Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.
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PMID:Enhancement of spontaneous fibrinolytic activity in diabetic retinopathy. 144 70

Parameters of fibrinolysis, including euglobulin fibrinolytic activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PA-inhibitor) activity, and plasmin-alpha 2-antiplasmin complex (PAP) were studied in 62 patients (35 women and 27 men; ages 53 +/- 16 years) with either insulin-dependent (IDDM) or noninsulin-dependent (NIDDM) diabetes mellitus. Compared to a control group of similar age (n = 57), the diabetic patients had a significantly lower mean euglobulin fibrinolytic activity (1.2 +/- 0.7 vs. 1.7 +/- 1.1 ng/ml, p less than 0.01) but significantly higher mean t-PA antigen (15.7 +/- 8.4 vs. 6.6 +/- 2.9 ng/ml, p less than 0.001) and PA-inhibitor activity (2.6 +/- 1.3 vs. 1.5 +/- 0.7 IU/ml, p less than 0.001) levels. Significant univariate correlations were observed between PA-inhibitor activity and age (r = 0.32, p less than 0.05), diastolic blood pressure (r = 0.42, p less than 0.01) and euglobulin fibrinolytic activity (r = -0.40, p less than 0.01). In multivariate analysis, only body mass index (positively) and euglobulin fibrinolytic activity (negatively) remained significantly related to PA-inhibitor activity in the total diabetic population as well as in the NIDDM group. The only parameter in the IDDM group significantly related to PA-inhibitor activity was diastolic blood pressure. These results suggest that PA-inhibitor plays a role in the regulation of fibrinolysis in diabetes patients and that factors like obesity and hypertension may be related to reduced fibrinolysis via PA-inhibitor levels.
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PMID:Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. 244 56

In cross-sectional studies elevations in growth hormone (GH), factor VIII related antigen (VIIIR:Ag), and plasminogen activator activity (PAA) have been connected with diabetic retinopathy. To evaluate the importance of these factors for the development of retinopathy, we have carried out a prospective study. In a primary study GH, VIIIR:Ag, and PAA were evaluated during a 25 min exercise test in 22 insulin dependent diabetes mellitus (IDDM) patients. After 5-7 years, the patients were re-evaluated and the presence of retinopathy in the follow-up study was correlated to the findings in the primary study. Patients with retinopathy in the primary or the second study (n = 14) showed a significant increase in GH (p less than 0.05) during the first 5 min of exercise compared with patients without retinopathy. Moreover, the 14 retinopathy patients showed further significant elevations in GH (p less than 0.001), VIIIR:Ag (p less than 0.01) and PAA (p less than 0.001) during the remaining 20 min of exercise. In contrast, patients without retinopathy (n = 8) in the follow-up study, did not show significant elevations in GH, VIIIR:Ag, and PAA during exercise. A lack of rise in GH, VIIIR:Ag, and PAA during exercise seems to indicate a resistance to retinopathy in IDDM patients.
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PMID:Absent elevations in growth hormone, factor VIII related antigen, and plasminogen activator activity during exercise in diabetic patients resistant to retinopathy. 313 76

Incubation of washed platelets in Tyrode buffer, pH 7.5, with insulin (200 microU/ml) and CaCl2 (1.2 mM) at 37 degrees C for 3 h resulted in a threefold increase of plasminogen activator activity in the supernatant over the basal level as determined by both the amidolytic assay and the proteolysis of alpha-casein through the formation of plasmin from plasminogen. This plasminogen activator showed no plasmin-like activity and was inhibited by anti-tissue plasminogen activator antibody as well as by type 1 plasminogen activator inhibitor. The substrate specificity and the inhibition of the enzymic activity by various inhibitors indicated that the platelet plasminogen activator (pPA) was related to tissue-type plasminogen activator of relative molecular weight 56,000. Fibrinolytic activity of pPA and its insulin-dependent release were demonstrated by the shortening of euglobulin lysis time and by the clot lysis time of platelet-rich plasma from normal and type I diabetes mellitus patients. Treatment of platelet membranes with insulin also increased the release of pPA. Increased levels of adenosine 3',5'-cyclic monophosphate (cAMP) in platelets by incubation with various agents completely inhibited the insulin-induced release of the activator. On the other hand, inhibition of platelet aggregation by aspirin had no effect on the release of pPA, indicating that the effect of cAMP was not due to the inhibition of platelet aggregation by the nucleotide.
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PMID:Insulin-induced release of plasminogen activator from human blood platelets. 753 Sep 14

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were studied in 18 smokers and 18 closely matched non-smokers, all of whom had Type 1 diabetes mellitus (DM). None of the patients had advanced complications of diabetes. The t-PA and PAI-1 antigen levels were measured in plasma before and after venous occlusion, and were normal in Type 1 diabetes regardless of smoking status. Platelet PAI-1 levels were also measured and were found to be normal both in smokers and non-smokers. In smokers with Type 1 DM, plasma PAI-1 was significantly correlated with triglycerides. The normal fibrinolytic potential found in smokers with diabetes contrasts starkly with the significantly elevated plasma PAI-1 reported in smokers without diabetes. In smokers, triglycerides may effect low levels of PAI-1 release into plasma; this process may be significantly augmented in the presence of smoking-induced insulin resistance. The lack of endogenous insulin release in Type 1 diabetes may obviate the characteristic rise in plasma PAI-1 found in smokers who do not have diabetes.
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PMID:Does chronic smoking influence fibrinolytic potential in type 1 diabetes mellitus? 970 73

