Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat

Abstract

Decreased plasma fibrinolysis may contribute to accelerated atherothrombosis in diabetes. To observe whether hyperglycemia and hyperinsulinemia, common findings in type 2 diabetes, acutely affect plasma fibrinolysis in vivo, we evaluated plasma fibrinolysis (lysis of fibrin plates, free PAI-1 activity and t-PA activity) in the rat after a hyperglycemic euinsulinemic clamp (n=8), an euglycemic hyperinsulinemic clamp (n=7) or a saline infusion (n=15). Plasma fibrinolytic activity was sharply reduced after both the hyperglycemic and hyperinsulinemic clamps as compared to the respective controls (mean lysis areas on the fibrin plate, 139+/-21 vs. 323+/-30 mm2, p<0.001; 78+/-27 vs. 312+/-27 mm2 p<0.001, respectively). Plasma PAI-1 activity was greater after both hyperglycemic and hyperinsulinemic clamps as compared to saline infusion (6.6+/-2.6 vs. 1.6+/-0.6 IU/ml, p<0.001; 26+/-4 vs. 1.3+/-0.7 IU/ml, p<0.0001, respectively). Plasma t-PA activity was significantly reduced both after the hyperglycemic (0.36+/-0.15 vs. 2.17+/-0.18 IU/ml in controls, p<0.001) and the hyperinsulinemic (0.3+/-0.1 vs. 2.3+/-0.3 IU/ml in control, p<0.001) clamps. These data show that in vivo both acute hyperglycemia and acute hyperinsulinemia can decrease plasma fibrinolytic potential and that this is due to increased plasma PAI-1 and decreased free t-PA activities.

Impact of Glucose on Outcomes in Patients Treated With Mechanical Thrombectomy

“…18 Postulated mechanisms for this association include that hyperglycemia may be related to atherosclerotic disease or to an antifibrinolytic effect. 19 In contrast, our results demonstrated that hyperglycemia was not related to the reperfusion rate after MT. This result is in line with a recent study reporting the lack of an association between vessel recanalization and diabetes mellitus or glucose levels in patients receiving diverse AF indicates atrial fibrillation; CI, confidence interval; ICH, intracerebral hemorrhage; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; PH, parenchymal hematoma type 2; SICH, symptomatic intracranial haemorrhage; and TIMI, Thrombolysis In Myocardial Ischemia scale.…”

Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis

“…PAI-1 levels are elevated in patients with diabetes mellitus and coronary artery disease [2,21] and are associated with an enhanced risk of coronary events [10,12]. Besides its effects on TF and TFPI, guggulsterone downregulated PAI-1 expression both in quiescent and TNF-a stimulated cells; hence, guggulsterone may be particularly beneficial in patients with diabetes mellitus.…”

High glucose alone, as well as in combination with proinflammatory cytokines, stimulates nuclear factor kappa-B-mediated transcription in hepatocytes in vitro

“…Moreover, further activation of NF-B-dependent transcription was observed with proinflammatory cytokines (IL-1 , TNF-), raising the possibility that NF-B may play a pivotal role in the integration of multiple risk factors seen in the metabolic syndrome. Recent clinical data clearly show that the constellation of risk factors such as hyperglycemia, hyperinsulinemia, and high plasma cytokine levels produces an increase in plasma PAI-1 and fibrinogen, causing enhanced coagulability and impaired fibrinolysis, with 10 resultant increase in the risk of cardiovascular events (Schneider, Nordt, & Sobel, 1993;Pandolfi et al, 2001). Our data also show the increased promoter activity of fibrinogen and PAI-1 genes by glucose, in accordance with the increased plasma level of these proteins and hypercoagulability in patients with uncontrolled diabetes (Bruno et al, 1996;Festa et al, 1999).…”