PDF herunterladen
Hamostaseologie
DOI: 10.1055/s-0044-1780535
Original Article

Type 2 Diabetes: Platelets and Long-Term Metabolic Control as Estimated from Glycosylated Haemoglobin (HbA1c)

M. Edvardsson
1   Local Healthcare Centre, Finspång, Sweden
2   Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
,
M. Oweling
1   Local Healthcare Centre, Finspång, Sweden
,
P. Järemo
1   Local Healthcare Centre, Finspång, Sweden
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

In type 2 diabetes, platelets are likely affected by impaired long-term glycaemic control, but such pathophysiological links are poorly understood. This study thus compares platelet reactivity (i.e. agonist-evoked platelet reactions) in vitro with glycosylated haemoglobin (HbA1c), a measure commonly used for monitoring long-term metabolic control of type 2 diabetes. Elders with type 2 diabetes (n = 35) were divided according to HbA1c into groups (HbA1c—low and high) consisting of 17 and 18 subjects, respectively. For estimating mitochondria disintegration, a flow cytometer determined mitochondrial transmembrane potentials after whole blood agonist stimulation. The activating agents used were α-thrombin (10 μM) and collagen (0.15 μg/mL). The same apparatus analysed the fibrinogen receptor activity, lysosomal exocytosis (surface lysosomal-associated membrane protein 1), and platelet procoagulant characteristics (membrane-attached annexin V) after stimulation. In type 2 diabetes, after in vitro agonist stimulation, platelet mitochondria injury was higher in the HbA1c-high group. The fibrinogen receptor, lysosomal secretion, and the creation of procoagulant platelets proved to be uninfluenced by HbA1c.

Keywords

annexin V - αIIbβ3 activity - type 2 diabetes - HbA1c - lysosomal-associated membrane protein 1 - mitochondria - platelets - platelet reactivity

Raw Data

Data are available from the corresponding author upon reasonable request.


Authors' Contribution

M.E.: Conceived the research, performed sample and data collection, and did the practical flow cytometry work.


M.O.: Formulated and partly financed the investigation and supervised its findings.


P.J.: Devised and partially financed the study, carried out data analysis, and wrote the first draft of the manuscript. Subsequently, all authors revised the manuscript critically for intellectual content.




