Insulin Resistance Is Associated with Increased Circulating Level of Thrombin-Activatable Fibrinolysis Inhibitor in Type 2 Diabetic Patients

Hori, Yasuko; Gabazza, Esteban C.; Yano, Y; Katsuki, Akira; Suzuki, Koji; Adachi, Yukihiko; Sumida, Yasuhiro

doi:10.1210/jcem.87.2.8214

Cited by 92 publications

(79 citation statements)

References 26 publications

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“…Elevated plasma levels of TAFI are associated with increased risk of cardiovascular diseases [116–120]. In diabetes, TAFI levels appear to correlate with HbA1c, indicating an association between TAFI levels and poor glycaemic control [121]. Plasma concentration and activity of TAFI are significantly increased in T2DM patients compared with healthy controls, particularly in obese patients [121].…”

Section: Mechanisms Of Hypofibrinolysismentioning

confidence: 99%

“…In diabetes, TAFI levels appear to correlate with HbA1c, indicating an association between TAFI levels and poor glycaemic control [121]. Plasma concentration and activity of TAFI are significantly increased in T2DM patients compared with healthy controls, particularly in obese patients [121]. TAFI levels have also been linked in T2DM to the presence of microvascular complications manifesting as microalbuminuria [122, 123].…”

Section: Mechanisms Of Hypofibrinolysismentioning

confidence: 99%

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Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

Kearney

Tomlinson

Smith

et al. 2017

Cardiovasc Diabetol

106

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An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition.

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Section: Mechanisms Of Hypofibrinolysismentioning

confidence: 99%

Section: Mechanisms Of Hypofibrinolysismentioning

confidence: 99%

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

Kearney

Tomlinson

Smith

et al. 2017

Cardiovasc Diabetol

106

View full text Add to dashboard Cite

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“…The latter were investigated in diabetes type 1 and 2, but less is known about them in GDM. Hori et al [20] demonstrated that the plasma concentration and activity of TAFI were significantly higher in patients with type 2 diabetes than in healthy controls [20]. Moreover, they showed that the plasma TAFI levels were independently and significantly correlated with glucose intolerance (HbA 1c ), and with obesity (BMI, visceral fat area) [20].…”

Section: Discussionmentioning

confidence: 99%

“…Hori et al [20] demonstrated that the plasma concentration and activity of TAFI were significantly higher in patients with type 2 diabetes than in healthy controls [20]. Moreover, they showed that the plasma TAFI levels were independently and significantly correlated with glucose intolerance (HbA 1c ), and with obesity (BMI, visceral fat area) [20]. Among patients with type-1 diabetes although Antovich et al [21] reported a decrease in TAFI antigen levels, Harmanci et al [22] did not find any alterations in TAFI antigen levels.…”

Section: Discussionmentioning

confidence: 99%

Levels of thrombin activatable fibrinolysis inhibitor in gestational diabetes mellitus

Gümüş

Kargılı²,

Karakurt³

et al. 2013

Gynecological Endocrinology

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Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase, which is synthesised in liver and activated by thrombin and the thrombin-thrombomodulin complex. TAFI suppresses fibrinolysis by removing carboxy-terminal lysine residues from partially degraded fibrin. In this study we aimed to assess the circulating levels of TAFI antigen, 'a fibrinolytic parameter' in women with gestational diabetes (GDM). Thirty-four pregnant women with GDM and 50 pregnant women with normal glucose tolerance were included in the study. Plasma TAFI antigen levels were significantly higher in pregnant women with GDM when compared with controls. Increased TAFI levels may contribute to the decreased fibrinolytic potency, causing a thrombophilic state. GDM is regarded as a specific form of diabetes, and it could in addition be a predictor of type 2 diabetes mellitus in the future and the risk of complications due to hypercoagulability increases in this disease. Increased TAFI levels may also have a role in increased risk of hypercoagulability.

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“…Both the level and the activity of plasma TAFI in patients with T2DM are reported to be significantly higher than those in healthy individuals [2]. Both the level and the activity of plasma TAFI in patients with T2DM are reported to be significantly higher than those in healthy individuals [2].…”

Section: Introductionmentioning

confidence: 95%

Effect of single nucleotide polymorphism in thrombin-activatable fibrinolysis inhibitor on the risk of diabetic macrovascular disease

Zheng

Chen

et al. 2015

Blood Coagulation &Amp; Fibrinolysis

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Hypofibrinolysis is commonly found in patients with diabetes mellitus and is associated with the increased risk for many diabetic complications. An important inhibitor of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), participates in hypofibrinolysis in diabetes mellitus and may be involved in diabetic macrovascular disease. The present study was designed to determine whether TAFI polymorphisms (505G/A and 1040C/T) and TAFI levels are correlated with the development of type 2 diabetes mellitus (T2DM) and macrovascular diseases (MVDs). A total of 249 clinical samples were collected, including 102 healthy individuals (H group), 44 T2DM patients without MVD (T group) and 103 T2DM patients with MVD (M group). The 505G/A polymorphism was equally represented in the three groups. In contrast, analysis of the 1040C/T polymorphism revealed a statistically lower percentage of the T allele in the M group than in the H group (P = 0.014). This difference was due to decreased T/T homozygotes in the M groups compared with the H group (P = 0.029). The antigen TAFI level was 31.72 ± 13.64% in the H group, 62.56 ± 18.77% in the T group (P < 0.05, compared with the H group) and 63.70 ± 15.76% in the M group (P < 0.05, compared with the H group). As high plasma TAFI level is associated with the increasing risk of T2DM, it may thus serve as a potential marker for the diagnosis of T2DM.

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Insulin Resistance Is Associated with Increased Circulating Level of Thrombin-Activatable Fibrinolysis Inhibitor in Type 2 Diabetic Patients

Cited by 92 publications

References 26 publications

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

Levels of thrombin activatable fibrinolysis inhibitor in gestational diabetes mellitus

Effect of single nucleotide polymorphism in thrombin-activatable fibrinolysis inhibitor on the risk of diabetic macrovascular disease

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