title: Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus.
abstract: BACKGROUND
  Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus.
  
  
  OBJECTIVE
  To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients.
  
  
  METHODS
  Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE).
  
  
  RESULTS
  Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001).
  
  
  CONCLUSIONS
  Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.
authors.affiliation: Centre of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Santilli
authors.forename: G
authors.initials: G
authors.lastname: Formoso
authors.forename: P
authors.initials: P
authors.lastname: Sbraccia
authors.forename: M
authors.initials: M
authors.lastname: Averna
authors.forename: R
authors.initials: R
authors.lastname: Miccoli
authors.forename: P
authors.initials: P
authors.lastname: Di Fulvio
authors.forename: A
authors.initials: A
authors.lastname: Ganci
authors.forename: N
authors.initials: N
authors.lastname: Pulizzi
authors.forename: S
authors.initials: S
authors.lastname: Lattanzio
authors.forename: G
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: A
authors.initials: A
authors.lastname: Consoli
authors.forename: R
authors.initials: R
authors.lastname: Lauro
authors.forename: C
authors.initials: C
authors.lastname: Patrono
authors.forename: G
authors.initials: G
authors.lastname: Davì
mesh_terms: D020909:Acarbose / Q000627:therapeutic use*; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy* / Q000652:urine; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007558:Italy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D019518:Postprandial Period; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020909:Acarbose; D001120:Arginine; D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D023201:CD40 Ligand; D015237:Dinoprost; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D019007:P-Selectin; D013929:Thromboxane B2; C517652:hemoglobin A1c protein, human; C075750:8-epi-prostaglandin F2alpha; C018524:N,N-dimethylarginine; C049235:11-dehydro-thromboxane B2