The effect of mild agonist stimulation on the platelet reactivity in patients with type 2 diabetes mellitus

BMC Endocr Disord. 2019 Jun 14;19(1):62. doi: 10.1186/s12902-019-0391-2.

Abstract

Background: Patients 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.

Methods: Blood 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.

Results: The 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).

Conclusions: The 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.

Keywords: Adenosine diphosphate (ADP); Desensitization; Platelets; Type 2 diabetes.

MeSH terms

  • Adenosine Diphosphate / pharmacology*
  • Biomarkers / analysis
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • P-Selectin / metabolism
  • Platelet Activation / drug effects*
  • Prognosis

Substances

  • Biomarkers
  • P-Selectin
  • SELP protein, human
  • Adenosine Diphosphate