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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients was the only independent predictor of E-selectin (P = 0.007), ICAM-1 (P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m2 or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A1c was significantly lower in IC vs. UC (IC, 8.02 +/- 0.25%; UC, 10.23 +/- 0.23%; P < 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis. Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.
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PMID:The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes. 1170 27

Several studies have shown that humoral markers of inflammation and endothelial dysfunction are predictive of macrovascular events, and correlated with indirect measures of adiposity and insulin action, thus providing a possible link between obesity, insulin resistance and atherosclerosis. We examined the relationship between humoral markers of inflammation and endothelial dysfunction and direct measures of adiposity and insulin action in Pima Indians, a population with a very high prevalence of obesity and insulin resistance, but a relatively low propensity for atherosclerotic disease. Fasting plasma concentrations of the inflammatory markers C-reactive protein (CRP), secretory phospholipase A2 (sPLA2) and soluble intercellular adhesion molecule-1 (sICAM-1) and of the endothelial markers E-selectin and von Willebrand factor (vWF) were measured in 32 non-diabetic Pima Indians (18 M/14 F, age 27+/-1 years) in whom percent body fat and insulin-stimulated glucose disposal (M) were assessed by DEXA and a hyperinsulinemic clamp, respectively. CRP, sPLA2, and sICAM-1 were all positively correlated with percent body fat (r=0.71, 0.57, and 0.51, all P<0.01). E-selectin and vWF were not correlated with percent body fat, but were negatively correlated with M (r= -0.65 and -0.46, both P<0.001) and positively correlated with CRP (r=0.46, and 0.33, both P<0.05). These findings indicate that humoral markers of inflammation increase with increasing adiposity in Pima Indians whereas humoral markers of endothelial dysfunction increase primarily in proportion to the degree of insulin resistance and inflammation. Thus, obesity and insulin resistance appear to be associated with low-grade inflammation and endothelial dysfunction, respectively, even in an obesity- and diabetes-prone population with relatively low propensity for atherosclerosis.
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PMID:Humoral markers of inflammation and endothelial dysfunction in relation to adiposity and in vivo insulin action in Pima Indians. 1188 37

The Leningrad Siege Study investigated the relationship between decreased maternal food intake and risk factors for coronary heart disease in adult life. The study screened 169 subjects exposed to intrauterine starvation during the Siege of Leningrad (now St. Petersburg) 1941-4, 192 subjects born in Leningrad before the siege and 188 subjects born concurrently with these two groups but outside the area of the siege. No difference was found between the subjects exposed to starvation in utero and during infancy in glucose tolerance [in utero: 5.2 mmol/l (95% confidence interval 5.1 to 5.3; infancy: 5.3 (5.1 to 5.5), p = 0.94], insulin concentration, blood pressure, lipid concentration or coagulation factors. The intrauterine exposed group had evidence of endothelial dysfunction by higher concentrations of von Willebrand factor and a stronger interaction between adult obesity and blood pressure. Non-systematic differences in subscapular to triceps skinfold ratio, diastolic blood pressure and clotting factors were demonstrated compared to the non-exposed groups. In conclusion, this study did not find an association between intrauterine starvation and glucose intolerance, dyslipidaemia, hypertension or cardiovascular disease in adult life. These findings differ from studies of subjects exposed to maternal starvation during the Dutch Hunger Winter. However, the dissimilar effects of exposure to the two famines may contribute to our understanding of the mechanisms of the thrifty phenotype and support the importance of catch-up growth during early childhood, a situation that occurred in the Netherlands by not in Leningrad.
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PMID:Fetal programming and the Leningrad Siege study. 1191 63

