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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%).

cardiovascular diabetology

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