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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the submitted pilot study the authors examined 47 diabetic patients without vascular complications and 15 healthy blood donors. In an aged-matched sub-group the authors confirmed significantly elevated levels of Willebrand factor (vWF) in patients with non-insulin dependent diabetes mellitus (NIDDM), as compared with healthy blood donors, while the thrombomodulin (TM) levels did not differ significantly. The mutual correlation of parameters with calcium-dependent release (vWF, platelet factor PF4 and C-peptide) was confirmed in the group of patients with NIDDM with normal TM values and in the group of blood donors. These findings could be explained by the hypothesis that raised intracellular calcium levels, described already in early stages of diabetes could in diabetic patients participate also in the activation of haemostasis.
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PMID:[Hemostasis in patients with diabetes mellitus. I. Markers of endothelial dysfunction]. 897 57

Endothelial cell injury has been implicated in the increased incidence of vascular disease associated with diabetes mellitus. In diabetic humans, elevated plasma von Willebrand Factor (vWF) has been interpreted as an indication of endothelial damage. In contrast, in an animal model of inherited insulin-dependent diabetes, the bio-breeding (BB) rat, plasma vWF levels did not differ from those in age-matched control rats during the first 7 months of diabetes although morphological evidence of mild aortic endothelial alteration or injury was observed. In the present study efforts have been made to define the endothelial alterations in BB diabetic rats compared to controls more precisely over this time period. Thus, adhesion molecules: intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) were evaluated by in situ immunohistochemistry, vWF content was determined by biochemical analysis of aortic extracts and by quantitative immunohistochemistry, plasma vWF levels were measured by ELISA and vWF mRNA by RNAse protection assay. Neither age nor diabetic state significantly affected either the expression of adhesion molecules, or the levels of circulating vWF. Endothelial vWF content was significantly increased in the diabetic vessels, as observed by both approaches but the vWF mRNA content was not different from that in control vessels. Plasma plasminogen activator inhibitor (PAI-1) activity was significantly increased in diabetic animals. In conclusion, endothelial alterations in BB rats associated with diabetes, together with the raised plasma PAI-1 levels, promote the thrombogenic potential of the vessel wall, and are consistent with an increased risk for vascular disease.
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PMID:Aortic endothelial cell von Willebrand factor content, and circulating plasminogen activator inhibitor-1 are increased, but expression of endothelial leukocyte adhesion molecules is unchanged in insulin-dependent diabetic BB rats. 1072 83

It is known that either chronic glucocorticoid administration or endogenous hypercortisolism frequently induce an hypercoagulable condition. Since little is known about the evaluation of markers of haemostatic and fibrinolytic systems in other adrenal disorders, we studied plasminogen activator inhibitor (PAI-1), tissue-plasminogen activator (t-PA), fibrinogen and von Willebrand factor antigen (vWF-Ag) levels in 11 patients with Cushing's syndrome and in 12 patients with adrenal incidentaloma. In patients with Cushing's syndrome mean PAI-1, t-PA and vWF-Ag levels did not significantly differ from those found in 50 age- and sex-matched controls, while mean fibrinogen levels were significantly higher in patients (337.0+/-39.1 mg/dl) than in normal subjects (278.9+/-8.4 mg/dl). Patients with adrenal incidentaloma showed PAI-1, t-PA and vWF-Ag mean levels superimposable to those in controls, while fibrinogen (319.7+/-27.9 mg/dl) was slightly, although not significantly, higher than in normals. Considering the limits of normal values (as mean+/-2 SD) obtained in the control group, high PAI-1 levels were found in 2 patients with Cushing's syndrome and in 3 patients with incidentaloma. An elevation of fibrinogen levels was found in 3 patients with Cushing's syndrome and in 3 with incidentaloma. Increased vWF-Ag levels were found only in 1 patient with Cushing's syndrome. An increased t-PA level was occasionally observed only in the patient with adrenal carcinoma. On the whole, an alteration of at least one of haemostatic and fibrinolytic parameters was detected in 55% of the patients with Cushing's syndrome and in 42% of those with adrenal incidentaloma. In conclusion, early alterations of coagulation and fibrinolytic systems may be found in some patients with adrenal disorders, thus suggesting the opportunity of an accurate follow-up in order to identify possible risk factors for cardiovascular disease and thromboembolism.
Exp Clin Endocrinol Diabetes 2000
PMID:Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's syndrome and in patients with adrenal incidentaloma. 1096 61

