Abstract
Aims
Platelets are pivotal in arterial thrombosis, and platelet hyperresponsiveness may contribute to the increased incidence of cardiovascular events in diabetes mellitus. Consequently, we hypothesized that increased in vitro platelet aggregation responses exist in men with diabetes mellitus.
Methods
The Danish Cardiovascular Screening Trial (DANCAVAS) is a community-based cardiovascular screening trial including men aged 65–74 years. Platelet aggregation was tested using 96-well light transmission aggregometry with thrombin receptor-activating peptide (TRAP), adenosine diphosphate, collagen type 1, arachidonic acid and protease-activated receptor-4 in three concentrations. Further, cardiovascular risk factors and coronary artery calcification (CAC), estimated by CT scans and ankle–brachial index, were obtained.
Results
Included were 720 men aged 65–74 years, 110 with diabetes mellitus. Overall, there was no difference in platelet aggregation among men with versus without diabetes mellitus when adjusting for or excluding platelet inhibitor treatment and men with established cardiovascular disease (CVD). This was true for all agonists, e.g., 10 µM TRAP-induced platelet aggregation of median 69% (IQR 53–75) versus 70% (IQR 60–76) in men with versus without diabetes mellitus. Platelet aggregation did not correlate with HbA1c or CAC. Men with diabetes mellitus displayed higher CAC, median 257 Agatston units (IQR 74–1141) versus median 111 Agatston units (IQR 6–420) in the remaining individuals, p < 0.0001.
Conclusions
Among outpatients with diabetes mellitus, but no CVD and no platelet inhibitor treatment, neither are platelets hyperresponsive in diabetes mellitus, nor is platelet aggregation associated with glycemic status or with the degree of coronary atherosclerosis.
Trial Registration
ISRCTN12157806.
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Abbreviations
- ADP:
-
Adenosine diphosphate
- AU:
-
Agatston units
- CAC:
-
Coronary artery calcification
- CVD:
-
Cardiovascular disease
- HbA1c :
-
Hemoglobin A1c
- HDL:
-
High-density lipoprotein
- IQR:
-
Interquartile range
- LDL:
-
Low-density lipoprotein
- LTA:
-
Light transmission aggregometry
- PAR-4:
-
Protease-activated receptor-4
- PPP:
-
Platelet-poor plasma
- PRP:
-
Platelet-rich plasma
- TRAP:
-
Thrombin receptor-activating peptide
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Acknowledgements
The authors thank the entire staff of DANCAVAS.
Funding
The study received research support from Odense University Hospital and from the Hansen-Bille Braheske Family foundation.
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CK contributed to study design, research, analysis and interpretation of the data, and writing of the manuscript. LMR contributed to study design, interpretation of the data and editing of the manuscript. JSL contributed to study design, interpretation of the data and editing of the manuscript. ACPD contributed to study design, interpretation of the data and editing of the manuscript. PJV contributed to study design, data analysis and interpretation of the data, and editing of the manuscript. CK is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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The study was approved by the Danish Data Protection Agency (16/18852) and the Regional Scientific Ethical Committees of Southern Denmark (S-20140028). The study was conducted in accordance with the guidelines of the Helsinki Declaration.
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Supplemental Fig. 1
Coronary artery calcification in patients with and without diabetes mellitus. Coronary artery calcification was determined from low-dose CT scans without contrast of the coronary arteries. Box plots show coronary artery calcification in men with (n = 66) and without (n = 476) diabetes mellitus after exclusion of men treated with platelet inhibitors. Horizontal line indicates median, boxes reflect interquartile range and whiskers are 10th and 90th percentiles. Dots are individual values above the 90th percentile. Men with cardiovascular disease were excluded. p value were generated by Mann–Whitney U test. AU: Agatston units; CAC: coronary artery calcification (TIFF 124 kb)
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Kring, C., Rasmussen, L.M., Lindholt, J.S. et al. Platelet aggregation is not altered among men with diabetes mellitus. Acta Diabetol 57, 389–399 (2020). https://doi.org/10.1007/s00592-019-01438-y
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DOI: https://doi.org/10.1007/s00592-019-01438-y