Thrombogenic factors are related to urinary albumin excretion rate in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients

Knöbl, Paul; Schernthaner, Gerit-Holger; Schnack, Ch.; Pietschmann, Péter; Griesmacher, Andrea; Prager, Rudolf; Müller, Mathias M.

doi:10.1007/bf02374497

Cited by 85 publications

(75 citation statements)

References 35 publications

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“…The plasma antigen levels of PC and of its cofactor PS were found to be either decreased or increased in various reports depending on the type of diabetes. While reduced plasma levels of PC antigen have been described in IDDM patients, they were found to be elevated in those with NIDDM [4,33]. Increased plasma levels of PC antigen were also observed in our NIDDM patients confirming these previous observations.…”

Section: Discussionsupporting

confidence: 91%

“…In addition, a poor anticoagulant response as judged by the decreased formation of APC-PCI complex and low values of TAR were observed in cases presenting microalbuminuria. Enhanced activation of the clotting system has been previously reported in patients with insulin-dependent diabetes (IDDM) or NIDDM [4]. High plasma concentrations of FM, prothrombin F1 + 2 and fibrinogen found in our NIDDM patients provide confirmatory evidence of these previous reports [26,27].…”

Section: Discussionsupporting

confidence: 91%

“…This activation of blood coagulation has been recently implicated as an important contributing factor for the occurrence of vascular complications in diabetes [28]. In large epidemiological studies the pro-coagulant factors, fibrinogen and factor VII, have been described to be independent predictors of cardiovascular events in diabetic and non-diabetic subjects, and the detection of microalbuminuria, another wellknown independent indicator of much greater risk of premature death from cardiovascular complications, has been demonstrated to correlate significantly with various haemostatic variables [4,29,30]. Accordingly, in the present study, the plasma levels of fibrinogen and prothrombin F1 + 2 were also found to be significantly higher in diabetic patients with microalbuminuria than in those with normoalbuminuria.…”

Section: Discussionmentioning

confidence: 99%

“…APC exerts anticoagulant activity by inactivating factors Va and VIIIa on the membrane of platelets and endothelial cells, and also by stimulating fibrinolysis in concert with protein S (PS) [3]. The biological activity of the anticoagulant PC pathway in diabetes remains controversial; although the plasma antigen levels of PC in diabetes have been previously reported, the degree of PC conversion to its active protease is unclear [4,5]. An assay for measuring levels of APC in complex with its main inhibitor, PC inhibitor or PCI (APC-PCI complex) has been recently developed [6].…”

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confidence: 99%

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Protein C activation in NIDDM patients

et al. 1996

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Alteration of the clotting system in diabetic patients is presently the focus of increasing interest due to its potential role in the pathogenesis of large and smallvessel disease in diabetes mellitus. It is believed that enhanced pro-coagulant activity is linked to the excessive cardiovascular morbidity and mortality among diabetic patients which have not been fully explained by major risk factors such as arterial hypertension, cigarette smoking and hypercholesterolaemia. Perturbance of haemostasis has also been implicated in the development of complications such as nephropathy and retinopathy and in the acceleration of atherogenesis observed in diabetic patients [1,2]. Diabetologia (1996Diabetologia ( ) 39: 1455Diabetologia ( -1461 Protein C activation in NIDDM patients Summary Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble Eselectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 ± 3.8 vs 3.0 ± 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 ± 2.6 vs 35.3 ± 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 ± 0.6 vs 8.6 ± 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 ± 2.9 vs 23.4 ± 2.6 %, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Protein C activation in NIDDM patients

et al. 1996

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“…9 Although diabetes is known to be associated with hypercoagulable states, the pathogenetic mechanism appears to involve platelet dysfunction rather than a disruption of clotting factor homeostasis. 4,[10][11][12][13][14][15][16][17][18] Other factors (e.g., comorbidity or concomitant medication) are therefore likely to contribute to this interaction.…”

mentioning

confidence: 99%

Impact of Age, CYP2C9 Genotype and Concomitant Medication on the Rate of Rise for Prothrombin Time During the First 30 Days of Warfarin Therapy

Wilke¹,

Berg²,

Vidaillet³

et al. 2005

Clinical Medicine & Research

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Objectives:To characterize the impact of several important clinical variables on the rate of anticoagulation during warfarin initiation (i.e., the first 30 days).Design: Retrospective study.Setting: An anticoagulation service of a large horizontally integrated, multispecialty group practice in central and northern Wisconsin. Participants:Patients with sufficient laboratory data obtained during the initiation phase of warfarin treatment. Methods:Patients were consented and genotyped for cytochrome P450 (CYP) 2C9 polymorphisms. Anticoagulation laboratory data were then electronically abstracted and fitted to a logistic growth model. Rate of anticoagulation was compared between groups.Results: During warfarin initiation, the mean slope for rise in International Normalized Ratio (INR) of prothrombin time was significantly associated with age (p=0.03, n=166). Because a relationship between diabetes and warfarin dosing has been suggested previously, we assessed the impact of this comorbidity in our model as well. Diabetes showed relatively little impact, but concomitant treatment with an anti-diabetic sulfonylurea medication was associated with an increase in slope (3-fold, p<0.05).

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Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: A prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus

Reverter

Tàssies

et al. 1997

Am. J. Hematol.

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Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin-dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirteen patients presented clinically detectable microangiopathy (8 retinopathy and 5 both retinopathy and microalbumin-uria). A cross-sectional study of lipid profile, coagulation parameters, and a flow-cytometric evaluation of tissue factor expression in normal monocytes induced by patient plasma were performed. Patients were re-evaluated for microangiopathy in a 3-year median follow-up. Patients showed triglyceride enrichment in low (P = 0.00002) and high density lipoproteins (P = 0.004) and increased levels of D-dimer (P < 0.00001), prothrom-bin fragment 1 + 2 (P < 0.00001), and thrombin-antithrombin III complex (P = 0.0001). Patients with clinically detectable microangiopathy had increased type 1 plasminogen activator inhibitor (P = 0.00001), thrombomodulin (P = 0.02), and induced monocyte tissue factor expression (P < 0.00001). Nine patients developed clinically detectable microangi-opathy in the follow-up and the only predictive variable was increased induced tissue factor expression. In conclusion, in these patients elevated thrombin and fibrin generation reflects a hypercoagulable state but clinically detectable microangiopathy seems related to endothelial cell injury markers and to increased induced tissue factor expression on monocytes. Am. J. Hematol. 56:93-99, 1997.

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Thrombogenic factors are related to urinary albumin excretion rate in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients

Cited by 85 publications

References 35 publications

Protein C activation in NIDDM patients

Protein C activation in NIDDM patients

Impact of Age, CYP2C9 Genotype and Concomitant Medication on the Rate of Rise for Prothrombin Time During the First 30 Days of Warfarin Therapy

Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: A prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus

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