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

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

Abstract

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.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT03102801, identifier NCT03102801.

Keywords: COVID-19; SARS-CoV-2; obesity; platelet; type 2 diabetes.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Moin, Al-Qaissi, Sathyapalan, Atkin and Butler.

Figures

Figure 1
Figure 1
Circulatory levels of platelet related proteins in obese type 2 diabetes (OT2D) and control subjects. Plasma protein levels of platelet factor 4 (PF4) (A), platelet glycoprotein VI (PGVI) (B), P-selectin (C), plasminogen activator inhibitor I (PAI-1) (D), plasmin (E), plasmin and heparin cofactor II (F). Age correlated with levels of PF4 (r = 0.58) (G), P-selectin (r = 0.51) (H) and Heparin cofactor II (r = 0.56) (I) in the T2D cohort only. RFU: relative fluorescent units; *p < 0.05; **p < 0.01.
Figure 2
Figure 2
Circulatory levels of platelet related proteins in obese type 2 diabetes (OT2D) and control subjects stratified according to gender. Plasma protein levels of platelet factor 4 (PF4) (A), platelet glycopsrotein VI (PGVI) (B), P-selectin (C), plasminogen activator inhibitor I (PAI-1) (D), plasmin (E), plasmin and heparin cofactor II (F). RFU: relative fluorescent units; *p < 0.05; **p < 0.01; ****p < 0.0001.

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