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Query: UMLS:C0011849 (diabetes)
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Hemostatic factors play an important role in the complications of ischemic heart and vessel disease. Dietary fats such as n-3 fatty acids have been shown to possibly influence hemostatic factors. However, most studies reporting an inverse association between cardiovascular disease and fish and n-3 fatty acid consumption used supplemental doses of fish oil or intakes exceeding the typical amount consumed by the US population. This report examined the associations of usual intakes of fish, linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid with fibrinogen, factor VII, factor VIII, and von Willebrand factor in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The analyses reported here included 1672 black and white men and women aged 24 to 42 years in 1992 to 1993. After adjustment for age, body mass index, diabetes, number of cigarettes smoked per day, race, and energy and alcohol consumption, no significant associations were observed between those who consumed no fish versus those who consumed the highest level of dietary fish with respect to fibrinogen, factor VIII, or von Willebrand factor for any race-sex group. Comparisons of tertile 1 versus tertile 3 for dietary linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were also not significantly associated with fibrinogen, factor VII, factor VIII, or von Willebrand factor for any race-sex group. These data suggest that customary intakes of fish and n-3 fatty acids in populations that generally do not consume large amounts of these food items are not associated with these hemostatic factors.
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PMID:Association of dietary fish and n-3 fatty acid intake with hemostatic factors in the coronary artery risk development in young adults (CARDIA) study. 967 72

We studied the effects of genetic and environmental influences on factor VII coagulant activity (VIIc) in Chinese diabetic patients (263 with Type II [non-insulin-dependent] diabetes mellitus, 78 with Type I [insulin-dependent] diabetes mellitus) and 143 normal control subjects. VIIc was measured by a one-stage biological assay. The R/Q353 or Msp1 polymorphism at codon 353 of the factor VII gene was detected after Msp1 digestion of polymerase chain reaction-amplified genomic DNA. In both diabetic and control subjects the allele frequencies of the R (M1) and Q (M2) alleles were 0.96 and 0.04; the corresponding reported frequencies in Caucasians being 0.90 and 0.10: VIIc were 21% lower in Chinese control subjects and Type I diabetic patients with R/Q, compared with R/R subjects (p < 0.001 and p < 0.05). The corresponding difference was 4% for Type II diabetc patients (p = NS). Type II diabetic patients had higher mean VIIc levels than control subjects and Type I diabetic patients (p < 0.01); they were also older, and had higher serum creatinine and triglyceride (all p < 0.01). They also had higher VIIc levels than an age-matched older control group (p < 0.01; n = 182) in whom the genotype effect was clearly seen. On stepwise linear regression analysis, the significant independent determinants of VIIc were serum triglyceride (contributing 20% and 25% to variance in control subjects and diabetic patients), the R/Q353 genotype (contributing to 12% of the variance in control subjects but only 1% in diabetic patients), age and total cholesterol in all subjects, and in the diabetic patients female sex, urinary albumin excretion rate and serum creatinine. VIIc was higher in diabetic patients with macroangiopathy and retinopathy (both p < 0.0001). We conclude that compared with Caucasians, the Q allele frequency is significantly lower in these Chinese subjects. Plasma VIIc is determined by both genetic and environmental influences such that in Chinese Type II diabetic patients, the effect of environmental factors predominates, almost negating the influence of the R/Q353 genotype. High VIIc may contribute to the increased cardiovascular risk in Type II diabetic patients.
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PMID:Genetic influence of the R/Q353 genotype on factor VII activity is overwhelmed by environmental factors in Chinese patients with Type II (non-insulin-dependent) diabetes mellitus. 968 15

