Low fasting glucose is associated with enhanced thrombin generation and unfavorable fibrin clot properties in type 2 diabetic patients with high cardiovascular risk

Grzegorz Gajos, Malgorzata Konieczynska, Jaroslaw Zalewski, Anetta Undas

To investigate the effect of low blood glucose on thrombin generation and fibrin clot properties in type 2 diabetes (T2DM). In 165 patients with T2DM and high cardiovascular risk, we measured ex vivo plasma fibrin clot permeation [Ks], turbidity and efficiency of fibrinolysis including clot lysis time [t50%], together with thrombin generation and platelet activation markers in relation to fasting blood glucose. As compared to patients in medium (4.5-6.0 mmol/l, n = 52) and higher (>6.0 mmol/l, n = 75) glucose group, subjects with low glycemia (<4.5 mmol/l, n = 38) had lower Ks by 11% (p < 0.001) and 8% (p = 0.01), respectively, prolonged t50% by 10% (p < 0.001) and 7% (p = 0.016), respectively, and higher peak thrombin generation by 21% and 16%, respectively (p < 0.001 for both). There were no significant differences in Ks and t50% between patients in medium and higher glucose group. In the whole group, a J-shape relationship was observed between glycemia and the following factors: peak thrombin generation, Ks and t50%. Only in patients with HbA1c < 6.0% (42 mmol/mol) (n = 26) fasting glucose positively correlated with Ks (r = 0.53, P = 0.006) and inversely with t50% (r = -0.46, P = 0.02). By multiple regression analysis, after adjustment for age, fibrinogen, HbA1c, insulin treatment and T2DM duration, fasting glycemia was the independent predictor of Ks (F = 6.6, df = 2, P = 0.002), t50% (F = 8.0, df = 2, P < 0.001) and peak thrombin generation (F = 13.5, df = 2, P < 0.0001). In T2DM patients fasting glycemia <4.5 mmol/l is associated with enhanced thrombin formation and formation of denser fibrin clots displaying lower lysability.