Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with diabetes mellitus are several fold more prone to various forms of vascular diseases than are the non-diabetic subjects. Because platelets are in the key position in thrombus formation and possibly in atherogenesis, much interest has focused on the role of platelets in the development of diabetic vascular disease. Most studies on this topic have suggested increased adhesiveness and aggregability of the platelets from diabetic patients. The increased production of von Willebrand factor may account for the enhanced adhesion. The shift of the balance between proaggregatory thromboxane A2 and antiaggregatory prostacyclin to the dominance of thromboxane A2 could explain the increased aggregability of diabetic platelets, but the data available at the moment do not allow the conclusion that such a change really exist in human in vivo. One recent work has suggested that the increased glycosylation of connective tissue proteins in diabetes would increase their aggregating potency, but also this finding needs further confirmation.
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PMID:Platelet function and thrombus in diabetes. 391 1

Diabetes mellitus is associated with altered platelet function and endothelial damage, but their relationship remains unclear. We examined the effect of short-term metabolic control with insulin in 14- and 28-day streptozocin-induced diabetic rats on alterations in in vitro platelet aggregation and serotonin release. Endothelial damage was assessed by plasma concentrations of von Willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag). Insulin was administered for 5 or 7 days at 9 or 21 days, respectively, after streptozocin. Enhanced platelet aggregation responses to adenosine diphosphate (ADP) and thrombin occurred after both durations of diabetes. Insulin therapy returned ADP-induced, but not thrombin-induced, responses to normal. Enhanced thrombin-induced platelet release of serotonin occurred at both times. Collagen-induced platelet release was enhanced in 28-day diabetic rats. Insulin therapy returned these responses to normal. Plasma concentrations of VIIIR:WF and VIIIR:Ag were elevated in 28-day, but only VIIIR:WF was elevated in 14-day diabetic rats. Insulin therapy reduced the elevated levels of VIIIR:Ag in 28-day diabetic rats, but had little effect on either parameter after the shorter duration of diabetes. In summary, Enhanced platelet aggregation and increased release of serotonin occur shortly after the induction of diabetes by streptozocin in adult rats. These platelet changes precede alterations of endothelial function, as determined by plasma VIIIR:WF and VIIIR:Ag levels. Platelet changes respond more rapidly to insulin therapy than do endothelial changes in diabetic rats. The duration of diabetes before insulin therapy does not affect these relationships.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of insulin treatment in streptozocin-induced diabetic rats on in vitro platelet function and plasma von Willebrand factor activity and factor VIII-related antigen. 392 83

Increased platelet reactivity has been suggested in the pathogenesis of both arteriosclerosis and diabetic microangiopathy. Therefore, platelet function and platelet enzyme activities were assessed in a large group of 357 diabetics (256 patients with IDDM, aged 16-49 and 101 patients with NIDDM, aged 50-78) and 163 matched controls, and related to photographically documented retinopathy (Rd) and to peripheral vascular disease (PVD) as well as to plasma levels of von Willebrand factor (VIII R:Ag) as an indicator of endothelial damage. Patients with IDDM had increased platelet aggregation (PA, expressed as microM ADP threshold concentration) before Rd was detectable in comparison to control subjects (P less than 0.01). PA was further increased in patients with advanced Rd (P less than 0.01), whereas 20 newly diagnosed diabetics with IDDM exhibited normal PA. Patients with minimal Rd did not differ from patients without Rd. Plasma beta-thromboglobulin (reflecting platelet consumption in vivo) was enhanced significantly in patients with Rd only (P less than 0.05), as was malondialdehyde (MDA) production of platelets (as a measure of platelet endoperoxide formation). Factor VIII-related antigen in plasma was already increased in patients without Rd (P less than 0.05), yet more so in patients with Rd (P less than 0.01). Prostacyclin-stimulated adenylate cyclase activity (ACA) of platelets (as an antiaggregatory enzyme system) was twice as high in diabetics with advanced Rd compared with patients without Rd and with controls (P less than 0.01). Significant correlations were found between PA and plasma F VIII R: Hg, MDA production, and ACA of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1983 May
PMID:Platelet enzyme activities in diabetes mellitus in relation to endothelial damage. 608 25

We have measured plasma von Willebrand factor (VWF) as the factor VIII-related antigen, plasma fibronectin, and two of the serum somatomedins, insulin-like growth factor I (IGF I) and IGF II, in 51 diabetic patients and 25 nondiabetic control subjects. VWF was significantly higher in the diabetic group than in the controls (173 +/- 9% SEM versus 101 +/- 9%, P less than 0.001), as has been reported by others. However, within the diabetic group there was no significant difference in VWF between those patients without retinopathy, those with background or proliferative retinopathy, or those with macular edema. There was also no difference in VWF between the diabetic subjects with and those without proteinuria. These results rule against a previously advanced hypothesis that the increase in VWF in patients with diabetes is secondary to microangiopathy. No significant difference was observed in fibronectin, IGF I, or IGF II between the diabetic and control groups, between the diabetic group without retinopathy and the retinopathic subgroups, and between the diabetic subjects with and without proteinuria. In the diabetic patients, there was no correlation between diabetic control as assessed by glycosylated hemoglobin and glycosylated serum protein, and the plasma levels of VWF, fibronectin, IGF I, or IGF II. The results of this study strongly suggest that neither plasma VWF, fibronectin, IGF I, nor IGF II plays an important primary role in the pathogenesis of diabetic microvascular disease, although one or more of these factors might play a permissive role.
Diabetes 1984 Feb
PMID:Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy. 636 66

