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)

Nonenzymatic glycation of antithrombin III has been reported to cause the reduction of heparin-catalyzed thrombin-inhibiting activity in diabetes. The effect of in vitro nonenzymatic glycation of pure antithrombin III on heparin binding and heparin-potentiated activity under a variety of buffers and pH values was studied to further clarify the physiological significance of this reaction. The extent of glycation, measured by the fructosamine assay and [14C]glucose binding, was enhanced by the presence of phosphate ion (pH 7.45, 8.5 and 9.5) and increased linearly with increasing phosphate ion concentration from 0.01 to 0.2 M phosphate. Conversely, the heparin-catalyzed antithrombin activity decreased from 93.1% of controls for 0.01 M phosphate to 73.5% for 0.2 M phosphate as the extent of glycation increased. The increase in intrinsic fluorescence induced by binding of heparin to antithrombin III was also moderated by glycation of antithrombin III in a dose-dependent manner with a negative correlation coefficient of -0.94. Direct measurement of the heparin binding by affinity chromatography showed a decrease in the heparin-binding fraction which correlated with the degree of glycation and the decrease in heparin-catalyzed activity. These studies suggest that nonenzymatic glycation may be responsible for the reduction in antithrombin III activity observed in some diabetics.
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PMID:Phosphate promotes glycation of antithrombin III which interferes with heparin binding. 259 94

Levels of factors II, V, VII, VIII C, VIII R:Ag, VIII vW, IX, X, PT, PTT, TT, TR, antithrombin III and fibrinogen were evaluated in 11 children with insulin-dependent diabetes mellitus (IDDM) at onset of disease and after 3 months and in 15 healthy age-matched controls. At onset of IDDM a significant increase was observed only in mean values of factor VIII C, VIII R:Ag and in VIII vW. After 3 months the levels of factor VIII C returned within the normal range whilst no variations of factor VIII R:Ag and vW were found. These data show that coagulation abnormalities are already present at onset of IDDM and that endothelial damage evidenced by high values of factor VIII R:Ag and vW may persist even in a phase of good metabolic control. Levels of factor VIII C seem to be related to the increased protein glycosylation of IDDM.
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PMID:[Blood coagulation parameters in insulin-dependent diabetic children at onset of the disease and after 3 months]. 266 14

We compared concentrations of antithrombin III (AT-III) in plasma, as determined by an immunological method and by a functional thrombin inhibition method, in the presence of heparin in 160 blood samples from Type I diabetics. Although the correlation was highly significant (P less than 0.001) between the results obtained by the two methods, our data demonstrated that results by the thrombin inhibition assay, 121 (SD 15)%, expressed as percentages of the results for a normal plasma pool, were significantly (P less than 0.001) higher than by the immunoreactive method, 104 (SD 15)%, indicating an overestimation of functionally active AT-III. Concentrations of functionally active AT-III determined by a factor Xa inhibition assay, 105 (SD 13)%, were in the same range as immunoreactive AT-III. Addition of IgG antiserum to normal pooled plasma quenched only about 90% of the AT-III activity determined by the thrombin inhibition assay, but all of the AT-III activity determined by a factor Xa inhibition assay. These results demonstrate that the factor Xa inhibition assay is more specific for the determination of AT-III than the thrombin inhibition assay. We suggest that the high concentrations of heparin cofactor II, 117 (SD 17)%, might have caused an overestimation of AT III in this group of patients with diabetes Type I, and should not be overlooked in other clinical situations.
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PMID:Increased concentrations of heparin cofactor II in diabetic patients, and possible effects on thrombin inhibition assay of antithrombin III. 291 May 81

