{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:39:36Z","timestamp":1773297576157,"version":"3.50.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"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>Objective<\/jats:title><jats:p>Detailed proteomic analysis in a cohort of patients with differing severity of COVID-19 disease identified biomarkers within the complement and coagulation cascades as biomarkers for disease severity has been reported; however, it is unclear if these proteins differ sufficiently from other conditions to be considered as biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective, parallel study in T2D (n = 23) and controls (n = 23). A hyperinsulinemic clamp was performed and normoglycemia induced in T2D [4.5 \u00b1 0.07 mmol\/L (81 \u00b1 1.2 mg\/dl)] for 1-h, following which blood glucose was decreased to \u22642.0 mmol\/L (36 mg\/dl). Proteomic analysis for the complement and coagulation cascades were measured using Slow Off-rate Modified Aptamer (SOMA)-scan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2D<jats:italic>versus<\/jats:italic>controls for platelet degranulation [Neutrophil-activating peptide-2 (p = 0.014), Thrombospondin-1 (p = 0.012), Platelet factor-4 (p = 0.007), and Kininogen-1 (p = 0.05)], whilst 3 of 16 proteins differed for complement and coagulation cascades [Coagulation factor IX (p &amp;lt; 0.05), Kininogen-1 (p = 0.05), and Heparin cofactor-2 (p = 0.007)]; STRING analysis demonstrated the close relationship of these proteins to one another. Induced euglycemia in T2D showed no protein changes<jats:italic>versus<\/jats:italic>baseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p &amp;lt; 0.014), platelet factor-4 (p &amp;lt; 0.01), Platelet basic protein (p &amp;lt; 0.008), and Vitamin K-dependent protein-C (p &amp;lt; 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p &amp;lt; 0.0002)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Seven of 34 proteins suggested to be biomarkers of COVID-19 severity within the platelet degranulation and complement and coagulation cascades differed in T2D<jats:italic>versus<\/jats:italic>controls, with further changes occurring at hypoglycemia, suggesting that validation of these biomarkers is critical. It is unclear if these protein changes in T2D may predict worse COVID-19 disease for these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/clinicaltrials.gov\/<\/jats:uri>, identifier NCT03102801.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.658304","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T07:28:34Z","timestamp":1624606114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Type 2 Diabetes Coagulopathy Proteins May Conflict With Biomarkers Reflective of COVID-19 Severity"],"prefix":"10.3389","volume":"12","author":[{"given":"Abu Saleh 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