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

OBJECTIVE: To investigate the effect of low blood glucose on thrombin generation and fibrin clot properties in type 2 diabetes (T2DM). METHODS: In 165 patients with T2DM and high cardiovascular risk, we measured ex vivo plasma fibrin clot permeation [K(s)], turbidity and efficiency of fibrinolysis including clot lysis time [t(50%)], together with thrombin generation and platelet activation markers in relation to fasting blood glucose. RESULTS: 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 K(s) by 11% (p < 0.001) and 8% (p = 0.01), respectively, prolonged t(50%) 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 K(s) and t(50%) 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, K(s) and t(50%). Only in patients with HbA1c < 6.0% (42 mmol/mol) (n = 26) fasting glucose positively correlated with K(s) (r = 0.53, P = 0.006) and inversely with t(50%) (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 K(s) (F = 6.6, df = 2, P = 0.002), t(50%) (F = 8.0, df = 2, P < 0.001) and peak thrombin generation (F = 13.5, df = 2, P < 0.0001). CONCLUSIONS: In T2DM patients fasting glycemia <4.5 mmol/l is associated with enhanced thrombin formation and formation of denser fibrin clots displaying lower lysability, especially when strict glycemia control was achieved (HbA1c<6.0%).