Twenty type II (non-insulin-dependent) poorly controlled diabetics had tests of coagulation and platelet function performed while receiving high-dose sulphonylurea therapy and at 1 and 3 months following their conversion to insulin. Although no overall change in glycaemic control (assessed by glycosylated haemoglobin) was noted, a reduction in thrombin generation was observed, as judged by a significant fall in fibrinopeptide A concentrations. No changes in factor VIII coagulant activity (VIII:C), factor VIII-related antigen or antithrombin III were found. Glycosylated haemoglobin concentrations showed significant correlations with antithrombin III and factor VIII:C, suggesting that improved glycaemic control might lead to an improvement of antithrombin III function and lower factor VIII:C concentrations. No changes in platelet function were detected. The introduction of an insulin regimen that improves glycaemic control might lead to a reversal of the 'hypercoagulable state' found in type II diabetes.
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PMID:Effect of insulin therapy on coagulation and platelet function in type II (non-insulin-dependent) diabetes mellitus. 310 3

Theories of intimal injury leading to plaque formation include platelet adhesion and production of growth factors, hypercholesterolemia, smooth muscle cell proliferation, macrophage activity, defective utilization of low-density lipoproteins via deficient receptors, and deficiency in cellular lysosomal enzymes. High levels of low-density lipoproteins and intermediate-density lipoproteins, as well as their apoproteins, are strong risk factors for cardiovascular disease. The lowering of the cholesterol level has been shown to produce significant regression of atherosclerotic lesions. Data also suggest an interaction between lipids and platelets, although the role of coagulation disorders as an independent risk factor for atherosclerosis is difficult to assess. Although much of the data are controversial, there is evidence that platelet survival time is a strong predictor of severe vessel damage. In addition, some studies have reported decreased activity of antithrombin III with coronary artery disease, and there appears to be a direct correlation between fibrinogen and cholesterol levels. Finally, diabetes mellitus (both types I and II) is a significant independent risk factor for atherosclerosis. The risk is not related to the severity or duration of diabetes, and it appears to be greater in women than in men.
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PMID:Lipids, clotting factors, and diabetes: endogenous risk factors for cardiovascular disease. 328 30

The side effects and health risks associated with contraceptive pills have been explained by the metabolic changes they produce. The steroids in them affect the metabolism of hormones, vitamins, trace elements, carbohydrates, proteins and lipids. The changes, however, are minimal, and the steroid content has decreased over the years. The liver toxicity of currently used pills is small. Serum amino transferase values need to be checked once during the 1st 3-6 months of use, although routine liver tests have been halted. Contraceptive pills cause fluid retention and weight increase because of the estrogens. Progestin increases the secretion of water and natrium. Osteoporosis, however, does not develop. Contraceptive pills do not cause diabetes, although blood sugar increases more than average during the glucose tolerance test. Some progestins have a poor anabolic effect. The ethinylestradiol pill increases the content of some liver-based proteins in the circulation. Smoking is an important risk factor because it increases changes in the content of coagulation factors and antithrombin III. The progestin component determines the effect of the pill on lipoproteins. Changes in the cholesterol and triglycerides have remained minimal, as the estrogen-progestin content of the pill has been decreased. A new product that acts antiandrogenically has been developed for contraception by those suffering from acne.
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PMID:[Metabolic effects of contraceptive pills]. 333 Nov 41

The effect of nonenzymatic glycosylation on the kinetics and structure-function relationships of antithrombin III were investigated at normal physiologic concentrations of antithrombin III and glucose, which are 5.2 microM and 5 mM, respectively. The results were compared with antithrombin III incubated at the glucose concentration expected to be found in severely diabetic patients (15 mM). Antithrombin III incubated at 5 mM lost 33% of the heparin cofactor activity after 7 days, whereas antithrombin III incubated at 15 mM lost 50% for the same period. Under both conditions, half of the heparin cofactor activity was lost after 15 days. When D-[U-14C]glucose was used as tracer, approximately 0.6 mol glucose/mol protein was incorporated after 10 days at both concentrations of glucose. A detailed evaluation of the kinetics of inhibition of thrombin by glycosylated antithrombin III revealed that the second-order rate constant is three times smaller than that of normal antithrombin III. On the basis of these data, it is concluded that glycosylated antithrombin III with 50% depressed heparin cofactor activity is three times weaker than normal antithrombin III as an inhibitor of thrombin. The implications of these observations with respect to the possible pathogenesis of thrombosis in diabetes are discussed.
Diabetes 1988 Aug
PMID:Demonstration of altered antithrombin III activity due to nonenzymatic glycosylation at glucose concentration expected to be encountered in severely diabetic patients. 339 45

