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The severity and duration of Hypoglycemia affect platelet-derived protein responses in Caucasians

Moin, Abu Saleh Md; Sathyapalan, Thozhukat; Atkin, Stephen L.; Butler, Alexandra E.


Abu Saleh Md Moin

Stephen L. Atkin

Alexandra E. Butler


Objective: Severe hypoglycemia is associated with increased cardiovascular death risk, and platelet responses to hypoglycemia (hypo) have been described. However, the impact of deep transient hypo (deep-hypo) versus prolonged milder hypo (mild-hypo) on platelet response is unclear. Research Design and methods: Two hypo studies were compared; firstly, mild-hypo in 18-subjects (10 type-2-diabetes (T2D), 8 controls), blood glucose to 2.8mmoL/L (50 mg/dL) for 1-hour; secondly deep-hypo in 46-subjects (23 T2D, 23 controls), blood glucose to < 2.2mmoL/L (< 40 mg/dL) transiently. Platelet-related protein (PRP) responses from baseline to after 1-hour of hypo (mild-hypo) or at deep-hypo were compared, and at 24-hours post-hypo. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine PRP changes for 13 PRPs. Results: In controls, from baseline to hypo, differences were seen for four PRPs, three showing increased %change in deep-hypo (Plasminogen activator inhibitor-1(PAI-1), CD40 ligand (CD40LG) and Protein-S), one showing increased %change in mild-hypo (von Willebrand factor (vWF)); at 24-hours in controls, %change for Protein-S remained increased in deep-hypo, whilst % change for vWF and plasminogen were increased in mild-hypo. In T2D, from baseline to hypo, differences were seen for 4 PRPs, three showing increased %change in deep-hypo (PAI-1, platelet glycoprotein VI and Tissue factor), one showing increased %change in mild-hypo (CD40LG); at 24-hours in T2D, %change for CD40LG remained increased, together with vWF, in deep-hypo. Conclusion: Both mild-hypo and deep-hypo showed marked PRP changes that continued up to 24-hours, showing that both the severity and duration of hypoglycemia are likely important and that any degree of hypoglycemia may be detrimental for increased cardiovascular risk events through PRP changes.


Moin, A. S. M., Sathyapalan, T., Atkin, S. L., & Butler, A. E. (2022). The severity and duration of Hypoglycemia affect platelet-derived protein responses in Caucasians. Cardiovascular Diabetology, 21(1), Article 202.

Journal Article Type Article
Acceptance Date Sep 23, 2022
Online Publication Date Oct 6, 2022
Publication Date Dec 1, 2022
Deposit Date Nov 6, 2022
Publicly Available Date Nov 7, 2022
Journal Cardiovascular Diabetology
Print ISSN 1475-2840
Electronic ISSN 1475-2840
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 21
Issue 1
Article Number 202
Keywords Type 2 diabetes; Hypoglycemia; Platelet-associated proteins; Inflammation
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© The Author(s) 2022. <br /> Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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