Induction and Possible Role of Fibrinolysis in Diabetes Mellitus

Gram, Jørgen Brodersen; Jespersen, Jørgen

doi:10.1055/s-2007-1002646

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…The contribution of fibrinolytic system abnormalities to the development of diabetic micro-and macrovascular complications is still controversial [15]. In several studies activity of the fibrinolytic system in diabetics was found to be increased [16][17][18], decreased [19][20][21] or unchanged [22].…”

Section: Introductionmentioning

confidence: 99%

Coagulation and Fibrinolysis Parameters in Type 2 Diabetic Patients with and without Diabetic Vascular Complications

Erem¹,

Hacıhasanoğlu²,

Çeli̇k³

et al. 2004

Med Princ Pract

100

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Objectives: To investigate the markers of endogenous coagulation/fibrinolysis and vascular endothelial cell function, and to assess the relationships between hemostatic parameters and diabetic vascular complications in type 2 diabetic patients. Materials and Methods: Coagulation and fibrinolysis parameters were measured in 92 type 2 diabetic patients (43 male, 49 female, mean age 50.1 ± 13.4 years) with (n = 44) and without (n = 48) vascular diabetic complications, and in 40 nondiabetic healthy subjects (20 male, 20 female, mean age 49.8 ± 15.1 years). Common lipid parameters were also measured. Results: The plasma levels of fibrinogen, antithrombin III (AT III), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) activity and prothrombin time were found to be significantly increased in the type 2 diabetic patients compared with the healthy subjects. Glycosylated hemoglobin lc was inversely correlated with plasma protein S and activated prothrombin time. Protein C and S activities were positively correlated with plasma vWF activity, and were negatively correlated with plasma t-PA levels. vWF activity was negatively correlated with plasma t-PA levels. AT III levels were positively correlated with plasma total cholesterol levels, plasma low density lipoprotein cholesterol levels, plasma triglycerides and D-dimer levels. Plasma PAI-1 levels and factor V activity in diabetic patients with microvascular complications were significantly higher than those of the diabetic patients without microvascular complications. The plasma PAI-1 and platelet count were increased in patients with diabetic retinopathy compared with the diabetic patients without retinopathy. Plasma PAI-1 levels and factor VII activity were significantly higher in the diabetic patients with nephropathy than in diabetic patients without nephropathy. Plasma concentrations of fibrinogen and PAI-1 were significantly higher in the diabetic patients with neuropathy than the diabetic patients without neuropathy. Conclusions: The data demonstrated that patients with type 2 diabetes mellitus had a hypercoagulable state and hypofibrinolysis, thereby indicating that activation of coagulation with a reduced fibrinolytic activity may contribute to the increased risk of vascular disease in type 2 diabetic patients.

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Section: Introductionmentioning

confidence: 99%

Coagulation and Fibrinolysis Parameters in Type 2 Diabetic Patients with and without Diabetic Vascular Complications

Erem¹,

Hacıhasanoğlu²,

Çeli̇k³

et al. 2004

Med Princ Pract

100

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“…Conversely, there is evidence that SU might increase tissue plasminogen activator production by endothelial cells and inhibit platelet function, two mechanisms that would likely prove to be beneficial at the acute stage of myocardial infarction [1,27].…”

Section: Representativeness Of the Study Populationmentioning

confidence: 99%

Role of previous treatment with sulfonylureas in diabetic patients with acute myocardial infarction: results from a nationwide French registry

Danchin

Charpentier²,

Ledru

et al. 2004

Diabetes Metab. Res. Rev.

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Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture

Pandolfi¹,

Iacoviello

Capani³

et al. 1996

Diabetologia

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Hyperglycaemia and hyperinsulinaemia have both been related to accelerated atherosclerosis in non-insulin-dependent diabetes mellitus (NIDDM). Plasma fibrinolytic potential is reduced in NIDDM and it is known that glucose and insulin can modulate plasminogen activator inhibitor (PAI-1) and tissue-plasminogen activator (t-PA) secretion and can therefore regulate local fibrinolysis. Vascular smooth muscle cells (vSMC) play an important role in the development of atherosclerotic lesions; however, the role of insulin and glucose in regulating PAI-1 and t-PA production in vSMC is presently not known. Therefore, we cultured arterial vSMC explanted from human umbilical cords and exposed them to increasing concentrations of glucose (5, 12, 20, 27, 35 mmol/l) or insulin (0.1, 0.5, 1, 10 nmol/l) in a serum free medium. After 24 h, PAI-1 and t-PA antigens and activity were evaluated in the culture medium; in cells exposed to 20 mmol/l glucose and to 0.5 nmol/l insulin PAI-1 gene expression was also evaluated. An increase in PAI-1 antigen was observed at each glucose concentration (by 138, 169, 251 and 357% as compared to 5 mmol/l glucose) which was paralleled by an increase in PAI-1 activity. t-PA concentration was also increased by glucose but its activity was sharply reduced. An increase in PAI-1 antigen was detected at each insulin level (by 121, 128, 156 and 300% as compared to no insulin). PAI-1 activity was slightly increased at the lowest insulin concentrations but markedly increased by 10 nmol/l insulin. t-PA antigen was also increased by insulin; however, its activity was markedly reduced at each concentration. As compared to control cells, PAI-1 mRNA was increased by 2.5 and 2.0 fold by 20 mmol/l glucose and 0.5 nmol/l insulin, respectively. We conclude that in human vSMC both glucose and insulin can affect the fibrinolytic balance so as to reduce fibrinolytic potential. This might contribute to decreased local fibrinolysis and thereby might accelerate the atherothrombotic process in NIDDM subjects.

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Induction and Possible Role of Fibrinolysis in Diabetes Mellitus

Cited by 5 publications

References 34 publications

Coagulation and Fibrinolysis Parameters in Type 2 Diabetic Patients with and without Diabetic Vascular Complications

Coagulation and Fibrinolysis Parameters in Type 2 Diabetic Patients with and without Diabetic Vascular Complications

Role of previous treatment with sulfonylureas in diabetic patients with acute myocardial infarction: results from a nationwide French registry

Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture

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