Obese patients are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the haemostatic and fibrinolytic systems. Indeed, obese subjects tend to have higher values of fibrinogen, factor VII, factor VIII, von Willebrand factor and plasminogen activator inhibitor compared to non-obese subjects. Abdominal obesity, in particular, has been shown to be associated with disturbances in fibrinogen, factor VIII and von Willebrand factor, while less consistent results have been found for factor VII. Recently it has been demonstrated that the adipocyte itself is able to produce plasminogen activator inhibitor-1, possibly explaining the high levels found in obesity. Different studies have investigated the association between haemostatic and fibrinolytic parameters and the insulin resistance syndrome, often present in obese subjects. Fibrinogen has been found to be related to insulin, but it has been suggested that this relationship is not independent of the accompanying inflammatory reaction. Results from studies on the relationship between insulin resistance and factor VII, factor VIII and von Willebrand factor levels are inconsistent. In contrast, plasminogen activator inhibitor-1 has been found to correlate with all components of the insulin resistance syndrome, and can be considered as a true component of this metabolic syndrome. Weight loss seems to have a beneficial effect on factor VII--probably mediated through a reduction in triglycerides. Data on factor VIII and von Willebrand factor are scarce but weight loss does not seem to have an effect. Fibrinogen does not seem to be reduced by modest weight loss and a more substantial weight loss seems necessary to lower fibrinogen levels. In contrast, both modest and substantial weight loss have been found to significantly reduce plasminogen activator inhibitor-1 levels. In conclusion, the increased cardiovascular risk observed in obesity could in part be explained by the association between insulin resistance and components of the fibrinolytic and haemostatic systems. Whether this relationship is truly causal or indirect needs to be elucidated further.
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PMID:Obesity, haemostasis and the fibrinolytic system. 1212 Apr 24

A leading theory of the pathophysiology of preeclampsia is that oxidative stress induces vascular endothelial cell dysfunction. Advanced glycation end products (AGEs) form when aldose sugars react nonenzymatically with proteins under conditions of oxidative stress. AGEs are circulating molecules and can generate reactive oxygen species and vascular dysfunction (in diabetes and atherosclerosis) through an association with cell surface receptors (RAGE). RAGE is a multiligand receptor, expressed in vascular tissue, which is upregulated by its own ligands. Insulin resistance and obesity are risk factors for developing preeclampsia, as well as being conditions that would increase RAGE levels. Thus, we hypothesized that women with preeclampsia will have elevated levels of RAGE protein compared with normal pregnant women. Biopsies of nonlaboring myometrium as well as omentum were taken from normal pregnant and preeclamptic women. Nonpregnant samples were obtained at the time of hysterectomy. Tissue sections were immunostained with anti-RAGE as well as anti-alpha-actin and anti-von Willebrand factor (to identify blood vessels and intact endothelial cells). Staining intensity was qualitatively described as well as given an intensity score, with the identity of the section concealed. Nonpregnant myometrial and omental vessels showed very low to undetectable levels of RAGE staining. Pregnancy induced a significant increase in RAGE protein levels in both myometrium and omental vasculature. Blood vessels from women with preeclampsia consistently had intense staining for RAGE in both vessel beds. Thus, our data suggest that since RAGE activation can induce similar pathophysiologic changes to those observed in women with preeclampsia (including NFkappaB activation, increased TNFalpha and endothelin), elevated RAGE protein may be contributing to the vascular dysfunction in preeclampsia.
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PMID:The receptor for advanced glycation end products (RAGE) is elevated in women with preeclampsia. 1290 2

Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p>0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.
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PMID:Association between obesity and a prothrombotic state: the Framingham Offspring Study. 1504 28

Disturbances of lipids metabolism described in obese persons are important factor damaging vascular endothelium. Known markers of endothelium impairment are: von Willebrand factor (vWf), tissue plasminogen activator (t-PA:Ag) and thrombomodulin (TM). The aim of the work was to evaluate markers of the endothelial disturbance in the blood plasma of persons with obesity. The study was performed in the group of 50 obese persons (39 W, 11 M) aged 35-65 (means 48.8) years with abdominal obesity. The control group consisted of 30 healthy volunteers aged 25-56 (means 41.0) years. In the poor platelet plasma obtained from venous citric blood concentrations of TM, von Willebrand factor antigen (vWf:Ag) and tissue plasminogen activator antigen (t-PA:Ag) were determined using immunoenzyme-linked assay (ELISA). In the obese persons significantly higher concentration of vWf:Ag and t-PA:Ag in comparison to control group. Analysis of results obtained according sex showed that in the blood plasma of obese women TM concentration was significantly higher than in healthy women. Our study proved that in the blood plasma of obese men there are evidences of impairment of endothelial function as higher concentration of vWf:Ag and t-PA:Ag, but in the group of obese women as the increased TM concentration.
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PMID:[Thrombomodulin, von Willebrand factor and tissue plasminogen activator in the blood plasma of obese women and men]. 1505 51

