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Platelet Protein-Related Abnormalities in Response to Acute Hypoglycemia in Type 2 Diabetes

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


Abu Saleh Md Moin

Ahmed Al-Qaissi

Thozhukat Sathyapalan

Stephen L. Atkin

Alexandra E. Butler


Introduction: 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.

Methods: 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 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins.

Results: Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p < 0.05); platelet glycoprotein VI (PGVI p < 0.05); P-selectin (p < 0.01) and plasminogen activator inhibitor I (PAI-1, p < 0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p < 0.05) and heparin cofactor II (HCFII, p < 0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels.

Conclusion: 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.


Moin, A. S. M., Al-Qaissi, A., Sathyapalan, T., Atkin, S. L., & Butler, A. E. (2021). Platelet Protein-Related Abnormalities in Response to Acute Hypoglycemia in Type 2 Diabetes. Frontiers in endocrinology, 12,

Journal Article Type Article
Acceptance Date Mar 16, 2021
Online Publication Date Mar 30, 2021
Publication Date Mar 30, 2021
Deposit Date May 15, 2021
Publicly Available Date May 18, 2021
Journal Frontiers in Endocrinology
Print ISSN 1664-2392
Electronic ISSN 1664-2392
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 12
Article Number 651009
Keywords Type 2 diabetes; Obesity; Platelet; COVID-19, SARS-CoV-2
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Copyright Statement
Copyright © 2021 Moin, Al-Qaissi, Sathyapalan, Atkin and Butler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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