title: Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus.
abstract: OBJECTIVE
  The aim of our study was to assess whether acute, short-term hyperglycemia affects platelet reactivity in patients with Type II diabetes mellitus (T2DM).
  
  
  BACKGROUND
  Hyperglycemic spikes are thought to precipitate ischemic events in T2DM. Previous studies have shown in vivo platelet activation in diabetes; however, no studies have assessed whether acute in vivo hyperglycemia induces further activation of platelets.
  
  
  METHODS
  In a cross-over, randomized, double-blind study, 12 patients with T2DM underwent 4 h of either acute hyperglycemia (13.9 mmol/l, 250 mg/dl) or euglycemia (5.5 mmol/l, 100 mg/dl). Shear stress-induced platelet activation, P-selectin and lysosomal integral membrane protein (LIMP) expression on platelets in the bleeding-time blood, urinary 11-dehydro-thromboxane B(2) (TxB(2)) excretion, von Willebrand factor:antigen (vWF:Ag), and von Willebrand factor:activity (vWF:activity) were measured before and after hyperglycemia or euglycemia.
  
  
  RESULTS
  Shear stress-induced platelet activation, P-selectin and LIMP expression on platelets in the bleeding-time blood, and urinary 11-dehydro-TxB(2) excretion increased significantly after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping. Plasma vWF:Ag and vWF:activity increased strikingly in parallel fashion after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping.
  
  
  CONCLUSIONS
  Our data demonstrate that acute, short-term hyperglycemia induces an increased activation of platelets exposed to high shear stress conditions in vitro (filtration method) or in vivo (bleeding time). In vivo platelet activation is reflected by an increased urinary excretion of 11-dehydro-TxB(2). The increased levels of vWF in the circulation correlate with the increase in platelet activation markers and may indicate some degree of causation. Acute, short-term hyperglycemia in T2DM may precipitate vascular occlusions by facilitating platelet activation.
authors.affiliation: Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, via E. Dal Pozzo, snc-06126, Perugia, Italy. grespa@unipg.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Guglielmini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: De Angelis
authors.forename: Silvia
authors.initials: S
authors.lastname: Ciferri
authors.forename: Marco
authors.initials: M
authors.lastname: Ciofetta
authors.forename: Emanuela
authors.initials: E
authors.lastname: Falcinelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Lalli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
authors.forename: Geremia B
authors.initials: GB
authors.lastname: Bolli
mesh_terms: D000208:Acute Disease; D000368:Aged; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology* / Q000503:physiopathology*; D015539:Platelet Activation / Q000502:physiology*; D012307:Risk Factors; D033081:Shear Strength; D013312:Stress, Physiological / Q000503:physiopathology*; D013997:Time Factors