Hyperglycemia-Induced Platelet Activation in Type 2 Diabetes Is Resistant to Aspirin but Not to a Nitric Oxide–Donating Agent
Open Access
- 18 March 2010
- journal article
- research article
- Published by American Diabetes Association in Diabetes Care
- Vol. 33 (6), 1262-1268
- https://doi.org/10.2337/dc09-2013
Abstract
OBJECTIVE: Acute, short-term hyperglycemia enhances high shear stress–induced platelet activation in type 2 diabetes. Several observations suggest that platelets in type 2 diabetes are resistant to inhibition by aspirin. Our aim was to assess comparatively the effect of aspirin, a nitric oxide–donating agent (NCX 4016), their combination, or placebo on platelet activation induced by acute hyperglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a double-blind, placebo-controlled, randomized trial, 40 type 2 diabetic patients were allocated to 100 mg aspirin once daily, 800 mg NCX 4016 b.i.d., both of them, or placebo for 15 days. On day 15, 1 h after the morning dose, a 4-h hyperglycemic clamp (plasma glucose 13.9 mmol/l) was performed, and blood samples were collected before and immediately after it for platelet activation and cyclooxygenase-1 (COX-1) inhibition studies. RESULTS: Acute hyperglycemia enhanced shear stress–induced platelet activation in placebo-treated patients (basal closure time 63 ± 7.1 s, after hyperglycemia 49.5 ± 1.4 s, −13.5 ± 6.3 s, P < 0.048). Pretreatment with aspirin, despite full inhibition of platelet COX-1, did not prevent it (−12.7 ± 6.9 s, NS vs. placebo). On the contrary, pretreatment with the NO donor NCX 4016, alone or in combination with aspirin, suppressed platelet activation induced by acute hyperglycemia (NCX 4016 +10.5 ± 8.3 s; NCX 4016 plus aspirin: +12.0 ± 10.7 s, P < 0.05 vs. placebo for both). Other parameters of shear stress–dependent platelet activation were also more inhibited by NCX 4016 than by aspirin, despite lesser inhibition of COX-1. CONCLUSIONS: Acute hyperglycemia-induced enhancement of platelet activation is resistant to aspirin; a NO-donating agent suppresses it. Therapeutic approaches aiming at a wider platelet inhibitory action than that exerted by aspirin may prove useful in patients with type 2 diabetes.This publication has 27 references indexed in Scilit:
- Von Willebrand Factor, Type 2 Diabetes Mellitus, and Risk of Cardiovascular DiseaseCirculation, 2008
- Searching for New NO-Donor Aspirin-like Molecules: A New Class of Nitrooxy-acyl Derivatives of Salicylic AcidJournal of Medicinal Chemistry, 2008
- Platelets release active matrix metalloproteinase‐2 in vivo in humans at a site of vascular injury: lack of inhibition by aspirinBritish Journal of Haematology, 2007
- Pharmacologic Profile and Therapeutic Potential of NCX 4016, a Nitric Oxide‐releasing Aspirin, for Cardiovascular DisordersCardiovascular Drug Reviews, 2006
- Direct and Irreversible Inhibition of Cyclooxygenase-1 by Nitroaspirin (NCX 4016)The Journal of pharmacology and experimental therapeutics, 2005
- Platelet activation in type 2 diabetes mellitusJournal of Thrombosis and Haemostasis, 2004
- Chemiluminescence and LC–MS/MS analyses for the study of nitric oxide release and distribution following oral administration of nitroaspirin (NCX 4016) in healthy volunteersJournal of Pharmaceutical and Biomedical Analysis, 2004
- Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patientsBMJ, 2002
- Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric OxideCirculation Research, 2002
- The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years.Diabetes Care, 1999