title: Aspirin sensitivity of platelet aggregation in diabetes mellitus.
abstract: Although aspirin is cardioprotective in high-risk populations, many with diabetes mellitus (DM) are unresponsive to these benefits. We questioned whether cardiovascular unresponsiveness might be demonstrated by lack of aspirin sensitivity to in vitro platelet functions especially in subjects with poorly controlled diabetes. Six women and 4 men (48+/-8 years [mean+/-S.D.]), selected for poor control (glycohemoglobin 11.9+/-2.2%) and 10 sex-age (+/-5 years) matched controls received 81 mg aspirin daily. There was a 2-week washout from aspirin and related drugs. After the aspirin dose on day-7, blood for platelet aggregation assays, and 24-h urine for 2,3 dinor thromboxane B2 (TxB2) and 2,3 dinor 6-keto (PGF1alpha) were obtained. Aspirin sensitivity was defined as inhibition (i.e., lower than expected) platelet aggregation after exposure to an agonist. Those with diabetes and controls were sensitive to aspirin inhibition of platelet aggregation induced by 1.6 mM arachidonic acid (9.5+/-3.9% versus 9.1+/-3.1%, normal range 40-100%) and by 0.83 microg/mL collagen (17.4+/-13.9% versus 13.2+/-9.3%, normal range 60-93%), respectively. Aspirin sensitivity to 2 microM ADP was present in five with diabetes and five controls. Urinary prostaglandin metabolites were suppressed below reference ranges, without differences between those with DM or controls for TxB2 (350+/-149 pg/mg versus 348+/-93 pg/mg creatinine) and PGF1alpha (255+/-104 pg/mg versus 222+/-88 pg/mg creatinine). In conclusion, in poorly controlled diabetes, there was no differential lack of aspirin sensitivity to platelet aggregation, or lack of aspirin suppression of urinary TxB2 or PGF1alpha, compared with controls on aspirin. Despite suppression of urinary prostaglandin metabolites, aspirin resistance was most apparent to ADP-mediated platelet aggregation. It is not known what level of inhibition of in vitro tests is necessary for the cardioprotective benefits of aspirin in diabetes mellitus. Thus, the lack of aspirin protection in diabetes may be due to undefined aspects of platelet function.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, MO 63104, USA. albertsg@slu.edu
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Albert
authors.forename: Bibi I
authors.initials: BI
authors.lastname: Hasnain
authors.forename: Detlef G
authors.initials: DG
authors.lastname: Ritter
authors.forename: J Heinrich
authors.initials: JH
authors.lastname: Joist
authors.forename: Arshag D
authors.initials: AD
authors.lastname: Mooradian
mesh_terms: D001241:Aspirin / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin