Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. 762 4

Microalbuminuria, i.e., slightly elevated urinary albumin excretion rate (UAER), notifies increased risk for atherosclerotic disease and may reflect an early generalized vascular abnormality in healthy subjects. This study was designed in order to examine whether such abnormality is associated with a shift of the haemostatic balance in prothrombotic direction. The following haemostatic factors were measured in two representative groups of clinically healthy subjects, 28 with microalbuminuria (UAER of 6.6-150 micrograms/min) and 60 age- and sex-matched controls with normoalbuminuria (UAER < 6.6 micrograms/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors: plasma concentrations of tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 antigen; and endothelial factor: plasma von Willebrand factor antigen concentration. The fibrinolytic and endothelial factors were measured both before and after 10 minutes of venous occlusion of the arm. None of the haemostatic factors were significantly altered in the microalbuminuric group. Plasma fibrinogen concentration tended to be elevated but not statistically significant ((mean (95% C.I.) 7.8 (7.2-8.3) vs. 7.2 (6.9-7.5) mumol/l; p < 0.1). Neither did any of the haemostatic factors correlate with UAER in regression analyses. It is concluded that the haemostatic balance is unaltered in healthy subjects with microalbuminuria. It is unlikely that a prothrombotic state is present as an intermedial factor early in a causal chain between microalbuminuria and atherosclerotic vascular disease.
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PMID:Aspects of haemostatic function in healthy subjects with microalbuminuria--a potential atherosclerotic risk factor. 777 57

Microalbuminuria is an important risk factor for cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) patients although the pathogenic mechanism between microalbuminuria and cardiovascular disease has not yet been established. Microalbuminuria in insulin-dependent diabetes mellitus (IDDM) patients has been related to abnormalities in haemostasis, poor glycaemic control, disadvantageous alterations in the lipid spectrum and elevated concentrations of lipoprotein(a), another independent risk factor for cardiovascular disease. In this study the interrelations between microalbuminuria and metabolic control, lipoprotein(a), other blood lipids and several haemostasis parameters were studied in 96 NIDDM patients (50 women, 46 men). Forty-three patients showed microalbuminuria. No significant differences were found in blood lipids (Lp(a), serum cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides), glycaemic control (HbA1c) and several haemostasis parameters (factor VII, VIII, fibrin monomer, thrombin-antithrombin III, D-dimer, tissue plasminogen activator antigen and plasminogen activator inhibitor-1) between the micro- and normoalbuminuric subgroups. In the microalbuminuric subgroup increased concentrations for plasminogen and alpha 2-antiplasmin were measured. In general, the presence of microalbuminuria was not associated with significant alterations in glycaemic control, blood lipids or haemostasis parameters in this group of 96 NIDDM patients. Further investigation is required to explain the excess cardiovascular mortality in patients with an elevated urinary albumin excretion rate.
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PMID:The effect of microalbuminuria on glycaemic control, serum lipids and haemostasis parameters in non-insulin-dependent diabetes mellitus. 825 Apr 95

Increased urinary albumin loss in patients with Type 1 diabetes is associated with accelerated atherosclerosis. Prothrombotic factors known to be associated with cerebrovascular and coronary artery disease in the general population, antithrombotic factors, were studied in 52 patients with Type 1 diabetes and varying urinary albumin loss and 24 non-diabetic control subjects. Fibrinogen increased from 2.5 g l-1 (95% confidence interval 2.3-2.8) in control subjects and 2.8 g l-1 (2.6-3.0) in diabetic patients without microalbuminuria to 3.1 g l-1 (2.7-3.5) with microalbuminuria (p < 0.005 vs control; p < 0.001 vs without microalbuminuria). Factor VIIc increased from 81% (75-86% in non-diabetic control subjects and 84% (78-90%) in diabetic patients without microalbuminuria to 103% (89-117%) with microalbuminuria (p < 0.005 vs control; p < 0.05 vs without microalbuminuria) and 118% (86-150%) with albuminuria (p < 0.005 vs control and p < 0.001 vs without microalbuminuria). Levels of the antithrombotic factors protein C, protein S, and antithrombin III also rose in the diabetic patients with evidence of renal damage. Elevation of prothrombotic factors has been associated with increased risk of microvascular disease, whereas elevation of antithrombotic factors has no known protective effect. Therefore, this pattern of alteration of haemostatic factors in diabetic renal disease may contribute to the increased risk of vascular disease associated with both microalbuminuria and albuminuria.
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PMID:Prothrombotic and antithrombotic factors are elevated in patients with type 1 diabetes complicated by microalbuminuria. 845 88

