6533b824fe1ef96bd12809b6
RESEARCH PRODUCT
POSTPRANDIAL HYPERGLYCEMIA IS A DETERMINANT OF PLATELET ACTIVATION IN EARLY 2 DIABETES MELLITUS
Roberto MiccoliCarlo PatronoGiovanni CiabattoniMaurizio AvernaR LauroAntonino ConsoliStefano LattanzioN PulizziP. Di FulvioP SbracciaA. GanciF. SantilliGloria FormosoGiovanni Davìsubject
Blood GlucoseMaleTime FactorsSettore MED/09 - Medicina InternaDinoprostpostprandial hyperglycemia; platelet activationMedicineEnzyme InhibitorsSettore MED/49 - Scienze Tecniche Dietetiche Applicatepostprandial hyperglycemiaAcarboseplateletHemoglobin AHematologyMiddle AgedPostprandial PeriodP-SelectinPostprandialTreatment OutcomeC-Reactive ProteinItalyFemaleBiological MarkersAcarboseType 2medicine.drugacarbose platelet activation postprandial hyperglycemia type 2 diabetes mellitusmedicine.medical_specialtySettore BIO/14 - FARMACOLOGIAUrinary systemCD40 LigandGlycosylatedArginineExcretionBlood Glucose; Time Factors; Lipid Peroxidation; Middle Aged; Hemoglobin A Glycosylated; Postprandial Period; Diabetes Mellitus Type 2; Enzyme Inhibitors; Hypoglycemic Agents; P-Selectin; Platelet Activation; Aged; CD40 Ligand; Treatment Outcome; Male; Female; Thromboxane B2; Dinoprost; Italy; Arginine; Acarbose; Double-Blind Method; Humans; Biological Markers; Hyperglycemia; alpha-Glucosidases; C-Reactive ProteinDouble-Blind MethodInternal medicineDiabetes mellitusDiabetes MellitusHypoglycemic AgentsHumansGlycoside Hydrolase InhibitorsPlatelet activationGlycemicAgedGlycated Hemoglobinbusiness.industryType 2 Diabetes Mellitusalpha-Glucosidasesmedicine.diseasePlatelet ActivationThromboxane B2EndocrinologyDiabetes Mellitus Type 2HyperglycemiaLipid PeroxidationbusinessBiomarkersdescription
BACKGROUND: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. OBJECTIVES: 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-04-01 |