Abstract
BackgroundPatients with type 2 diabetes mellitus (T2DM) have accelerated atherosclerosis as a pro thrombotic state that is associated with the platelet activation priming. Platelets, which undergo the continuous mild stimulation, may lose their sensitivity to react to a strong stimulation. The present study aimed to investigate activation responses of platelets to mild and subsequent strong stimulations in patients with T2DM and healthy individuals.MethodsBlood samples, which were taken from 40 patients with T2DM and 35 healthy individuals, were collected into the citrate containing tubes. The samples were subjected to the soft centrifugation to prepare the platelet rich plasma (PRP). Platelets in PRP samples were treated at a low (1 μM) concentration and then at a high (10 μM) concentration of ADP. Before and after stimulation with different doses of ADP, levels of CD62P expression and formation of platelet micro particles (PMPs) were measured using a flow cytometry method.ResultsThe platelets from patients with T2DM had higher levels of CD62P expression before any stimulation (P = 0.003) than control samples. Platelets, which underwent the mild stimulation, indicated lower responses to CD62P expression, but higher PMPs formation after stimulation with high dose of ADP. Patients with T2DM had higher platelet micro particles in all states with the ADP stimulation. (P = 0.004, SD: ±74.52).ConclusionsThe flow cytometry data indicated that platelets were pre-active and associated with metabolic conditions in patients with type 2 diabetes mellitus. The induction of desensitization state helped platelets to reduce the platelet activation and sensitivity to ADP in a diabetic environment. Furthermore, the production of platelets micro-particles was high in the patients; and desensitized platelets were more susceptible to shedding of micro-particles.
Highlights
Patients with type 2 diabetes mellitus (T2DM) have accelerated atherosclerosis as a pro thrombotic state that is associated with the platelet activation priming
The flow cytometry analysis indicated that platelets of patients with T2DM had a higher expression of CD62P at the resting stage, and they expressed a higher level of CD62P even in the absence of exogenous Adenosine diphosphate (ADP)
In the second to forth tube of platelet rich plasma (PRP), this increased expression of CD62P was greater in patients with T2DM in comparison with healthy participants; and the difference was due to the pre-activity of platelets at the baseline stage (Fig. 3)
Summary
Patients with type 2 diabetes mellitus (T2DM) have accelerated atherosclerosis as a pro thrombotic state that is associated with the platelet activation priming. Platelet micro-particles (PMPs) are small cellular fragments within the range of 0.1 to 1 μm that are separated from the membrane of activated platelets, stressed platelets, and apoptotic platelets through shedding. They have phospholipid plasma membrane and inherit a variety of functional receptors from platelets [10, 11]. Coagulation activities of PMPs are 50 to 100 times more than active platelets; they are considered as potential targets for the reduction of atherosclerosis development in diabetes [14]
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