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

Diabetes mellitus (DM) is characterized by a hypercoagulability state and many of these disorders are corrected with adequate metabolic control. The goal of this study was to assess diverse hemostatic and fibrinolytic parameters in 12 insulin-dependent (IDDM) metabolically controlled patients without vascular lesions and in a group of 12 healthy volunteers. A significant difference was observed in the euglobulin lysis time (ELT), after a stress test, since only 3 patients had an adequate fibrinolytic response. These results suggest that the fibrinolytic alterations found in DM are not secondary to metabolic disorders caused by the disease and we can consider that the existence of subclinical alterations of the vascular endothelium would be responsible for these alterations.
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PMID:[Diabetes mellitus and changes in hemostasis: study of the fibrinolytic response of insulin-dependent patients without vascular disease]. 271 90

IgA and IgG antibodies against cardiolipin and/or phosphatidylserine were detected in the sera of patients with non insulin-dependent (type 2) diabetes mellitus. The highest prevalence was observed in particular in patients with macrovascular complications (86%). A significant increase of platelet bound IgA and IgG was observed also in patients with sera positive for anti-phospholipid antibodies suggesting the coexistence of reactivity against phospholipid and platelets. Several reports have focused on a new clinical entity characterized by the presence of anti-phospholipid and by a tendency to venous and arterial thrombosis. In addition to their acute thrombogenic effects, we suggest that anti-phospholipid antibodies may play a role in the impairment of the thromboresistant property of vascular endothelium and in the enhancement of platelet aggregation leading to the pathogenesis and/or progression of the macrovascular diabetic complications.
Diabetes Res 1989 Feb
PMID:Detection of anti-phospholipid (cardiolipin, phosphatidylserine) antibodies in the serum of patients with non insulin-dependent (type 2) diabetes mellitus and macroangiopathy. Coexistence of anti-platelet reactivity. 274 10

Because diabetic vascular disease is accompanied by a state of hypercoagulability, manifested by increased thrombin activity and foci of intravascular coagulation, we investigated whether a specific procoagulant property of the endothelium--production and surface expression of tissue factor--is modified by elevated glucose concentrations. In unperturbed human vascular endothelial cells, tissue factor mRNA and expression of the functional protein were undetectable and were not induced by 10-12 days of exposure to 30 mM glucose. In thrombin-stimulated cultures, tissue-factor expression was related inversely to cellular density, with confluent cultures producing (per 10(5) cells) half the amount of tissue factor measured in sparse cultures. Cells exposed to high glucose and studied when cell number and thymidine incorporation were identical to control cells manifested increased tissue-factor mRNA level and functional protein production in response to thrombin (P = .002). This effect was not attributable to hypertonicity and was not observed after short exposure to high glucose. In contrast, the tissue-factor response to interleukin 1, a modulator of endothelial function in the context of host defense, was decreased in cells cultured in high glucose (P = .04). These findings indicate that exposure to high glucose can alter tissue-factor gene expression in perturbed vascular endothelium. The reciprocal effects of high glucose on the tissue-factor response to thrombin and interleukin 1 points to different pathways of tissue-factor stimulation by the two agents and suggests functional consequences pertinent to the increased thrombin activity and compromised host-defense mechanisms observed in diabetes.
Diabetes 1989 Feb
PMID:Modification of tissue-factor mRNA and protein response to thrombin and interleukin 1 by high glucose in cultured human endothelial cells. 278 75

Endothelial cells form the intimal lining of the entire vascular system. The vascular endothelium is continuously and directly bathed by components of the bloodstream and represents the initial fixed anatomical surface with which these components come in contact. In the past decade, the methodologies for studying endothelial cell functions have markedly advanced, enabling direct and detailed study of the vascular endothelium. From such studies, it is now apparent that the vascular endothelium represents an extraordinarily complex network of cells demonstrating a multitude of distinct anatomic, metabolic, and immunologic properties critical to such processes as angiogenesis, atherosclerosis, thrombosis, neoplasia, and a variety of metabolic disorders including homocystinuria and diabetes mellitus. This report will focus on the interactions of insulin and the insulin-like growth factors (IGFs) with vascular endothelium, based on studies with cultured endothelial cells, isolated microvessels, and perfused organ systems. Data will be presented relevant to the following concepts: (1) endothelial cells, in culture and in vivo, have specific receptors for insulin, IGF-I, and IGF-II; (2) insulin, IGF-I, and IGF-II have both distinct and overlapping functions in cultured endothelial cells; (3) cultured endothelial cells process receptor-bound insulin, IGF-I, and IGF-II, by distinct processes; (4) in vivo, capillary endothelial receptors are integrally involved in the transport of intact insulin to subendothelial sites of insulin action; and (5) vascular endothelium has specialized cellular features that are likely to contribute to the unique interactions of endothelial cells with insulin and the IGFs.
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PMID:Insulin, insulin-like growth factors, and vascular endothelium. 297 48

