Interplay between elevated cellular fibronectin and plasma fibrin clot properties in type 2 diabetes

Type 2 diabetes is associated with faster formation of poorly lysable, denser fibrin clots and elevated cellular fibronectin (cFn), a marker of vascular injury. We investigated whether cFn affects clot properties in type 2 diabetes. In 200 consecutive patients with type 2 diabetes and 100 control subjects matched for age and sex, we determined plasma cFn along with clot formation and degradation using turbidimetric and permeability assays. Diabetic patients had elevated cFn (median, 3.99 [interquartile range, 2.87-4.81] µg/ml]), increased clot density (MaxAbsC) and prolonged lysis time (LysT) compared with those without type 2 diabetes (all p<0.01). Diabetic patients with documented cardiovascular disease (CVD, n=127, 63.5 %) had increased cFn (4.53 [3.68-4.95] µg/ml), decreased clot permeability (Ks) and increased MaxAbsC compared with those without CVD (all p<0.001). Diabetic patients with cFn in the top quartile (>4.81 µg/ml) were two times more likely to have CVD compared with those in the lowest quartile (odds ratio 1.80, 95 % confidence interval 1.41-2.46, p<0.001). No differences in cFn were observed in relation to microvascular complications. After adjustment for potential confounders, cFn accounted for 10.2 % of variance in Ks, 18.2 % of variance in clot density and 10.2 % of variance in AUC in diabetic patients. This study shows that elevated cFn is associated with unfavourably modified clot properties in type 2 diabetes, especially with concomitant CVD, which indicates novel links between vascular injury and prothrombotic alterations in diabetes. Coagulation, cellular fibronectin, type 2 diabetes, cardiovascular disease.