title: In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes.
abstract: Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.
authors.affiliation: Diabetes Care Unit, Catholic University School of Medicine, Rome, Italy Diabetes Research Centre, University of Leicester, Leicester, U.K.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccardi
authors.affiliation: Diabetes Care Unit, Catholic University School of Medicine, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rizzi
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Petrucci
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Ciaffardini
authors.affiliation: Diabetes Care Unit, Catholic University School of Medicine, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tanese
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pagliaccia
authors.affiliation: Centro Cardiologico Monzino, Milan, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Cavalca
authors.affiliation: Institute of Hematology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Ciminello
authors.affiliation: INSERM UMR 1149, Centre de Recherche sur l'Inflammation, Université Paris 7 Diderot, Laboratoire d'Excellence Inflamex, Faculté de Médecine Xavier Bichat, Paris, France Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Aida
authors.initials: A
authors.lastname: Habib
authors.affiliation: Centro Cardiologico Monzino, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Squellerio
authors.affiliation: Diabetes Care Unit, Catholic University School of Medicine, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
authors.affiliation: Centro Cardiologico Monzino, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy b.rocca@tiscali.it.
authors.forename: Bianca
authors.identifier: http://orcid.org/0000-0001-8304-6423
authors.initials: B
authors.lastname: Rocca
authors.affiliation: Diabetes Care Unit, Catholic University School of Medicine, Rome, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Pitocco
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Patrono
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000652:urine; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D003430:Cross-Sectional Studies; D051545:Cyclooxygenase 1 / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D055806:Microvessels / Q000503:physiopathology; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012737:Sex Factors; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000652:urine
chemical_list: D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; C075750:8-epi-prostaglandin F2alpha; D013928:Thromboxane A2; D015237:Dinoprost; D011464:Epoprostenol; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin