Objectives: This study sought to assess the influence of type 2 diabetes mellitus(T2DM) and the impact of hypoglycemic treatment(insulin vs. noninsulin) on platelet function profiles in patients treated with dual oral antiplatelet therapy. Background: Insulin inhibits platelet aggregation by suppressing the P2Y12 pathway. However, T2DM patients have a loss of responsiveness to insulin that leads to upregulation of the P2Y12 pathway, increased platelet reactivity, and reduced responsiveness to antiplatelet agents. Patients with insulin-treated diabetes mellitus(ITDM) have a more advanced disease status and higher atherothrombotic risk compared with non-ITDM (NITDM).However, the impact of insulin therapy on platelet dysfunction in patients treated with P2Y12 antagonists is unknown. Methods: A total of 201 T2DM and 65 nondiabetic patients with coronary artery disease in a steady phase of aspirin and clopidogrel treatment were studied. Platelet aggregation was assessed using agonists specific(6 and 20 μM adenosine diphosphate[ADP]) and nonspecific(6 μg/ml collagen and 20 μM epinephrine) for the P2Y12 pathway. High shear-induced platelet reactivity was assessed by means of the PFA-100 system(Dade-Behring International, Miami, Florida). Results: The T2DM patients had platelet aggregation and shear-induced platelet function significantly increased compared with nondiabetic patients using all assays. Platelet aggregation was increased in ITDM(n=68) compared with NITDM(n=133) patients after P2Y12-specific stimuli. Insulin treatment was the strongest predictor of ADP-induced aggregation. Platelet function profiles were similar between ITDM and NITDM using assays nonspecific to the P2Y12 pathway. Platelet dysfunction was independent of glycemic control and inflammatory status. Conclusions: The P2Y12-dependent and -independent pathways of platelet reactivity are altered in T2DM compared with nondiabetic patients, and ITDM have greater ADP-induced platelet aggregation compared with NITDM.
展开▼
