{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T16:41:50Z","timestamp":1788021710306,"version":"build-2784847793"},"reference-count":25,"publisher":"American Diabetes Association","issue":"6","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":4181,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,6,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Acute, short-term hyperglycemia enhances high shear stress\u2013induced 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\u2013donating agent (NCX 4016), their combination, or placebo on platelet activation induced by acute hyperglycemia in type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Acute hyperglycemia enhanced shear stress\u2013induced platelet activation in placebo-treated patients (basal closure time 63 \u00b1 7.1 s, after hyperglycemia 49.5 \u00b1 1.4 s, \u221213.5 \u00b1 6.3 s, P &amp;lt; 0.048). Pretreatment with aspirin, despite full inhibition of platelet COX-1, did not prevent it (\u221212.7 \u00b1 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 \u00b1 8.3 s; NCX 4016 plus aspirin: +12.0 \u00b1 10.7 s, P &amp;lt; 0.05 vs. placebo for both). Other parameters of shear stress\u2013dependent platelet activation were also more inhibited by NCX 4016 than by aspirin, despite lesser inhibition of COX-1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc09-2013","type":"journal-article","created":{"date-parts":[[2010,3,19]],"date-time":"2010-03-19T00:46:55Z","timestamp":1268959615000},"page":"1262-1268","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":47,"title":["Hyperglycemia-Induced Platelet Activation in Type 2 Diabetes Is Resistant to Aspirin but Not to a Nitric Oxide\u2013Donating Agent"],"prefix":"10.2337","volume":"33","author":[{"given":"Paolo","family":"Gresele","sequence":"first","affiliation":[{"name":"Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Marzotti","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine, Endocrinology and Metabolism, Department of Internal Medicine, University of Perugia, Perugia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Guglielmini","sequence":"additional","affiliation":[{"name":"Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Momi","sequence":"additional","affiliation":[{"name":"Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Giannini","sequence":"additional","affiliation":[{"name":"Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Minuz","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Surgical Sciences, University of Verona, Verona, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Lucidi","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine, Endocrinology and Metabolism, Department of Internal Medicine, University of Perugia, Perugia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geremia B.","family":"Bolli","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine, Endocrinology and Metabolism, Department of Internal Medicine, University of Perugia, Perugia, 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