It has been suggested that elevated leptin levels underlie the low grade proinflammatory state in human obesity. We reasoned that if elevated leptin levels are an important factor in the proinflammatory state in obesity, then exogenous leptin administration during weight loss should counteract the concurrent beneficial effects of weight loss on the proinflammatory state. We therefore determined whether long-acting pegylated recombinant leptin (PEG-OB) prevents the decrease in cellular and humoral inflammation parameters during a very low calorie diet in healthy overweight young men. Except for B cells, PEG-OB treatment did not influence the decline in total leukocyte count and mononuclear subfractions during the diet. Weight loss decreased the humoral inflammation parameters TNFalpha, tissue plasminogen activator, and von Willebrand factor (P < 0.05), but in combination with PEG-OB treatment, a significant decrease was shown for inflammation markers as a whole (P < 0.014) and that of the individual parameters tissue plasminogen activator, von Willebrand factor, plasminogen activator inhibitor type 1, and intercellular adhesion molecule-1 (P < 0.05). The increase in C-reactive protein levels (P < 0.05) was the sole indication for a humoral proinflammatory action of leptin. Although PEG-OB treatment significantly increased weight loss (P < 0.03), the data do not support a proinflammatory role of leptin in human obesity.
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PMID:Leptin and the proinflammatory state associated with human obesity. 1507 Sep 44

Metabolic alterations such as insulin resistance are thought to underlie the endothelial dysfunction and low grade inflammation found in morbid obesity. Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked increment in the insulin sensitivity index (S(I)) and the endothelium-dependent vasodilatory response in a dorsal hand vein was observed after weight loss following bariatric surgery. Circulating levels of E-selectin, P-selectin, plasminogen activator inhibitor-1, and von Willebrand factor, which were higher than those in the control group, decreased significantly after surgery. Plasma vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did not change after weight loss. All inflammatory markers were higher in morbidly obese patients. After surgery, C- reactive protein and sialic acid diminished, whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not. Positive correlations were found between changes in adiposity and S(I) and changes in C-reactive protein and between changes in sialic acid and changes in endothelial function. In conclusion, a marked improvement in S(I), endothelial function, and low grade inflammation was observed in the weight-losing, morbidly obese patients after bariatric surgery. S(I) and adiposity appear to play roles in obesity-related, low grade inflammation that contribute to the endothelial dysfunction observed in morbid obesity.
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PMID:Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. 1550 18

An increased amount of deep abdominal visceral fat has generally been accepted as an important cardiovascular risk factor, and disturbances in hemostasis and fibrinolysis have been suggested to play a role. Fibrinogen and von Willebrand factor, representatives of the hemostatic system, and plasminogen activator inhibitor 1 (PAI-1), as the most important inhibitor of the fibrinolytic system, have been associated with visceral obesity, with the most convincing evidence found for the involvement of PAI-1. The association with fibrinogen and von Willebrand factor has been suggested to be merely a reflection of the association with inflammation and endothelial dysfunction. The fact that PAI-1 is secreted by adipose tissue has attracted much attention. The increase of PAI-1 in visceral obesity could be because visceral adipose tissue produces more PAI-1 compared with subcutaneous abdominal adipose tissue. The contribution of other cell types such as hepatocytes or endothelial cells is probably more important, with stimulation of PAI-1 production by different components of the metabolic syndrome. PAI-1 secretion by adipose tissue has been suggested to have a more local effect, playing a role in tissue remodeling during the development of obesity.
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PMID:Visceral fat as a determinant of fibrinolysis and hemostasis. 1596 80


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