The contribution of coagulation factors and fibrinolytic variables to the development of ischaemic arterial disease is still not clearly established. The PRIME study is a prospective cohort study of myocardial infarction in men aged 50-59 years and recruited from three MONICA field centers in France (Lille, Strasbourg and Toulouse) and the center in Northern Ireland (Belfast). Baseline examination included measurement of plasma fibrinogen, factor VII, and PAI-1 activity in over 10,500 participants. We investigated the associations of these haemostatic variables with cardiovascular risk factors, prevalent atherosclerotic disease and geographical area. Fibrinogen level increased with age, smoking, waist-to-hip ratio, LDL-cholesterol, and it decreased with educational level, leisure physical activity, alcohol intake and HDL-cholesterol. Factor VII activity increased with body mass index, waist-to-hip ratio, triglycerides. HDL- and LDL-cholesterol. PAI-1 activity increased with body mass index, waist-to-hip ratio, triglycerides, alcohol intake, smoking, and decreased with leisure physical activity. PAI-1 level was higher in diabetic subjects than in subjects without diabetes. Cardiovascular risk factors explained 8%, 9%, and 26% of the total variance in fibrinogen, factor VII, and PAI-1, respectively. Compared with participants without prevalent cardiovascular disease, those with previous myocardial infarction (n = 280), angina pectoris (n = 230), or peripheral vascular disease (n = 19) had significantly higher levels of fibrinogen. but those with stroke (n = 67) had not. PAI-1 activity showed a similar pattern of association. The odds ratio for cardiovascular disease associated with a rise of a one standard deviation in fibrinogen and PAI-1 was 1.31 (95% confidence interval: 1.20 to 1.42, p <0.001) and 1.38 (95% confidence interval: 1.27 to 1.49, p<0.001), respectively. After adjustment for cardiovascular risk factors, these associations were attenuated but remained highly significant. There was no significant association between factor VII activity and prevalent cardiovascular disease. Fibrinogen level and, to a lesser extent, factor VII and PAI-1 activity were higher in Northern Ireland than France after adjustment for the main cardiovascular risk factors. These geographical variations are consistent with the 2 to 3-fold higher incidence of myocardial infarction in Northern Ireland than France. Our results provide further epidemiological evidence for a possible role of fibrinogen and PAI-1 in the pathogenesis of coronary heart disease.
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PMID:Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction--the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. 984 66

Patients with diabetes have an increased prevalence of premature atherosclerotic vascular disease, and alterations in plasma coagulation proteins have been incriminated as a possible cause. The roles of hyperglycemia and hyperinsulinemia in the pathogenesis of these changes are unknown. To examine the effects of prolonged hyperglycemia and of selective hyperinsulinemia on the tissue factor pathway of blood coagulation, nine healthy young men were infused with glucose to maintain levels at 11.1 mmol/l (approximately 200 mg/dl) for 18-72 h (hyperglycemia-hyperinsulinemia group). Five normal men were infused with regular insulin to maintain levels comparable to that in the previous group (900 pmol/l, approximately 150 microU/ml) and with glucose to maintain levels at 5.6 mmol/l (approximately 100 mg/dl) (euglycemia-hyperinsulinemia group). Measured were plasma activated factor VII activity (FVIIa), FVII coagulant (FVIIC) activity, FVIII coagulant (FVIIIC) activity, tissue factor pathway inhibitor (TFPI) antigen, and thrombin markers; and serum glucose, insulin, and electrolytes. Plasma FVIIa, FVIIC, FVIIIC, and TFPI rose during hyperglycemic-hyperinsulinemia but not during euglycemic-hyperinsulinemia. Markers of thrombin generation rose transiently and inconsistently during hyperglycemia-hyperinsulinemia. We concluded that in normal subjects, hyperglycemia-hyperinsulinemia induced activation of the tissue factor pathway, reflected by increases in plasma FVIIa, FVIIC, and TFPI. This activation was independent of hyperinsulinemia, hypertriglyceridemia, and hyperosmolality. The elevations in plasma coagulation factors during hyperglycemia-hyperinsulinemia, characteristic of type 2 diabetes, may constitute a potential for enhanced thrombin generation and thrombosis when triggered by exposure of tissue factor, such as during arterial plaque rupture.
Diabetes 1999 May
PMID:Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men. 1033 23

