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

Diabetic subjects tend to develop microvascular complications believed to be due to platelet hyperaggregability. This increased platelet sensitivity is though to be the result of an imbalance of PGI2 and TXA2 production in diabetes. This study sought to determine whether megavitamin E supplementation could restore PGI2/TXA2 balance in streptozotocin-diabetic rats. Endogenous release of PGI2 by isolated aorta, determined via radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha, was significantly greater (P less than 0.05) in rats receiving 100x the normal vitamin E requirement than in untreated diabetic rats. PGI2 synthesis was negatively correlated with plasma glucose levels (r = -0.87, P less than 0.05) in non-fasted rats at sacrifice. Vitamin E supplementation, at both the 10x and the 100x level, significantly depressed (P less than 0.05) thrombin-stimulated synthesis of TXA2 in washed platelet. PGI2 and TXA2 production were expressed as a ratio. Megavitamin E therapy appears to increase this ratio over that seen in the diabetic animal. The data suggest that vitamin E, at high levels, exerts an ameliorating influence of the PGI2/TXA2 imbalance of diabetes.
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PMID:Differential effects of megavitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats. 635 Jan 38

Alloxan-induced diabetes and platelet aggregation were studied in male Sprague-Dawley rats. Platelets from diabetic rats receiving insulin (one unit protamine-zinc insulin/100 g BW) were consistently more responsive to aggregating agents (ADP, thrombin) than platelets from control rats (with or without insulin administration). Also, serotonin release from platelets was consistently greater in diabetic compared to control rats following thrombin-stimulated platelet aggregation.
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PMID:Experimental diabetes and platelet aggregation in the rat. 635 54

The relationship between platelet abnormalities and vessel wall changes in diabetes is not known. We have examined the time course of alterations in in vitro platelet function and endothelial damage, as assessed by measurement of plasma levels of von Willebrand factor (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag), in streptozotocin-induced diabetic rats. Platelet aggregation and the platelet release reaction in response to ADP, thrombin, and collagen were measured in suspensions of washed platelets prepared from rats 3, 7, 14, or 28 days after induction of diabetes and in control animals. Platelets from diabetic animals showed enhanced aggregation response to ADP as early as 3 days after induction of diabetes and became hyperresponsive to thrombin after 7 days, compared to control platelets. Thrombin-induced release of serotonin was greater in platelets from diabetic animals at 14 days. Collagen-induced responses were not different at any time studied. VIIIR:WF was determined by ristocetin-induced platelet agglutination time in gel-filtered platelets, and VIIIR:Ag was determined by immunoelectrophoretic technique. VIIIR:WF and VIIIR:Ag were significantly enhanced in plasma from rats at 28 days after induction of diabetes and VIIIR:Ag was enhanced in plasma from rats at 14 days after induction of diabetes, but at the earlier times studied, neither were different from values in plasma from control-treated rats. Changes in VIIIR:WF and VIIIR:Ag therefore occurred later than the changes in platelet function. Plasma cholesterol concentrations were not significantly different at any of the times studied, but plasma triglyceride concentrations were significantly increased at 3 days and remained increased with further durations of diabetes. This may have contributed to the observed platelet and vessel wall changes. If these in vitro alterations reflect in vivo behavior, then platelet alterations occur before vessel wall changes and therefore do not appear to be a consequence of such changes in experimental diabetes mellitus.
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PMID:Time course of changes in in vitro platelet function and plasma von willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag) in the diabetic rat. 641 93

An evaluation of platelet and vascular (aortic) arachidonic acid metabolism was performed in Lewis male rats rendered diabetic by injection of streptozotocin, and the results were compared to those in matched controls. Parameters evaluated included the release of this fatty acid from prelabeled platelets and aortas and conversion of labeled fatty acid to thromboxane B2 and 6-keto-PGF1 alpha in platelets and aortas, respectively. Diabetic rat platelets showed markedly increased release of arachidonic acid with thrombin used as the aggregating stimulus. Conversion of arachidonic acid to thromboxane B2 was slightly, but not significantly, higher in the diabetic rats. In the vessel, thrombin-stimulated release of arachidonic acid was slightly, but not significantly, increased in the diabetic animals when compared to controls. This finding was associated with a decrease in vascular production of 6-keto-PGF1 alpha both in vascular tissues incubated with arachidonic acid alone and in vascular tissues incubated with thrombin. The changes observed both in platelet and vascular metabolism of arachidonic acid were corrected by islet issue transplantation, suggesting a disease-specific effect. The changes observed in arachidonic acid metabolism suggest a significant imbalance in thromboxane A2 and PGI2 production in diabetic rats. Such changes might promote the development of the microvascular changes seen in diabetes mellitus.
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PMID:Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats. 644 27

