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 [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.


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 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).


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%).
Department of Coronary Disease and Heart Failure, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka str, 31-202, Krakow, Poland. grzegorz.gajos@uj.edu.pl.
Grzegorz
G
Gajos
John Paul II Hospital, Krakow, Poland. m.konieczynska@szpitaljp2.krakow.pl.
Malgorzata
M
Konieczynska
Department of Coronary Disease and Heart Failure, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka str, 31-202, Krakow, Poland. jzalews@szpitaljp2.krakow.pl.
Jaroslaw
J
Zalewski
Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. mmundas@cyf-kr.edu.pl.
Anetta
A
Undas
D000368:Aged; D001777:Blood Coagulation / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D005215:Fasting / Q000097:blood*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism*
D001786:Blood Glucose; D005337:Fibrin; D013917:Thrombin