Diabetes mellitus (DM) type 2 is a very strong risk factor for atherosclerosis. The final event of atherosclerosis is the vessels occlusion by platelet riche thrombus. Platelets adhesion and aggregation is mediated by interaction between platelets glycoproteins: GPIb-IX, GPIIb-IIIa and adhesive proteins: von Willebrand factor or fibrinogen. The expression of platelets GPIb-IX, GPIIb-IIIa, plasma vWF, fibrinogen concentrations were evaluated in 40 patients with diabetes type 2 (22 patients with PAOD stage II and IV according to Fontain, 18 diabetics without paod) and 32 healthy individuals. The expression of platelets glycoproteins GPIIb-IIIa and GPIb-IX was estimated by ELISA using monoclonal antibody against GPIIb-IIIa (CD41a) and GPIb-IX (CD 42a Immunotech). Plasma vWf (189.7 +/- 53.6%), fibrinogen (4.5 +/- +/- 1.3 g/l) level and expression of platelets GPIb-IX (63.2 +/- 19.6% in platelets concentration 125,000/mm3, 104.5 +/- 28.1% in platelets concentrations 250,000/mm3) and GPIIb-IIIa 50.8 +/- 10.1% in platelets concentrations 125,000/mm3, 95.3 +/- 21.3% in platelets concentrations 250,000/mm3 were statistically higher in patients with diabetes type 2 than in controls (vWf: 94.9 +/- 27.1%, fibrinogen: 2.8 +/- 0.4 g/l, GPIb-IX in platelets concentration 125,000/mm3: 43.8 +/- 9.3%, in concentration 250,000/mm3: 83.9 +/- 18.3%, GPIIb-IIIa in platelets concentration 125,000/mm3: 33.7 +/- 10.1%, in platelets concentration 250,000/mm3: 63.2 +/- 15.4%). We found significant correlation between the expression of GPIIb-IIIa, GPIb-IIIa, GPIb-IX and plasma adhesive proteins: vWF, fibrinogen in controls and both subgroups of diabetic patients. The correlation between plasma vWF and fibrinogen level and degree of arterial insufficiency in diabetic patients was also found. We can assume that higher vWf, fibrinogen plasma level in diabetic patients with and without PAOD could account for high expression of platelets GPIIb-IIIa and GPIb-IX.
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PMID:[Chronic peripheral arterial occlusive disease, platelet glycoproteins GPIIb-IIIa and GP Ib-IX, plasma von Willebrand factor and plasma fibrinogen concentrations in patients with type 2 diabetes mellitus]. 1123 40

Oxidative stress and defective fatty acid metabolism in diabetes may lead to impaired nerve perfusion and contribute to the development of peripheral neuropathy. We studied the effects of 2-week treatments with evening primrose oil (EPO; n = 16) or the antioxidant alpha-lipoic acid (ALA; n = 16) on endoneurial blood flow, nerve conduction parameters, lipids, coagulation, and endothelial factors, in rats with streptozotocin-induced diabetes. Compared with their nondiabetic littermates, untreated diabetic rats had impaired sciatic motor and saphenous sensory nerve-conduction velocity (NCV; P <.001), reduced endoneurial blood flow (P <.001), and increased serum triglycerides (P <.01), cholesterol (P < 0.01), plasma factor VII (P <.0001), and von Willebrand factor (vWF; P <.0001). Plasma fibrinogen and serum high-density lipoprotein concentrations were not significantly different. Treatment with either ALA or EPO effectively corrected the deficits in NCV and endoneurial blood flow. ALA was associated with marked and statistically significant decreases in fibrinogen, factor VII, vWF, and triglycerides (P <.01, paired t tests before v after treatment). In contrast, EPO was associated with significant (P <.05) increases in fibrinogen, factor VII, vWF, triglycerides, and cholesterol and a significant decrease in high-density lipoprotein. Changes in levels of coagulation factors and lipids, qualitatively similar to those found with EPO, were obtained with a diet containing sunflower oil (to control for calorific and lipid content) or with a normal diet alone. Blood glucose and hematocrit levels were not significantly altered by treatments. These data suggest that although both ALA and EPO improve blood flow and nerve function, their actions on vascular factors differ. The marked effects of ALA in lowering lipid and hemostatic risk factors for cardiovascular disease indicate potential antithrombotic and antiatherosclerotic actions that could be of benefit in human diabetes and merit further study.
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PMID:The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat. 1147 72

