Platelet and monocyte activation by hyperglycemia and hyperinsulinemia in healthy subjects

Platelets. 2006 Dec;17(8):577-85. doi: 10.1080/09537100600760814.


Type 2 diabetes mellitus (T2DM) patients have hyperglycemia and hyperinsulinemia and increased risk of atherosclerosis and acute vascular complications. We have reported elevated circulating tissue factor procoagulant activity (TF-PCA) during hyperglycemia (HG) and hyperinsulinemia (HI) in normal subjects. To evaluate the effect of hyperglycemia and hyperinsulinemia on blood cell activation, we assessed platelet CD40L and P-selectin, monocyte tissue factor (TF), and the formation of monocyte-platelet and neutrophil-platelet aggregates. These were assessed in the resting state and following activation with ADP and thrombin (SFLLRN). Healthy individuals were subjected to 24 h of hyperglycemia and hyperinsulinemia, selective hyperglycemia, selective hyperinsulinemia, or normal glucose and insulin. Platelet CD40L expression increased with high glucose/high insulin, selective hyperglycemia and selective hyperinsulinemia. Monocyte-platelet aggregates increased with high glucose/high insulin. Monocyte TF expression increased with high glucose/high insulin and with selective hyperinsulinemia. Upon stimulation with ADP and SFLLRN, monocyte-platelet and neutrophil-platelet aggregates, platelet CD40L and P-selectin, and monocyte TF increased compared to the resting state but was not different between 0 and 24 h, indicating that the responsiveness to those agonists was not altered.

Conclusions: Hyperglycemia-hyperinsulinemia in healthy individuals induced platelet activation and monocyte TF expression promoting a procoagulant and proinflammatory state that may contribute to acute vascular events and atherogenesis. Platelet responsiveness to activation with ADP or SFLLRN appears not to be altered by hyperglycemia-hyperinsulinemia.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adult
  • Atherosclerosis / blood
  • Atherosclerosis / etiology
  • Blood Platelets / metabolism*
  • Blood Proteins / analysis
  • Diabetes Complications / blood
  • Diabetes Mellitus, Type 2 / blood
  • Female
  • Humans
  • Hyperglycemia / blood*
  • Hyperglycemia / etiology
  • Hyperinsulinism / blood*
  • Inflammation / blood
  • Inflammation / etiology
  • Macrophage Activation* / drug effects
  • Male
  • Monocytes / metabolism*
  • Peptide Fragments / pharmacology
  • Platelet Aggregation* / drug effects


  • Blood Proteins
  • Peptide Fragments
  • thrombin receptor peptide (42-47)
  • Adenosine Diphosphate