Alterations of plasma coagulation factors have been reported in diabetic patients with severe microangiopathy and metabolic derangement. No information is available, however, for well-controlled type-I diabetic patients. Thus, we studied coagulation factors of the contact phase and inhibitors in 80 fairly well-controlled diabetics (42 female, 38 male, age 28 +/- 11 SD years). Mean HbA1c in these patients was 6.6 +/- 1.0 SD, duration of diabetes ranged from 6 months to 30 years, and 36% had retinopathy shown by fluorescein angiography. The well-controlled diabetic patients did not differ from controls in terms of the activity of prekallikrein, factor XII, high molecular weight kininogen, kallikrein inhibitor, C-1-esterase inhibitor and antithrombin III. Only alpha-2-macroglobulin, an inhibitor of the contact phase of blood coagulation, was elevated significantly in these patients (p less than 0.05). Diabetics with retinopathy had similar activities of prekallikrein, factor XII, high molecular weight kininogen, kallikrein inhibitor, c-1-esterase inhibitor and antithrombin III when compared with patients without retinopathy and controls respectively. alpha-2-macroglobulin did not differ in patients with and without diabetic retinopathy but were significantly elevated in both groups compared with controls. Correlation analysis showed significant positive correlation between HbA1c and the activity of high molecular weight kininogen, kallikrein inhibitor and alpha-2-macroglobulin. In patients with poor metabolic control (n = 11; 6 female, 5 male; age 25 +/- 5 SD years; HbA1C 10.7 +/- 0.9) prekallikrein (p less than 0.05), kallikrein inhibitor (p less than 0.005) and alpha-2-macroglobulin (p less than 0.005) were significantly elevated compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1988 Apr
PMID:Coagulation factors of contact phase of haemostasis are normal in well-controlled type-I diabetic patients despite presence of diabetic retinopathy. 340 69

Thirty vasculopathic subjects with hyperlipoproteinemia (18) and/or diabetes (22) underwent a clinical double-blind study in order to evaluate the effect of sulodexide on lipid and hemorheologic parameters. The experimental design consisted of a first 20-day i.m. therapeutic period with either sulodexide (300 Lipasemic Units twice daily via intramuscular route) or placebo and the following 70 days with the active compound for both groups at the same posology. Results obtained demonstrated that sulodexide yields a hypotriglyceridemic effect on type IV hyperlipoproteinemia and hypofibrinogenic effect, as well. Moreover, this compound exerted a beneficial effect on HDL Cholesterol levels and on the antithrombin III activity by increasing both parameters significantly. Signs and symptoms were alleviated, particularly in the most severe cases of peripheral vascular disease. Insignificant and slight changes were observed at the end of treatments as regards the efficacy of the two administration routes, the i.m. one being more efficacious on lipid parameters and faster acting. No side effects or intolerance were observed during the different periods of the trial.
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PMID:The use of sulodexide in the treatment of peripheral vasculopathy accompanying metabolic diseases. Controlled study in hyperlipidemic and diabetic subjects. 351 14

The effect of rapid daily variation of glycemia and labile HbA1 on both antithrombin III (ATIII) activity and plasma concentration in ten insulin dependent diabetics has been evaluated. The variations of both plasma glucose and labile HbA1 were inversely correlated to the alterations of ATIII activity (r = -0.71 and r = -0.73, respectively, p less than 0.001), while no change in ATIII plasma concentration was present. These data suggest a direct role of glucose in determining rapid alteration of ATIII biologic activity, in vivo, in diabetes, probably mediated by labile non-enzymatic glycation.
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PMID:Daily rapid blood glucose variations may condition antithrombin III biologic activity but not its plasma concentration in insulin-dependent diabetes. A possible role for labile non-enzymatic glycation. 356 29


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