A case of acute intestinal vascular necrosis in a 19-year-old user of oral contraceptives (OCs) is described, and hypotheses explaining the digestive complications of synthetic estrogens are reviewed. The patient had originally presented with a violent gastric pain that subsequently spread to the entire abdomen. An abrupt worsening of her condition involved cardiovascular collapse associated with a peritoneal syndrome, vomiting and dehydration, and hyperleukocytosis. Emergency opening of the peritoneum was followed by evacuation of a large quantity of fetid gas and alimentary debris, and observation of a completely necrosed stomach. A careful lavage of the entire intestinal cavity led to temporary improvement, but it became clear during an attempt at gastrectomy that further treatment would be unavailing and the patient died shortly thereafter. Estrogens were believed to be responsible for the digestive necrosis because it occurred in a young woman who had used an estrogen-rich OC for 3 years and who smoked; a hapatic biopsy confirmed the diagnosis. No traces of other risk factors such as hypertension, hyperlipidemia, diabetes, neoplasia, or obesity were observed. Recent publications indicate that OCs are responsible for a certain number of digestive problems, which may include acceleration of intestinal transit, severe diarrhea, rectorrhagia, ischemic or ulcerative colitis, intestinal infarct which is usually localized, and hepatocellular problems ranging from moderate hepatic insufficiency to malignant tumor and Budd-Chiari syndrome. OCs do not modify hemodynamic regimes, but they may cause elevation of fibrinogen and thrombin, diminution of antithrombin III acitivty, increased platelet adhesivity, and decreased fibrinolysis leading to hypercoagulability. These modifications in hemostasis occur in all OC users and are not statistically correlated with occurence of thrombotic accidents. OCs are probably responsible for parietal vascular lesions; experimental injection of synthetic estrogens is associated with both arterial and venous lesions. The most characteristic anomaly is at the level of the intima, with proliferation of smooth muscle cells and increased conjunctive tissue fibers associated with proliferation of the media or the endothelium. The absence of lipid deposits, the simultaneous appearance of arterial and venous lesions, and other evidence argues against and atheromatous origin of parietal lesions. A significant correlation has been found between high levels of anti-synthetic ethinyl estradiol antibodies and the presence of vascular lesions. It is hypothesized that these circulating immune complexes penetrate the vascular walls of OC users and produce lesions, which may depend on factors such as smoking.
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PMID:[Digestive complications of oral contraceptives: a case of extensive digestive necrosis in a young woman]. 647 54

Fibrin catabolism was measured during the pregnancy of insulin-dependent diabetic women in both a longitudinal and cross sectional fashion. Samples of maternal peripheral venous blood were obtained in 20 pregnant diabetic women between 26 and 38 weeks' gestational age. Fibrinopeptide A, the first peptide cleaved from fibrinogen during thrombin-mediated catabolism, was measured by radioimmunoassay. Intra-assay and interassay variation for fibrinopeptide A in this laboratory were 2% and 4% respectively. Antithrombin III activity was determined by the method of Odegaard. The patients ranged from 23 to 36 years. Overall blood glucose control was good as reflected in near-normal HbA1 fasting plasma glucose values. The mean HbA1 +/- 1 standard deviation was 7.1% +/- 1.2%. The mean fasting plasma glucose concentration was 101.9 mg% +/- 21.5 mg%. Mean FPA for the diabetic women exceeded control values at each gestational period. Significant differences were found in four of the seven intervals. While the highest FPA was noted in a patient with advanced diabetic vasculopathy, exclusion of this patient did not alter the overall findings. The findings were striking and suggest the need for a prospective study designed to account for White's classification of diabetes and the degree of glucose control. Because complications of the diabetic pregnancy include an increased risk of hypertension in the mother and sudden, unexplained fetal loss, two complications associated with abnormal clotting, the increase in fibrin catabolism in patients in tight metabolic control would suggest that events other than glucose regulation impact upon fibrin catabolism and possibly pregnancy outcome in the diabetic mother.
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PMID:Fibrin generation during the diabetic pregnancy. 651 59