Helicobacter pylori has been implicated in the cardiovascular risk of diabetic patients. The aim of our study was to investigate whether the Helicobacter pylori infection plays a role in the lipid and haemostasis patterns of type 1 diabetic patients. Twenty nine patients with type 1 diabetes mellitus and H. pylori infection were enrolled (Chlamydia pneumoniae negative). The H. pylori infection status was assessed by serology and urease breath test. In all patients levels of total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, lipoprotein (a) (Lpa) C reactive protein (CRP), fibrinogen, thrombin/antithrombin III complex (TAT), plasminogen activator inhibitor type 1(PAI-1), tissue plasminogen activator (t-PA) and von Willebrand antigen were measured. All patients were evaluated before and after H. pylori eradicating treatment with amoxicillin, clarithromycin and omeprazole. Twenty two patients were eradicated and seven remained infected. In H. pylori eradicated patients, HDL cholesterol increased (59.7+/-18.9 mg/dl vs 65.2+/-15. 9 mg/dl, P << 0.05), after treatment. After H. pylori eradication, the levels of CRP and TAT decreased (48+/-0.7 ng/l vs 3.3+/-0.4 ng/l;P << 0.05), (27.7+/-44.7 microg/ml vs 2.1+/-1.4 microg/ml, P << 0.05), respectively. The decrease in TAT was higher in the group of H. pylori (+) patients with higher levels of TAT (TAT >> 20 ng/ml, 92.8+/-41.6 ng/ml vs 1.9+/-2.0 ng/ml, P << 0.005; TAT 4Eth 20 ng/ml; 10.1+/-5.2 ng/ml vs 2.2+/-0.6 ng/ml, P << 0.05). These changes did not occur in patients without H. pylori eradication. Eradication of H. pylori infection in type 1 diabetic patients modifies some parameters of lipid and haemostasis patterns, (increase of HDL-cholesterol, reduction of Lpa and decrease of CRP and TAT) and so contributes to improvement of cardiovascular risk factors in these patients.
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PMID:Improvement in lipid and haemostasis patterns after Helicobacter pylori infection eradication in type 1 diabetic patients. 1057 22

Several haemostatic abnormalities are associated with proliferative diabetic retinopathy. While abnormalities in plasma fibrinolytic activity have been described in diabetic retinopathy, platelets (a rich source of plasminogen activator inhibitor type 1, PAI-1) have received little attention. As a result, little is known about the fibrinolytic potential of circulating whole blood in diabetic retinopathy. The concentrations of tissue-type plasminogen activator (t-PA) and of its fast-acting inhibitor. PAI-1 were measured in plasma from eight patients with type 1 diabetes complicated by proliferative retinopathy, and from eight patients with type 1 diabetes and background or no retinopathy, matched for age, sex and duration of diabetes. The concentration of PAI-1 in platelets was also measured. The ratio of t-PTA to PAI-1 in plasma was significantly higher in patients with proliferative retinopathy than in those without (0.66 vs. 0.37, p < 0.02). The average quantity of PAI-1 per platelet was significantly lower in the group with proliferative retinopathy (0.33 vs. 0.50 ng/10(6) platelets, p < 0.02). These data suggest that among patients with type 1 diabetes, total circulating fibrinolytic potential is higher in those with proliferative retinopathy.
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PMID:Circulating tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in proliferative diabetic retinopathy: a pilot study. 1066 20

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.
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PMID:Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus. 1189 23

Endothelial dysfunction is defined as the loss of endothelium properties, e.g. alteration of protein synthesis, increased vascular tone and permeability, acquisition of prothrombotic and antifibrinolytic properties. Endothelium, a primary target of unbalanced glycaemic control, is involved in the pathogenesis of vascular complications in patients with type 1 diabetes mellitus (DM). Vascular endothelium damage is characterised by an increase of endothelium-derived regulatory proteins. vWF and t-PA may be useful to investigate early endothelium involvement. However, impaired endothelium-dependent vasodilatation may be a more sensitive marker. Abnormal markers of endothelial cell activation and impaired endothelium-dependent vasodilatation have been observed in young patients with type I DM. Hyperglycaemia may alter normal endothelium functions, either directly or indirectly, by inducing different metabolic pathways. Complete understanding of the pathophysiology of endothelial dysfunction may lead to timely therapeutic intervention to prevent its development and to slow the progression of diabetic complications.
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PMID:Endothelial dysfunction in children with type 1 diabetes mellitus. 1200 80

Given the paucity of data in type 1 diabetes concerning lipoprotein-associated phospholipase A( 2) (Lp-PLA(2)), we examined its prospective relationship with coronary artery disease (CAD), as well as the effect of modification by C-reactive protein (CRP) and haptoglobin genotype, in individuals with type 1 diabetes who are at an increased risk for CAD due to also having macroalbuminuria (n=96). Although Lp-PLA(2) activity was univariately predictive of CAD (HR=1.54 per SD, p=0.009), this relationship was not significant after covariate adjustment (p=0.59). There was a significant interaction between Lp-PLA(2) and CRP (p=0.02), i.e. those with both markers greater than the median level were more likely to have a CAD event than those persons with low levels of both (HR=2.89, p=0.06). When stratified by haptoglobin genotype, Lp-PLA(2) was predictive of CAD in persons with the 2/1 (HR=2.40, p=0.05), but not 2/2 (HR=0.66, p=0.27), genotype. The association between Lp-PLA(2) activity and CAD differs by CRP and haptoglobin genotype in this group of persons with type 1 diabetes and macroalbuminuria.
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PMID:Lipoprotein-associated phospholipase A2, C-reactive protein, and coronary artery disease in individuals with type 1 diabetes and macroalbuminuria. 2036 32


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