Uncomplicated Type 1 (insulin-dependent) diabetes mellitus is characterized by generalized vasodilatation. Its possible correlates, increased microvascular permeability and endothelial dysfunction, have been associated with long-term complications. The objective was to study the effects of acute hyperglycemia and hyperinsulinemia, both separately and in combination, on skin microvascular flow, capillary permeability, capillary recruitment, and endothelial dysfunction in Type 1 diabetes mellitus. Sixteen Type 1 diabetic patients (all normoalbuminuric, no (pre-)proliferative retinopathy) underwent a euglycemic (glucose target 5.0 mmol/L, insulin infused at 30 mU x kg(-1) x h(-1)), a hyperglycemic (glucose target 12.0 mmol/L, insulin 30 mU x kg(-1) x h(-1)), a hyperinsulinemic (glucose target 5.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)), and a hyperglycemic-hyperinsulinemic (glucose target 12.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)) clamp on separate days, in random order. Skin microvascular flow was measured by laser Doppler flowmetry. Capillary permeability and density were determined by large-window sodium-fluorescein videodensitometry. Increases in serum soluble intercellular adhesion molecule-1 (sICAM-1) and plasma von Willebrand factor antigen (vWF-Ag) were considered to represent abnormal endothelial function. Hyperglycemia (P < 0.01) and hyperinsulinemia (P < 0.05) as well as both interventions combined (P < 0.001) induced an increase in laser Doppler flow, without capillary recruitment. Transcapillary leakage of sodium-fluorescein and sICAM-1 and vWF-Ag levels were unaffected by hyperglycemia or hyperinsulinemia. Microvascular permeability appears to be determined primarily by properties of the capillary wall and not by acute changes in local hemodynamics. The acute hyperglycemia- and hyperinsulinemia-induced vasodilatation is not accompanied by changes in microvascular permeability or endothelial markers.
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PMID:Acute hyperglycemia and hyperinsulinemia enhance vasodilatation in Type 1 diabetes mellitus without increasing capillary permeability and inducing endothelial dysfunction. 1174 67

Human diabetic neuropathy is multifactorial in etiology, with ischemia as a final common pathology. Although impaired vascular endothelial cell function in diabetic microvascular injury is established, the role of thrombomodulin (TM)-dependent protein C antithrombotic mechanism in the pathogenesis of neuropathy is unclear. This neuropathologic case-control study investigated whether vascular endothelial TM expression is deficient in peripheral nerve microvessels in diabetic neuropathy. Sural nerve biopsies from 7 patients with diabetic neuropathy and 10 with axonal neuropathy without vasculopathy were immunostained with anti-TM and anti-von Willebrand factor (vWF; an endothelial cell marker) antibodies. The proportion of TM-positive microvessels was expressed relative to total vWF-staining vessels, according to vessel caliber and regional distribution within the nerve. In diabetic nerves compared with reference controls, the proportion of TM-positive endoneurial microvessels was 15-fold lower (0.02 vs. 0.30 in diabetic nerves vs. controls, P < 0.004), and the proportion of small-caliber epineurial microvessels was 10-fold lower (0.04 vs. 0.43, P < 0.001). No TM expression was detected at the perineurium in diabetic or control nerves. We demonstrate a substantial reduction of vascular endothelial TM expression throughout human diabetic neuropathy. These findings suggest that an impaired native TM-dependent protein C antithrombotic mechanism may contribute to microvascular ischemia in the pathogenesis of diabetic neuropathy.
Diabetes 2002 Jun
PMID:Thrombomodulin deficiency in human diabetic nerve microvasculature. 1203 86

