38 vascular deaths. We found that all-cause mortality was significantly associated with increased levels of vWF and tPA. For vascular mortality there was a significant association with all three haemostatic variables (tPA, PAI-1, vWF). For vWF there was a 3-fold increase in total and vascular mortality in the highest quartile compared to the lowest quartile. There were 27 vascular deaths in the group of patients with a tPA-value above the median compared to 11 in those with a tPA below the median. In multivariate Cox regression analysis (including: age, sex, smoking habits, body mass index, diabetes mellitus, hypertension, tPA, PAI-1, and vWF), vWF and smoking were independently significantly associated with all-cause mortality, and tPA and age with vascular mortality. Endothelial derived haemostatic variables are predictors of total and vascular mortality in patients treated with oral anticoagulants.
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PMID:Endothelial haemostatic factors may be associated with mortality in patients on long-term anticoagulant treatment. 858 93

Tissue-type plasminogen activator (tPA) is an endothelium-derived vasoactive substance which is released to the blood stream by exercise, blood occlusion, and desmopressin (DDAVP). The increased capacity of the plasma tPA level raised by these factors is thought to reflect in vivo endothelial function. On the other hand, endothelial dysfunction has been reported in patients with hypercholesteremia as well as in those with diabetes mellitus. Therefore, diabetic patients with hypercholesteremia were administered 5 mg of simvastatin daily for one month and plasma tPA responses evoked by DDAVP were examined before and after treatment for hypercholesteremia. While the treatment of simvastatin for one month significantly reduced serum cholesterol levels from 257 +/- 12 mg to 206 +/- 10 mg (no change in HbA1c was observed during the study), plasma tPA levels and % delta vWF (von Willebrand factor) following DDAVP infusion significantly increased from 11.4 +/- 1.2 ng/ml to 13.4 +/- 1.4 ng/ml and from 69.3 +/- 23.4% to 126.5 +/- 47.4%, respectively. However, neither increase in plasma levels of guanosine 3', 5'-cyclic monophosphate (cGMP) nor change in the depressive response of blood pressure was observed following DDAVP infusion after the treatment of simvastatin. In addition, no change in urinary albumin excretion rate was observed with the treatment of hypercholesteremia. Therefore, it was suggested that improvement in hypercholesteremia may ameliorate vascular endothelial dysfunction in diabetic patients with hypercholesteremia and that hypercholesteremia may enhance endothelial dysfunction in these patients.
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PMID:[Effect of hypercholesteremia on vascular endothelial function and albumin excretion rate in patients with diabetes mellitus]. 895 5


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