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Query: UMLS:C0011849 (diabetes)
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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

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
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PMID:Endothelial function and hemostasis. 1079 71

To critically evaluate the relative importance of coagulation abnormalities over other clinical variables for micro- and macrovascular diabetic complications, prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), fibrin degradation product d-dimer, and alpha2 plasmin inhibitor complex were determined in 101 stable, relatively well controlled patients with Type 2 diabetes (the mean HbA1c, age and duration of diabetes, 7.1%, 61 and 7.5 years, respectively). First, incidence and severity of diabetic micro- and macroangiopathies were progressively increased with the severity of coagulation abnormalities. Next, correlation of the four values with the presence of micro- and macrovascular complications, respectively, was analyzed by the multiple logistic regression analysis, with the inclusion of other variables such as age, duration of diabetes, HbA1c, blood pressure, and urinary albumin excretion. With the presence of microangiopathies, F1+2 and systolic blood pressure were significantly related, with the relationship being very strong for the former (P=0.003) and weak for the latter (P=0.035). On the other hand, with the presence of macroangiopathies, F1+2 (P=0.003), TAT (P=0.002), duration of diabetes (P=0.015), and age (P=0.013) were related. Other clinical variables were not significantly related with the presence of complications. Coagulation and fibrinolytic abnormalities are stronger determinants of the presence of diabetic vascular complications than other clinical variables including the degree of glycemia, in stable, relatively well controlled patients with Type 2 diabetes.
Diabetes Res Clin Pract 2000 Jul
PMID:Importance of hypercoagulability over hyperglycemia for vascular complication in type 2 diabetes. 1080 60

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

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.
J Diabetes Complications
PMID:Elevation of fibrinogen and thrombin-antithrombin III complex levels of type 2 diabetes mellitus patients with retinopathy and nephropathy. 1098 19

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.
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PMID:Activated protein C resistance is a risk factor for central retinal vein occlusion. 1105 59

Although macroangiopathies such as peripheral vascular disease (PVD), cerebral vascular disease (CVD), and coronary heart disease (CHD) can often be observed in patients with diabetes mellitus, they are not specific for diabetes mellitus. Moreover, it is unclear whether their progressive mechanism is different. In the present study, we compared the risk factors among the diabetic macrovascular complications. Univariate analyses showed that in all patients, age at examination, duration of diabetes, thrombin-antithrombin III complex (TAT) level, fibrinogen level, lipoprotein (a) (Lp(a)) level, total cholesterol (T-Chol) level, and existence of microagiopathy were risk factors for PVD. Age, duration of diabetes, insulin level, TAT level, fibrinogen level, HDL cholesterol (HDL-Chol) level, hypertension, and nephropathy were risk factors for CVD. Only fibrinogen level was a risk factor for CHD. Moreover, Lp(a) level was a risk factor for PVD and CVD in male patients, but not in females. On the other hand, insulin level was a risk factor for CVD in female patients, but not in males. Multivariate analyses showed that TAT level, T-Chol level, and neuropathy were independent variables for PVD and that age, TAT level, and HDL-Chol level were independent variables for CVD. On the other hand, only fibrinogen level was the independent variable for CHD in males. Our results suggest that the progressive mechanism of PVD and CVD might be different from that of CHD and might differ according to gender in Japanese diabetic patients.
J Diabetes Complications
PMID:Comparison of risk factors of macrovascular complications. Peripheral vascular disease, cerebral vascular disease, and coronary heart disease in Japanese type 2 diabetes mellitus patients. 1112 Apr 54

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.
Diabetes Res Clin Pract 2002 Feb
PMID:Relationship of abdominal fat with metabolic disorders in diabetes mellitus patients. 1179 80

To evaluate the association between haemostatic parameters and increased risk of myocardial infarction (MI) at a young age, we measured fibrinogen, factor VII, antithrombin III, protein C, protein S, tissue factor (TF), free form tissue factor pathway inhibitor (TFPI), plasminogen, alpha2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor-I (PAI-I), and lipoprotein (a) in 140 young men with MI before age 45 and 150 age-matched healthy men. TF, TF/TFPI ratio, PAI-I, PAI-I/tPA ratio, plasminogen, and lipoprotein (a) in young MI patients were all significantly higher than controls, while TFPI, antithrombin II, and tPA were significantly lower (P <0.001 of each). Significant determinants of MI risk were PAI-I/tPA ratio (R2 = 0.300, P <0.001), TF/TFPI ratio (R2 = 0.049, P <0.001), antithrombin III (R2 = 0.034, P <0.001), hyperlipidaemia (R2 = 0.019, P = 0.004), diabetes (R2 = 0.014, P = 0.015), lipoprotein (a) (R2 = 0.012, P = 0.023), alpha2-antiplasmin (R2= 0.014, P = 0.012), and protein C (R2= 0.012, P = 0.018). We conclude that the imbalances of PAI-I/tPA and TF/TFPI are significantly associated with MI at a young age, perhaps mediated via impaired fibrinolytic activity.
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PMID:Imbalance of plasminogen activator inhibitor-I/ tissue plasminogen activator and tissue factor/tissue factor pathway inhibitor in young Japanese men with myocardial infarction. 1181 7


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