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

New concepts about the pathogenesis of atherosclerosis in diabetes mellitus are presented. Emphasis is given to alterations of endothelial function, as indicated by von Willebrand factor activity, prostacyclin release, and fibrinolytic activity in diabetes mellitus. Previous work on platelet aggregation and arachidonic acid metabolism is updated and recent findings are emphasized. The atherogenic mix of elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels in uncontrolled diabetes mellitus is noted. The lipid hypothesis is extended by consideration of very low-density lipoprotein and intermediate-density lipoprotein metabolism in diabetes. Lipoprotein-cell interactions that may contribute to atherosclerosis are reviewed and suggestions are made for future research in order to clarify the pathogenesis of atherosclerosis in diabetes mellitus.
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PMID:New concepts about the pathogenesis of atherosclerosis in diabetes mellitus. 642 41

The effects of standardized venous occlusion (VO) on factor VIII-von Willebrand factor (F VIII-VWF) components (F VIII:C, F VIIIR:AG, F VIIIR:RCof) and on fibrinolytic activity were investigated in 45 healthy subjects, in 28 women on oral contraceptives, and in 78 patients with various chronic diseases (28 with peripheral arterial disease, 19 with liver cirrhosis, 13 with rheumatoid arthritis, and 18 with diabetes). All the three F VIII-VWF components showed highly significant increases, although not of the same magnitude, with consequent variations in the ratios between them. A significant activation of fibrinolysis was also demonstrated with both euglobulin lysis time (ELT) and diluted blood clot lysis time (DBCLT). A strong linear correlation between pre- and post-stasis values was recorded for all the F VIII-VWF components and for the two fibrinolysis tests. No significant relationship was, on the contrary, found between F VIII-VWF and fibrinolytic parameters.
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PMID:Correlation between changes induced by venous occlusion on factor VIII-von Willebrand factor components and fibrinolytic activity. 642 15

Plasma von Willebrand factor was studied for quantitative and qualitative assessment in basal conditions and after release from the endothelium, as elicited by venous stasis of the forearm, in 8 healthy subjects and 8 patients with diabetic microangiopathy. von Willebrand factor was measured as factor VIII-related antigen (VIII R:Ag) and ristocetin co-factor (VIII R:Co). Its molecular size distribution was evaluated by bidimensional immunoelectrophoresis. The patients had higher basal levels of VIII R:Ag (171 +/- 45% vs 64 +/- 11% of plasma pooled from 20 healthy donors, p less than 0.05) and VIII R:Co (144 +/- 11% vs 88 +/- 8%, p less than 0.01). After stasis, both moieties increased significantly in the 2 groups, remaining higher in the patients (VIII R:Ag = 292 +/- 74% vs 89 +/- 18%, p = 0.01; VIII R:Co = 216 +/- 25% vs 116 +/- 10%, p less than 0.01). No differences in the molecular size distribution were observed between patients and controls, nor within the 2 groups before and after stasis. It is concluded that, in diabetic microangiopathy, the endothelial cells synthesize and store increased amounts of structurally normal von Willebrand factor.
Diabetes Res 1984 Nov
PMID:Quantitative and qualitative assessment of plasma von Willebrand factor variations, as induced by forearm venous stasis in patients with diabetic microangiopathy. 644 28

The high incidence of thrombosis in inflammatory states and previous reports of increased adhesion of erythrocytes to endothelial cells in diabetes mellitus and sickle cell anemia prompted us to study the effect of fibrinogen and fibronectin on erythrocyte-endothelial interactions. Purified human fibrinogen enhanced erythrocyte adhesion in a concentration-dependent fashion. Erythrocytes from normal subjects, diabetics, and patients with sickle cell anemia were studied. The ratio between the adhesion of normal red cells in a 4 gm/L fibrinogen to adhesion in buffer without fibrinogen was 3.6 (p less than 0.001). Fibronectin also increased red cell adhesion but the effect was less than that of fibrinogen. The addition of fibronectin to fibrinogen limited the enhancing effect of fibrinogen, although the effect of the mixture was greater than that of fibronectin alone (p less than 0.05). Anti-von Willebrand factor and antifibronectin, which react with endothelial cells, also produced an increase in erythrocyte adhesion. The potentiation of adhesion by fibrinogen was also seen in experiments using red cells from patients with sickle cell anemia or diabetes mellitus. These observations provide possible mechanisms for the involvement of plasma proteins in vascular occlusive diseases.
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PMID:Fibrinogen, a modulator of erythrocyte adhesion to vascular endothelium. 685 27

High levels of von Willebrand factor (vWF) have been reported in diabetics with vascular complications, suggesting a role for this protein in the development of cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM). Recently, a diet rich in monounsaturated fatty acids (MUFA) has been found to improve glycemic control and decrease diurnal blood pressure as compared with a high-carbohydrate (H-CHO) diet in NIDDM subjects. To study the impact of MUFA on the hemostatic system, we compared the levels of vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin before and after 3 weeks on a high-MUFA (H-MUFA) diet and on an isocaloric H-CHO diet in 15 NIDDM subjects. In a crossover study, the patients were randomly assigned to a H-CHO diet (50% carbohydrate, 30% fat [10% MUFA]) or a H-MUFA diet (30% carbohydrate, 50% fat [30% MUFA]). Before and on the last day of the two diets, vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin levels were measured. The H-MUFA diet caused a decrease in vWF from 1.31 +/- 0.08 to 1.13 +/- 0.08 U/mL (P < .004), whereas an unchanged level was observed after a H-CHO diet (1.19 +/- 0.11 v 1.25 +/- 0.11 U/mL, NS). The relative changes in vWF during 3 weeks on a H-MUFA and on a H-CHO diet attained -12.5% +/- 3.2% versus 5.7% +/- 3.5%, respectively (P < .0001). Furthermore, unchanged levels of fibrinogen, fibronectin, and alpha 2-macroglobulin were seen after usage of the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in non-insulin-dependent diabetic subjects. 752 26


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