AUTHOR=Moin Abu Saleh Md , Al-Qaissi Ahmed , Sathyapalan Thozhukat , Atkin Stephen L. , Butler Alexandra E. 

TITLE=Type 2 Diabetes Coagulopathy Proteins May Conflict With Biomarkers Reflective of COVID-19 Severity

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.658304

DOI=10.3389/fendo.2021.658304

ISSN=1664-2392

ABSTRACT=<sec><title>Objective</title><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.</p></sec><sec><title>Methods</title><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 ± 0.07 mmol/L (81 ± 1.2 mg/dl)] for 1-h, following which blood glucose was decreased to ≤2.0 mmol/L (36 mg/dl). Proteomic analysis for the complement and coagulation cascades were measured using Slow Off-rate Modified Aptamer (SOMA)-scan.</p></sec><sec><title>Results</title><p>Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2D <italic>versus</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 &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 <italic>versus</italic> baseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p &lt; 0.014), platelet factor-4 (p &lt; 0.01), Platelet basic protein (p &lt; 0.008), and Vitamin K-dependent protein-C (p &lt; 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p &lt; 0.0002)].</p></sec><sec><title>Conclusion</title><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 <italic>versus</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.</p></sec><sec><title>Clinical Trial Registration</title><p><uri xlink:href="https://clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/</uri>, identifier NCT03102801.</p></sec>