Cholecystokinin (CCK) is a known stimulus for the release of insulin and other islet hormones. To localize islet cell CCK binding sites, we measured the uptake of 125I-CCK by the isolated, perfused rat pancreas. Light microscope autoradiographs revealed uptake of label over both the endocrine islets of Langerhans and the exocrine acini. This uptake of 125I-CCK was saturable, as it decreased markedly when a large excess of unlabeled CCK8 was included in the perfusion solution. To define which cells in the islets bound CCK, electron microscope autoradiographs were prepared. The majority of silver grains in islets were localized over beta cells (69%), although saturable uptake was also observed over alpha (12%) and other islet cells. When grain densities were analyzed (grains/micron 2), the highest density was observed over islet blood vessel cells. In contrast to islet blood vessels, there was no localization of 125I-CCK over acinar blood vessels. This study supports the concept, therefore, that there is a direct regulation of islet endocrine cells by CCK, and also raises the possibility that CCK influences islet hormone release via an indirect effect on the islet vascular endothelium.
Diabetes 1985 Apr
PMID:Localization of saturable CCK binding sites in rat pancreatic islets by light and electron microscope autoradiography. 298 85

Arachidonic acid (AA) is metabolized by the cyclo-oxygenase and the lipoxygenase pathways to give a number of products, some of which have potent and sometimes opposing biological activities. Different cell types produce different metabolites, so that the chief AA metabolite produced by the platelet is the pro-aggregatory thromboxane A2 (TXA2), whereas that produced by the vascular endothelium is the anti-aggregatory prostacyclin. White blood cells, on the other hand, are the chief source of the leukotrienes, which are implicated in the inflammatory process. Generation of these products may be modified in certain pathological conditions, such as atherosclerosis and diabetes, where prostacyclin synthesis is reduced and TXA2 synthesis increased, resulting in a pro-thrombotic state. Synthesis of AA metabolites may be inhibited, either totally or selectively, using drugs which inhibit different enzymes in the metabolic pathway. These drugs may be beneficial in the treatment of thrombotic disorders and inflammation. AA metabolism may also be modified by dietary substitution with eicosapentaenoic acid, a fatty acid present in fish oils.
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PMID:Arachidonate metabolism in blood cells and the vessel wall. 301 65

Following our observations that non-esterified fatty acids (NEFAs) inhibit prostacyclin (PGI2) synthesis and accelerate PGI2 degradation, we have examined the possibility that NEFAs may also affect the activity of vascular ADPase, which converts the platelet pro-aggregatory adenosine diphosphate (ADP) to adenosine, an inhibitor of aggregation and a vasodilator. Incubation, in buffer solutions, of NEFAs with intact rat aortic rings significantly inhibited vascular ADPase activity. This inhibition was more marked at higher NEFA concentrations and with unsaturated fatty acids (linoleic, oleic) than with a saturated fatty acid (stearic). This NEFA-mediated inhibition of vascular ADPase activity could be prevented by the prior addition of fatty acid-free human albumin to the incubate. Similarly, the vascular rings recovered from NEFA-mediated inhibition by washing and further incubation in NEFA-free buffer. Therefore, elevated NEFA concentrations inhibit, reversibly, an enzyme system which is thought to protect the vascular endothelium. The NEFA-mediated inhibition of ADPase activity was also confirmed following incubation of rat aortic rings in human serum enriched with exogenous NEFA. These findings provide further evidence that NEFAs may contribute to the pathogenesis of vascular disease associated with diabetes mellitus and of other conditions where an elevation of serum NEFA concentrations occurs.
Diabetes Res Clin Pract
PMID:The effect of non-esterified fatty acids on vascular ADP-degrading enzyme activity. 302 42

