Royal College of Surgeons in Ireland
Type 2 Diabetes Coagulopathy Proteins May Conflict With Biomarkers Reflective of COVID-19 Severity.pdf (703.34 kB)

Type 2 diabetes coagulopathy proteins may conflict with biomarkers reflective of COVID-19 severity

Download (703.34 kB)
Version 2 2022-07-15, 10:07
Version 1 2022-02-10, 17:05
journal contribution
posted on 2022-02-10, 17:05 authored by Abu Saleh Md Moin, Ahmed Al-Qaissi, Thozhukat Sathyapalan, Stephen L Atkin, Alexandra E Butler

Objective: 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.

Methods: 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.

Results: Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2D versus 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 < 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 versus baseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p < 0.014), platelet factor-4 (p < 0.01), Platelet basic protein (p < 0.008), and Vitamin K-dependent protein-C (p < 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p < 0.0002)].

Conclusion: Seven of 34 proteins suggested to be biomarkers of COVID-19 severity within the platelet degranulation and complement and coagulation cascades differed in T2D versus 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.

Clinical trial registration:, identifier NCT03102801



The original article is available at

Published Citation

Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Type 2 diabetes coagulopathy proteins may conflict with biomarkers reflective of COVID-19 severity. Front Endocrinol (Lausanne). 2021;12:658304

Publication Date

25 June 2021

PubMed ID



  • RCSI Bahrain


Frontiers Research Foundation


  • Published Version (Version of Record)