Platelet aggregation is not altered among men with diabetes mellitus

  • Christian KringEmail author
  • Lars M. Rasmussen
  • Jes S. Lindholt
  • Axel C. P. Diederichsen
  • Pernille J. Vinholt
Original Article



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.


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.


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.


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



Atherosclerosis Platelet aggregation Diabetes mellitus Light transmission aggregometry Coronary artery calcification 



Adenosine diphosphate


Agatston units


Coronary artery calcification


Cardiovascular disease


Hemoglobin A1c


High-density lipoprotein


Interquartile range


Low-density lipoprotein


Light transmission aggregometry


Protease-activated receptor-4


Platelet-poor plasma


Platelet-rich plasma


Thrombin receptor-activating peptide



The authors thank the entire staff of DANCAVAS.

Author contributions

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.


The study received research support from Odense University Hospital and from the Hansen-Bille Braheske Family foundation.

Compliance with ethical standards

Conflict of interest

The author declares that they have no conflict of interest.

Ethical standards disclosure

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.

Informed consent disclosure

All persons gave written informed consent.

Availability of data and material

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

592_2019_1438_MOESM1_ESM.tif (125 kb)
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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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Biochemistry and PharmacologyOdense University HospitalOdense CDenmark
  2. 2.Centre of Individualized Medicine in Arterial Disease (CIMA)OdenseDenmark
  3. 3.Department of Cardiothoracic and Vascular SurgeryOdense University HospitalOdenseDenmark
  4. 4.Department of CardiologyOdense University HospitalOdenseDenmark

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