Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease

Aims Platelets participate in the pathogenesis of arterial thrombosis and it has been demonstrated that enhanced platelet activation occurs in patients with diabetes mellitus (DM). Dyslipidaemia is a common feature of diabetes. We investigated the association between certain lipid fractions and plasma platelet-derived microparticle (PMP) levels in patients with type-2 DM. Methods and results We measured fasting serum levels of remnant-like lipoprotein particles-cholesterol (RLP-cholesterol) and assessed in vivo platelet activation by quantifying the number of PMP in the plasma detected as CD42b-positive microparticles by flow cytometry in Japanese type-2 DM patients without obstructive coronary artery disease who were more slender when compared with Western diabetic patients. The levels of total cholesterol, triglycerides, RLP-cholesterol, and plasma glucose were significantly higher in patients with type-2 DM (n=105) than in non-diabetic patients (n=92). The plasma levels of PMP were elevated significantly in type-2 DM patients when compared with non-diabetic control subjects [7.41(5.39-10.50)x10(6) vs. 3.44(2.43-4.41)x10(6), P < 0.001]. We found that RLP-cholesterol levels were the best predictor of PMP in multivariable linear regression analyses (beta=0.375, P < 0.001). Lipid-lowering medication with bezafibrate successfully reduced levels of both RLP-cholesterol and PMP in patients with type-2 DM (P < 0.05). Conclusions RLP-cholesterol and platelet microparticles are both elevated in type-2 DM patients when compared with controls. RLP-cholesterol is the primary and only predictor of platelet microparticles in the multivariable analysis, which include several standard atherosclerosis risk factors. This suggested that reducing elevated RLP-cholesterol with lipid-lowering therapy may be an effective strategy to prevent thrombogenic vascular complications in type-2 DM.