Angiotensin-converting enzyme (ACE) is secreted by the vascular endothelium and serum activity may reflect endothelial damage. A study of 48 insulin-dependent diabetics, 15 with and 33 without evidence of diabetic retinopathy and 41 non-diabetic controls was performed. ACE activity was significantly elevated in the diabetics compared with controls (mean +/- SD 46 +/- 14 vs 35 +/- 9 U/l, p less than 0.001) (units in micromoles substrate converted/min/l serum). This elevation was more marked in diabetics with such evidence of microangiopathy as retinopathy or raised albumin excretion rate (AER) (51 +/- 14 U/l, p less than 0.0001), and also in those with raised AER alone (47.2 +/- 15 U/l, p less than 0.002). Patients with both raised AER and retinopathy had significantly higher ACE activities than those with no complications (53 +/- 15 vs 41.2 +/- 15 U/l, p less than 0.05). No correlation was found with glycosylated haemoglobin or smoking habits. We conclude that mean serum angiotensin converting enzyme activity is increased in insulin-dependent diabetes, particularly in those with evidence of microangiopathy and this may reflect microvascular damage.
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PMID:Angiotensin-converting enzyme (ACE): relationship to insulin-dependent diabetes and microangiopathy. 303 Jun 21

The evidence that hyperinsulinaemia represents an independent risk factor for cardiovascular disease is tantalizing but the hypothesis cannot be said to be proven. The inconsistencies arising from the major prospective studies require that further work be done. Hyperinsulinaemia may not carry the same implications in all subjects and its interactions with other risk factors and with blood glucose are not well described. Possible further research has been discussed and outlined at a recent meeting (Colwell, 1985). The suggestions include delineating the action of growth factors and insulin in defined serum-free tissue culture, and the use of more sophisticated culture models, such as smooth muscle covered by vascular endothelium. The choice of human or primate tissue is desirable because of the species specificity of the atherosclerotic lesions. Prospective trials of modifying peripheral insulin levels in treated diabetic patients are probably still impracticable. The case for attempting to achieve normoglycaemia in diabetes to avoid microvascular complications is strong, and current insulin treatment regimens accept peripheral hyperinsulinaemia as a consequence of achieving portal insulin concentrations sufficient to suppress hepatic glucose output. It is hard to envisage a trial to examine reduced peripheral insulin concentrations which would not give unacceptably poor blood glucose control. Current studies of different methods and degrees of control of blood glucose might be used to provide some indication of whether such a trial could ever be justified. The Diabetes Control and Complication Trial (DCCT) is a prospective multicentre study of intensive versus conventional insulin treatment in insulin-dependent diabetic patients in the USA, and the UK Prospective Study of therapies of maturity onset diabetes (UKPS) is following patients not satisfactorily controlled on diet, randomized to different treatment modalities. These may produce some evidence within the next few years, on insulin concentrations and complications (Tattersall and Scott, 1987). Should any of this change current management of non-insulin-dependent diabetes? Despite claims of enthusiasts, special treatment regimens with intensive exercise, a particular oral agent or the addition of sulphonylureas to insulin therapy are either not generally applicable or have little theoretical basis (Martin, 1986). Current 'good practice' in Europe as put forth in a consensus document (Alberti and Gries, 1988), recognizes the need to address risk factors other than diabetes in the management of the non-insulin-dependent diabetic patient.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Macrovascular disease and hyperinsulinaemia. 307 99

Factor VIII/von Willebrand antigen (VA), part of the molecule of plasma factor VIII, realizes the interaction between platelets and vascular endothelium and the triggering of primary hemostasis. The modern diagnostics and treatment of the complicated acquired thrombocytopathies are impossible without the investigation on the concentration of factor VIII/von Willebrand antigen. The immune coagulation method used allows the objective, exact and fast determination of VA--referent values have been developed in healthy subjects. The patients with blastic leukosis studied--28 and with chronic myeloleukemia--18, all with severe endogenous complicated thrombocytopathy, functionally and biochemically confirmed, showed normal values of VA/von Willebrand antigen. On the contrary, a slightly elevated VA was established in patients with diabetes with no vascular-degenerative syndrome, corresponding to the activation of platelet functions and to enhanced adhesiveness in particular, contributing to thrombotic complications. The data obtained are discussed in connection with the etiopathogenesis of the separate kinds of thrombocytopathies and the necessity of substitutive therapy.
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PMID:[Factor VIII (von Willebrand antigen) in patients with acquired thrombocytopathies]. 311 Oct 97


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