Microalbuminuria and haemostasis derangements have been considered as independent risk factors for cardiovascular death in type 2 (non-insulin-dependent) diabetic patients. Few studies have assessed coagulation inhibitors in type 2 diabetic patients with normoalbuminuria and microalbuminuria. Therefore, 32 type 2 diabetic patients with normoalbuminuria (albumin excretion rate, AER < 20 mg/min, mean 7 +/- 1) and 28 type 2 diabetic patients with microalbuminuria (AER 20-200 mg/min, mean 84 +/- 11) were studied. The patients were matched for age, sex, disease duration and treatment, body mass index (BMI), blood pressure and glycohaemoglobin. Protein C and S activity, antithrombin III, thrombomodulin and prothrombin fragments 1 + 2 (F 1 + 2) were assessed together with fibrinogen, triglycerides, total and high density lipoprotein (HDL)-cholesterol concentrations. Fibrinogen, total and low density lipoprotein (LDL) concentrations were similar in the two groups, while a significant difference was observed for triglycerides (normoalbuminuric group: 128 +/- 10 mg/dl, microalbuminuric group: 184.1 +/- 17 mg/dl; P < 0.007) and HDL-cholesterol (normoalbuminuric group: 45 +/- 2 mg/dl, microalbuminuric group: 39 +/- 2 mg/dl; P < 0.05). The coagulation parameters were as follows: normoalbuminuric group: protein C activity 109% +/- 5%, protein S 95.4% +/- 5%, thrombomodulin 49.3 +/- 3 ng/ml, antithrombin III 93.3% +/- 3%, F 1 + 2 1.05 +/- 0.04 nmol/l; microalbuminuric group: protein C activity 107% +/- 4%, protein S 98.4% +/- 4%, thrombomodulin 64.4 +/- 4 ng/ml, antithrombin III 93.3% +/- 3%, F 1 + 2 1.03 +/- 0.05 nmol/l. The difference was significant for thrombomodulin (P < 0.007). A significant direct correlation was observed in the microalbuminuric group between AER and thrombomodulin (r = 0.38, P < 0.05). In conclusion, our data do not support the hypothesis that a reduction in the activity of anticoagulant physiological inhibitors (protein C, protein S, antithrombin III) could contribute to explain the higher cardiovascular risk in type 2 diabetic patients with microalbuminuria. The elevation of plasma thrombomodulin concentration in type 2 diabetic patients could be the consequence of widespread vascular damage in diabetic patients with incipient nephropathy.
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PMID:Physiological inhibitors of blood coagulation and prothrombin fragment F 1 + 2 in type 2 diabetic patients with normoalbuminuria and incipient nephropathy. 890 33

Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin-dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirteen patients presented clinically detectable microangiopathy (8 retinopathy and 5 both retinopathy and microalbuminuria). A cross-sectional study of lipid profile, coagulation parameters, and a flow-cytometric evaluation of tissue factor expression in normal monocytes induced by patient plasma were performed. Patients were re-evaluated for microangiopathy in a 3-year median follow-up. Patients showed triglyceride enrichment in low (P = 0.00002) and high density lipoproteins (P = 0.004) and increased levels of D-dimer (P < 0.00001), prothrombin fragment 1 + 2 (P < 0.00001), and thrombin-antithrombin III complex (P = 0.0001). Patients with clinically detectable microangiopathy had increased type 1 plasminogen activator inhibitor (P = 0.00001), thrombomodulin (P = 0.02), and induced monocyte tissue factor expression (P < 0.00001). Nine patients developed clinically detectable microangiopathy in the follow-up and the only predictive variable was increased induced tissue factor expression. In conclusion, in these patients elevated thrombin and fibrin generation reflects a hypercoagulable state but clinically detectable microangiopathy seems related to endothelial cell injury markers and to increased induced tissue factor expression on monocytes.
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PMID:Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: a prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus. 932 50

