Hyperglycemia can enhance thrombogenicity The more that HbA1c levels are reduced, the greater the reduction in thrombus formation, according to a double-blind study involving an insulin sensitizer in patients with type 2 diabetes.
All 40 patients studied, who had elevated HbA10 values (>7.5%) despite dietary modification and treatment with insulin or sulfonylurea, or both, were randomized to receive a placebo or troglitazone (800 mglday) for 3 months, during which their previous regimen was continued.
Studies at baseline and at 3 months included thrombogenicity assessment using a recently developed ex vivo perfusion chamber that allows histologic measurement of thrombus formation over porcine sortie tunica media; the effect of clinically significant glycemic control (defined as HbA1ç reduction of 0.5% or more) on thrombogenicity was measured as the change in the area of the thrombus at baseline and at 3 months.
Patients in both the trogiftazone (74%) and placebo (46%) groups frequently experienced significant glycemic control, which in turn was the only independent variable associated with significant thrombus reduction. Patients who had no glycemic improvement showed no change in thrornbogenicity. However, the possibility that troglitazone had an antithrombotlc effect In addition to glucose lowering cannot be excluded by this study design.
The investigators noted that their findings contrast with those of previous groups, who had failed to find a link between Improved glycemic control and reduced hypercoagulability in patients with diabetes. They suggested that techniques previously used (such as in vitro platelet aggregation and measurement of plasma proteins) cannot accurately assess hypercoagulability. Rather, they argued that the perfusion chamber technique makes such measurements possible by mimicking the high-shear conditions present in a mildly stenotic coronary artery
The findings support the hypothesis that hyperglycemia can enhance thrombogenicity (perhaps by accelerating the formation of advanced glycosalated end products), and conversely that giycemlc control can inhiblt thrombogenicity. More broadly, they lend credence to the view that the hypercoaguuuulable state should be added to the list of risk factors for thrombotic complications of atherosclerosis in type 2 diabetes.
Ounde Jl et al. Blood thrombogenicity in type 2 diabetes patients is associated with glycemic control. Jam Coll Cardiol. 2001:38:1307-1312.