Lower extremity ischemia is one aspect of atherosclerosis, a disease associated with both inflammation and hypercoagulability. Many recent studies have focused on a diversity of mechanisms by which inflammation can promote blood clotting. However, it has not been proven that inflammation can actually trigger clinically relevant thrombus formation in vivo. The purpose of the study was to determine the plasma levels of markers of inflammation and their possible association with markers for coagulability with special emphasis on the difference between patients with and without diabetes. Forty-six patients, 20 diabetics and 26 without diabetes scheduled for lower extremity revascularisation were examined by preoperative blood sampling. A strong positive correlation between C-reactive protein (CRP) and fibrinogen was found, particularly in diabetics. A high fibrinogen level was not associated with other markers of hypercoagulability, Thrombin-Antithrombin (TAT), Prothrombin Fragment 1+2 (F 1+2) and D-dimer although the latter three correlated with each other. There was also a correlation between von Willebrand antigen (vWF) and CRP, also in this case the relationship was dependent on the findings in patients with diabetes. It is concluded that there is a difference between diabetic and nondiabetic patients with lower limb ischemia with the former showing stronger signs of inflammation.
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PMID:Markers of inflammation and hypercoagulability in diabetic and nondiabetic patients with lower extremity ischemia. 1206 38

The effects of two third-generation monophasic combined oral contraceptives (COC) and a postmenopausal hormone replacement therapy (HRT) consisting of 2 mg 17 beta-oestradiol on the plasma level of the acute-phase indicator C-reactive protein (CRP) and other acute-phase reactants were analysed. Two studies were conducted: (1) a randomised, open-label study with two different oral contraceptive preparations with an equal dose of ethinylestradiol (30 micrograms) and a different progestogen, either 75 micrograms gestodene (GSD-EE) or 150 micrograms desogestrel (DSG-EE); blood samples of 39 young women were analysed before and after 3, 6, 12 treatment cycles; (2) a randomised, blinded placebo-controlled study with 2 mg 17 beta-oestradiol in postmenopausal women with non-insulin-dependent diabetes mellitus without signs of cardiac involvement; blood samples of 38 women were analysed before and after 6 weeks of treatment. The plasma concentration of CRP increased strongly during oral contraceptive use for both preparations; the increase persisted over 12 cycles. The already elevated CRP in postmenopausal diabetic women showed a moderate increase after 6 weeks of treatment with 17 beta-oestradiol. CRP increases during oral contraceptive use were associated with changes in some other acute-phase proteins (fibrinogen, ceruloplasmin, von Willebrand factor [vWF]) originating from the liver and vessel wall, but not in others (interleukin-6 [IL-6], serum amyloid A [SAA]). The results demonstrate an increase in a specific set of acute-phase reactants caused by oestrogen-containing preparations. It is proposed that the pro-inflammatory effect of oestrogens should be checked for a relationship with the increased risk of thromboembolism for both oral contraceptive and HRT.
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PMID:Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment. 1261 83

Patients with primary hyperparathyroidism (PHPT) have impaired vasodilation both dependent and independent of endothelium. The aims of our study were to measure three different biochemical markers of endothelial activation, i. e., plasma thrombomodulin, soluble(s) E-selectin, and von Willebrand factor, in PHPT patients before and one year after successful parathyroidectomy, and to distinguish the potential effect of hypercalcemia and/or high parathyroid hormone from that of major cardiovascular risk factors (diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking habit) on endothelial function. Twenty consecutive patients with PHPT subdivided into two groups according to the absence (n = 8) or presence (n = 12) of one or more risk factors, and fifteen healthy normocalcemic subjects were studied. Baseline thrombomodulin levels were similar in the groups with and without risk factors, and in controls. In contrast, sE-selectin and von Willebrand factor were higher in PHPT patients with risk factors than in those without risk factors (p < 0.05 and p < 0.01, respectively) and controls (p < 0.01). Neither thrombomodulin nor sE-selectin changed after parathyroidectomy in either PHPT group. Plasma von Willebrand factor decreased (p < 0.01) in patients without risk factors, while persisting at high levels in patients with risk factors. In conclusion, in spite of a limitation due to the small number of patients, our study suggests that classic cardiovascular risk factors seem to be the main determinants for the high plasma levels of sE-selectin and vWF in PHPT. Together with unaltered thrombomodulin and sE-selectin levels, a plasma vWF decrease after parathyroidectomy might reflect a specific mechanism of its endothelial calcium- and/or PTH-stimulated secretion in some PHPT patients without risk factors. Whether a vWF reduction after parathyroidectomy may be used as a biochemical index for improved endothelial function in PHPT patients without risk factors has yet to be demonstrated in larger studies.
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PMID:Biochemical markers of endothelial activation in primary hyperparathyroidism. 1652 14


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