Diabetes is associated with a hypercoagulable state. Blood hypercoagulability may accelerate atherosclerosis and the diabetic microvascular complications. Thrombin-antithrombin III complex (TAT) and fibrinogen levels are parameters of coagulation and fibrinolysis. In the present study, we examined the risk factors for the diabetic microangiopathy including TAT and fibrinogen levels. To investigate the relationship between the clinical parameters and microangiopathy in type 2 diabetic patients, the clinical parameters of subjects with microangiopathy were compared with those of subjects without microangiopathy. The clinical parameters were as follows: age at examination, duration of diabetes, fasting plasma glucose (FPG) level, HbA(1C) level, insulin level, TAT level, fibrinogen level, lipoprotein (a) (Lp(a)) level, total cholesterol level, triglyceride level, HDL cholesterol level and existence of hypertension. The plasma TAT and fibrinogen levels were significantly higher in patients with retinopathy or nephropathy than in patients without these complications. Moreover, fibrinogen levels of patients with microalbuminuria or background retinopathy were significantly higher than those of patients with normoalbuminuria or no retinopathy. The duration of diabetes was significantly longer in patients with any microangiopathy than in patients without it. Multiple regression analyses showed that duration and fibrinogen level were independent factors associated with the existence of retinopathy or nephropathy. Our data show that the disorder of coagulation and fibrinolysis is significantly associated with diabetic retinopathy and nephropathy and exists at the early stage of microangiopathy.
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PMID:Elevation of fibrinogen and thrombin-antithrombin III complex levels of type 2 diabetes mellitus patients with retinopathy and nephropathy. 1098 19

The aim of this cross-sectional study was to investigate the relationship between low-grade albuminuria (microalbuminuria) and factors of the coagulation- and fibrinolysis systems in 104 clinically healthy 58-year-old men recruited from the general population. Urinary albumin excretion was significantly associated with body mass index, systolic and diastolic blood pressure, plasminogen activator inhibitor (PAI)-1 activity, tissue plasminogen activator (tPA) antigen, tPA activity (negatively) and protein S (P<0.05). There were no associations between urinary albumin excretion and antithrombin III, fibrinogen, protein C, thrombin/antithrombin factor or von Willebrand factor. In multiple regression analysis urinary albumin excretion was independently and significantly associated with PAI-1 activity and systolic blood pressure (P<0.05). In conclusion we report that urinary albumin excretion was independently and significantly associated with PAI-1 activity in clinically healthy 58-year-old men. This relationship may contribute to the previously reported increased cardiovascular morbidity in subjects with microalbuminuria.
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PMID:Independent relationship between microalbuminuria and plasminogen activator inhibitor-1 activity (PAI-1) activity in clinically healthy 58-year-old men. 1142 21

In this study, we examined the relationships of the fat distribution with the clinical parameters, microangiopathy, and coagulation disorders in Japanese diabetic patients, distinguishing between males and females. To investigate these relationships, the clinical parameters of the patients were compared with the total abdominal fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), BMI, and percent body fat. In addition, microangiopathies and coagulation disorders of the patients were also compared with the fat distribution. In the male patients, the insulin level, triglyceride (TG) level, and diastolic blood pressure significantly correlated with both VFA and SFA. The HDL cholesterol (HDL-Chol) level and systolic blood pressure also significantly correlated with VFA, but not with SFA. In the female patients, the insulin level, TG level, HDL-Chol level and systolic blood pressure significantly correlated with VFA. On the other hand, only the systolic and diastolic blood pressures significantly correlated with SFA. The fibrinogen and thrombin-antithrombin III complex (TAT) levels significantly correlated with VFA only in the female patients. The male patients with macroalbuminuria had significantly larger VFA than those with microalbuminuria or normoalbuminuria. However, SFA had no relation with the urinary albumin excretion rate. The multiple regression analysis showed that VFA was an independent variable associated with diabetic nephropathy in the male patients. In conclusion, VFA plays more important role than SFA in the metabolic disorders and diabetic nephropathy in the Japanese diabetic patients. In the female diabetic patients, VFA may be associated with disorders of coagulation and fibrinolysis.
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PMID:Relationship of abdominal fat with metabolic disorders in diabetes mellitus patients. 1179 80