A slightly elevated urinary albumin excretion rate (UAER), above 5-10 microgram/min, is a predictor of atherosclerotic cardiovascular disease. Endothelial dysfunction is an important early feature of atherosclerosis. The plasma concentration of von Willebrand factor (vWF), a potential marker of endothelial dysfunction, predicts a subsequent increase of UAER in patients with diabetes. The aim of this study is to test the hypothesis that high concentrations of vWF as well as other haemostatic factors predict progression of UAER in clinically healthy subjects. UAER was measured together with selected markers of haemostatic function-vWF, tissue plasminogen activator (tPA), plasminogen activator inhibitor, factor VII and fibrinogen-in healthy volunteers aged 40-65 years. After a mean follow-up of 4.1 years, 64 of 74 agreed to a re-examination including re-measurement of UAER. Baseline vWF and tPA were both positively correlated to the change in UAER during follow-up (r=0.26, P=0.04 and r=0.40, P=0.001 respectively). The mean UAER increased significantly by 7.6 microgram/min and 7.5 microgram/min respectively in subjects with vWF and tPA above the medians at baseline (P=0.01 and P=0.003 respectively), whereas no changes in UAER were seen in subjects with vWF and tPA below the medians. Subjects with high tPA were also characterized by an excess of other cardiovascular risk factors at baseline. No significant differences in these risk factors were present between subjects with high or low vWF. High plasma concentrations of vWF and tPA are associated with progression of UAER in clinically healthy subjects. Both vWF and tPA are secreted by endothelial cells and the results suggest that endothelial dysfunction leads to progression of UAER.
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PMID:Endothelial haemostatic factors are associated with progression of urinary albumin excretion in clinically healthy subjects: a 4-year prospective study. 1036 4

Etofibrate is a hypolipemic drug belonging to the fibrate class. By improving the lipid profile, these drugs often exert a favorable influence on hemostatic risk factors of ischemic heart disease. We present a pilot study on the influence of etofibrate on lipids and lipoproteins in serum, as well as on factor VII and fibrinogen. The study group was comprised of 18 males, aged 52.5 +/- 7.3 years, with hypertriglyceridemia or mixed hyperlipoproteinemia and other risk factors of atherosclerosis, particularly insulin-dependent diabetes and arterial hypertension. The group was further divided into two subgroups depending on the coexistence of arterial hypertension. All patients received etofibrate 500 mg daily for 3 months. In comparison with initial values, a decrease in the following was noted for the whole study group: triglyceride level (226.0 +/- 27.1 vs. 288.0 +/- 51.9 mg/dl; p < 0.05), percent LDL-cholesterol (72.4 +/- 1.8 vs. 75.8 +/- 1.7; p < 0.05), apolipoprotein B (111.2 +/- 4.6 vs. 115.3 +/- 5.4 mg/dl; p < 0.05), atherogenic indices: LDL/HDL (5.06 +/- 0.58 vs. 5.95 +/- 0.50; p < 0.02) and apolipoprotein B and A (apoB/apoA) (0.92 +/- 0.04 vs. 1.02 +/- 0.06; p < 0.05). There was an increase in percent HDL-cholesterol (14.7 +/- 1.1 vs. 12.8 +/- 0.7; p < 0.05) and apoA (121.0 +/- 4.8 vs. 111.2 +/- 2.4 mg/dl; p < 0.05). A marked decrease in the level of factor VII (FVIIc) (114 +/- 5.9 vs. 136 +/- 5.3%; p < 0.001) and fibrinogen (2.95 +/- 0.17 vs. 3.58 +/- 0.17 g/l; p < 0.01) was found. Fibrinogen levels fell notably (3.09 +/- 0.30 vs. 3.87 +/- 0.34 g/l; p < 0.05) in the subgroup with arterial hypertension, and F1 + 2 markers tended to decline (2.32 +/- 0.53 vs. 2.74 +/- 0.37 nmol/l; NS). Patients with normals arterial pressure maintained their fibrinogen levels (3.23 +/- 0.24 vs. 3.36 +/- 0.26 g/l; NS). A positive correlation between FVIIc and F1 + 2 was observed during treatment. All results were expressed as arithmetic means +/- SE. The present study has demonstrated that etofibrate has hypolipemic, antithrombotic and antiatherosclerotic properties in patients with polymetabolic syndrome.
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PMID:Etofibrate decreases factor VII and fibrinogen levels in patients with polymetabolic syndrome. 1045 May 39