To counter the paucity of documention on thromboembolic disorders caused by oral contraceptives (OC), a case study is presented describing the incidence of occlusion of arteria centralis retinae in a 24-year old woman after prolonged use of an OC, Bisecurin. She had taken Bisecurin for 4.5 years and had gained 20 kg during that time, but stopped usage 1 month before admission. She was hospitalized with severe deterioration of vision in the left eye. An eye examination indicated an edematous condition of the retina and reddening of the macula. Acuity of vision value for the left eye was .01 vs. 1.0 for the right, which was confirmed by fluorescein fundus angiography. Moderately decreased antithrombin III (AT III) activity was also ascertained. Treatment consisted of immediate retrobulbar injection with Tolazolin followed by Rheomacrodex, Cavinton infusions, B1 and B12 injections, Oradexon subconjunctival injection as well as vitamin B complex, Cavinton, and Colfarit tablets and a fat-free diet. Significant improvement of the left eye condition appeared 4 weeks later. Periodic follow-ups showed the healing of the condition around the macula; however, the patient suffered permanent damage to the retina due to the arterial occlusion above and below the macula. The disturbed lipid values of metabolism were also returned to normal, as borne out by normal dextrose loading results 8 months later (glucose tolerance was abnormal during examination at admission). The estrogen and progesterone components of OCs have been shown to reduce AT III levels, shorten heparin-thrombin coagulation time, increase fibrinogen levels, decrease HDL cholesterol levels, and produce excess TXA2 (thromboxan) resulting in vasoconstriction and thrombocyte aggregation. The risk of thrombosis is 6 times higher in OC users than in nonusers, although other susceptibility factors (obesity, diabetes, hypertension) also contribute to thrombosis.
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PMID:[Arterial occlusion in the ocular fundus induced by oral contraceptives]. 651 54

Platelet vitamin E content and thromboxane A2 (TxA2) synthesis have been investigated in type I diabetic subjects and age- and sex-matched controls. Platelets, but not plasma, from diabetic subjects contained significantly lower vitamin E levels and synthesized significantly greater amounts of TxA2 when challenged with collagen or thrombin than platelets from control subjects. Conversion of exogenously added arachidonic acid to TxA2 was unaltered between platelets from control and diabetic groups. Platelet vitamin E content from control and diabetic groups combined exhibited a significant negative linear correlation with collagen- and thrombin-induced TxA2 production. These data suggest that low platelet vitamin E levels could be a contributing factor to the increased thromboxane synthesis demonstrated by platelets from the above type I diabetic subjects.
Diabetes 1984 Mar
PMID:Interrelation of platelet vitamin E and thromboxane synthesis in type I diabetes mellitus. 669 15

The effect of nonenzymatic glycosylation on the biologic function of human antithrombin III was evaluated using a chromogenic thrombin substrate assay in the presence of catalytic amounts of heparin. Experimental conditions that increased the rate of nonenzymatic protein glycosylation were associated with decreases in the thrombin-inhibiting activity of antithrombin III. This glycosylation-induced inhibition of heparin-catalyzed antithrombin III activity was completely reversible by preassay incubation with excess sodium heparin. These observations provide a biochemical explanation for the heparin-reversible, accelerated fibrinogen disappearance rate induced by hyperglycemia in diabetic patients. Defective inhibition of the coagulation cascade induced by excessive nonenzymatic glycosylation of antithrombin III in vivo could contribute to accumulation of fibrin in various diabetic tissues.
Diabetes 1984 Jun
PMID:Inhibition of heparin-catalyzed human antithrombin III activity by nonenzymatic glycosylation. Possible role in fibrin deposition in diabetes. 672 50

Plasma levels of platelet factor 4 (PF4) determined in 58 apparently healthy subjects were found to increase with age. In 66 insulin dependent diabetics, PF4 plasma levels were increased but unrelated to the age of subject. Mean fibrinopeptide A levels were elevated in the diabetics but not correlated to PF4 levels. Activation of the coagulation system with thrombin generation thus seems to be operative in diabetes, but the enhanced platelet activation also observed in this disease is probably not thrombin mediated. No correlation was found between PF4 plasma concentration and the degree of vascular complication, HbA1C, blood glucose, 24-h urinary glucose, serum cholesterol or serum triglycerides.
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PMID:Enhanced in vivo platelet activation in diabetes mellitus. 675 24


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