{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T10:36:52Z","timestamp":1782383812520,"version":"3.54.5"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Patients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 \u00b1 0.3mmol\/l (135.1 \u00b1 5.4mg\/dl), reduced to 4.5 \u00b1 0.07mmol\/l (81 \u00b1 1.2mg\/dl) with 1-hour clamp; Controls: maintained at 5.1 \u00b1 0.1mmol\/l (91.9 \u00b1 1.8mg\/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p&amp;lt;0.05); platelet glycoprotein VI (PGVI p&amp;lt;0.05); P-selectin (p&amp;lt;0.01) and plasminogen activator inhibitor I (PAI-1, p&amp;lt;0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p&amp;lt;0.05) and heparin cofactor II (HCFII, p&amp;lt;0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>T2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03102801<\/jats:uri>, identifier NCT03102801.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.651009","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T17:37:50Z","timestamp":1617125870000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Platelet Protein-Related Abnormalities in Response to Acute Hypoglycemia in Type 2 Diabetes"],"prefix":"10.3389","volume":"12","author":[{"given":"Abu Saleh 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