Diabetes mellitus is associated with vascular and neurological complications. We have investigated the presence of antibodies to phospholipids and to phospholipid binding plasma proteins in blood samples collected from 68 clinically and biochemically characterized type I and type II diabetic patients and from 252 healthy blood donor controls. Each sample was analysed for antibodies to three phospholipids (cardiolipin, phosphatidylserine and phosphatidylethanolamine), the antibody isotypes (IgA, IgG and IgM), and whether antibody activity was plasma protein-dependent. Patients were considered to have anti-phospholipid antibodies when one or more of these 18 tests was found above predetermined control values. The results of these experiments revealed an increased incidence of anti-phospholipid antibodies in diabetic patients compared with control subjects. The incidence of IgA isotype to phosphatidylethanolamine was higher than the incidence of other isotypes to other phospholipids, and their reactivities were independent of phospholipid-associated proteins. In addition, these antibody findings were studied for associations with prothrombin degradation products, activated factor VII and activated protein C, and with the incidence of diabetic complications. The anti-phosphatidylethanolamine antibody association with proliferative retinopathy was significant.
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PMID:Qualitative and quantitative studies of autoantibodies to phospholipids in diabetes mellitus. 1054 Jan 56

Atherosclerosis is more extensive and occurs earlier in diabetics compared with the general population. The pathophysiology of atherosclerosis is not fully established. We compared the activity of two blood clotting agents, activated factor VII (VIIa) and von Willebrand factor (vWF), in diabetic and non-diabetic subjects with coronary artery disease. According to clinical features, subjects were placed in one of four groups: Group I, non-insulin-dependent diabetes mellitus (NIDDM) with coronary heart disease (CAD) (n = 16); Group II, NIDDM (n = 15); Group III, CAD with no presence of diabetes (n = 17); and Group IV, healthy volunteers (n = 15). The level of factor VIIa was higher in Group I compared with all other groups, and was significantly higher in Group II compared with Group III and Group IV. Activity of vWF was higher in Group I compared with Group II, Group III and Group IV. There was no statistical difference between Group II and Group III. There was no significant correlation between concentration of blood glucose, total cholesterol or triglyceride, duration of diabetes and either factor VIIa or vWF activity. The results of this study suggest that increased activity of plasma vWF and factor VIIa may be useful markers to identify ischaemic heart disease risk in NIDDM subjects.
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PMID:Activity of factor VIIa and von Willebrand factor in non-insulin-dependent diabetic subjects with coronary artery disease. 1059 31

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

Although numerous cross-sectional studies have identified possible determinants of plasma fibrinogen and factor VII levels, few prospective studies exist. We assessed the longitudinal relation of changes in fibrinogen and factor VII over 6 years with changes to other cardiovascular risk factors in a sample of 440 men and 549 women from the Atherosclerosis Risk in Communities (ARIC) study. Fibrinogen increased more in older participants, those with or who developed diabetes, those who at any time smoked, and those whose plasma HDL cholesterol or triglycerides decreased and increased less in female participants who started hormonal replacement therapy. Factor VII coagulant activity increased more in younger participants, women, those who gained greater weight or developed diabetes, those who quit smoking, those in whom plasma triglycerides decreased, and female participants who received hormonal replacement therapy. Thus, our longitudinal data suggest with some exceptions that adverse changes in cardiovascular risk factors are accompanied by increases in plasma levels of fibrinogen and factor VII.
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PMID:Determinants of population changes in fibrinogen and factor VII over 6 years: the Atherosclerosis Risk in Communities (ARIC) Study. 1066 61


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