Publikationsverlauf

Eingereicht: 07. Oktober 2023

Angenommen: 08. Januar 2024

Artikel online veröffentlicht:
06. März 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Gaiz A, Mosawy S, Colson N, Singh I. Thrombotic and cardiovascular risks in type two diabetes; role of platelet hyperactivity. Biomed Pharmacother 2017; 94: 679-686
    CrossrefPubMedGoogle Scholar
  • 2 Pretorius L, Thomson GJA, Adams RCM, Nell TA, Laubscher WA, Pretorius E. Platelet activity and hypercoagulation in type 2 diabetes. Cardiovasc Diabetol 2018; 17 (01) 141
    CrossrefPubMedGoogle Scholar
  • 3 Tang WH, Stitham J, Jin Y. et al. Aldose reductase-mediated phosphorylation of p53 leads to mitochondrial dysfunction and damage in diabetic platelets. Circulation 2014; 129 (15) 1598-1609
    CrossrefPubMedGoogle Scholar
  • 4 Giannella A, Ceolotto G, Radu CM. et al. PAR-4/Ca2+-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes. Cardiovasc Diabetol 2021; 20 (01) 77
    CrossrefPubMedGoogle Scholar
  • 5 Ding Q, Wang F, Guo X, Liang M. The relationship between mean platelet volume and metabolic syndrome in patients with type 2 diabetes mellitus: a retrospective study. Medicine (Baltimore) 2021; 100 (13) e25303
    CrossrefPubMedGoogle Scholar
  • 6 Zhang Y, Zhou H. Hyper-reactive platelets and type 2 diabetes. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2022; 47 (03) 374-383
    PubMedGoogle Scholar
  • 7 Järemo P, Milovanovic M, Lindahl TL, Richter A. Elevated platelet density and enhanced platelet reactivity in stable angina pectoris complicated by diabetes mellitus type II. Thromb Res 2009; 124 (03) 373-374
    CrossrefPubMedGoogle Scholar
  • 8 Jastrzebska M, Lisman D, Szelepajlo A. et al. Evaluation of platelet reactivity during combined antiplatelet therapy in patients with stable coronary artery disease in relation to diabetes type 2 and the GPIIB/IIIA receptor gene polymorphism. J Physiol Pharmacol 2019;70(02):
    PubMedGoogle Scholar
  • 9 Järemo P. Computerised method for recording platelet density distribution. Eur J Haematol 1995; 54 (05) 304-309
    CrossrefPubMedGoogle Scholar
  • 10 Järemo P, Milovanovic M, Nilsson S, Buller C, Winblad B. Platelet heterogeneity and Alzheimer's disease: low density platelets populations demonstrate low in vivo activity. Platelets 2012; 23 (02) 116-120
    CrossrefPubMedGoogle Scholar
  • 11 Edvardsson M, Oweling M, Järemo P. Small procoagulant platelets in diabetes type 2. Thromb Res 2020; 195: 1-7
    CrossrefPubMedGoogle Scholar
  • 12 Corash L, Costa JL, Shafer B, Donlon JA, Murphy D. Heterogeneity of human whole blood platelet subpopulations. III. Density-dependent differences in subcellular constituents. Blood 1984; 64 (01) 185-193
    CrossrefPubMedGoogle Scholar
  • 13 Chamberlain KG, Seth P, Jones MK, Penington DG. Subcellular composition of platelet density subpopulations prepared using continuous Percoll gradients. Br J Haematol 1989; 72 (02) 199-207
    CrossrefPubMedGoogle Scholar
  • 14 Chamberlain KG, Penington DG. Monoamine oxidase and other mitochondrial enzymes in density subpopulations of human platelets. Thromb Haemost 1988; 59 (01) 29-33
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 15 Milovanovic M, Lysen J, Ramström S, Lindahl TL, Richter A, Järemo P. Identification of low-density platelet populations with increased reactivity and elevated alpha-granule content. Thromb Res 2003; 111 (1-2): 75-80
    CrossrefPubMedGoogle Scholar
  • 16 Milovanovic M, Lotfi K, Lindahl TL, Hallert C, Järemo P. Platelet density subpopulations in essential thrombocythemia and healthy volunteers. Pathophysiol Haemost Thromb 2010; 37 (01) 35-42
    CrossrefPubMedGoogle Scholar
  • 17 Södergren AL, Ramström S. Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol. Sci Rep 2018; 8 (01) 1441
    CrossrefPubMedGoogle Scholar
  • 18 Chu Y, Guo H, Zhang Y, Qiao R. Procoagulant platelets: generation, characteristics, and therapeutic target. J Clin Lab Anal 2021; 35 (05) e23750
    CrossrefPubMedGoogle Scholar
  • 19 Lugo-Gavidia LM, Carnagarin R, Burger D. et al. Circulating platelet-derived extracellular vesicles correlate with night-time blood pressure and vascular organ damage and may represent an integrative biomarker of vascular health. J Clin Hypertens (Greenwich) 2022; 24 (06) 738-749
    CrossrefPubMedGoogle Scholar
  • 20 Zhou R, Bozbas E, Allen-Redpath K, Yaqoob P. Circulating extracellular vesicles are strongly associated with cardiovascular risk markers. Front Cardiovasc Med 2022; 9 (09) 907457
    CrossrefPubMedGoogle Scholar
  • 21 Stone AP, Nikols E, Freire D, Machlus KR. The pathobiology of platelet and megakaryocyte extracellular vesicles: a (c)lot has changed. J Thromb Haemost 2022; 20 (07) 1550-1558
    CrossrefPubMedGoogle Scholar
  • 22 Santilli F, Marchisio M, Lanuti P, Boccatonda A, Miscia S, Davì G. Microparticles as new markers of cardiovascular risk in diabetes and beyond. Thromb Haemost 2016; 116 (02) 220-234
    PubMedGoogle Scholar
  • 23 Przygodzki T, Luzak B, Kassassir H. et al. Diabetes and hyperglycemia affect platelet GPIIIa expression. Effects on adhesion potential of blood platelets from diabetic patients under in vitro flow conditions. Int J Mol Sci 2020; 21 (09) 3222
    CrossrefPubMedGoogle Scholar
  • 24 Tay HM, Leong SY, Xu X. et al. Direct isolation of circulating extracellular vesicles from blood for vascular risk profiling in type 2 diabetes mellitus. Lab Chip 2021; 21 (13) 2511-2523
    CrossrefPubMedGoogle Scholar
  • 25 Nomura S. Microparticle and atherothrombotic diseases. J Atheroscler Thromb 2016; 23 (01) 1-9
    CrossrefPubMedGoogle Scholar
  • 26 Ravera S, Signorello MG, Panfoli I. Platelet metabolic flexibility: a matter of substrate and location. Cells 2023; 12 (13) 1802
    CrossrefPubMedGoogle Scholar
  • 27 Sowton AP, Millington-Burgess SL, Murray AJ, Harper MT. Rapid kinetics of changes in oxygen consumption rate in thrombin-stimulated platelets measured by high-resolution respirometry. Biochem Biophys Res Commun 2018; 503 (04) 2721-2727
    CrossrefPubMedGoogle Scholar
  • 28 Tamura N, Goto S, Yokota H, Goto S. Contributing role of mitochondrial energy metabolism on platelet adhesion, activation and thrombus formation under blood flow conditions. Platelets 2022; 33 (07) 1083-1089
    CrossrefPubMedGoogle Scholar
  • 29 Guo X, Wu J, Du J, Ran J, Xu J. Platelets of type 2 diabetic patients are characterized by high ATP content and low mitochondrial membrane potential. Platelets 2009; 20 (08) 588-593
    CrossrefPubMedGoogle Scholar
  • 30 Siewiera K, Labieniec-Watala M, Kassassir H, Wolska N, Polak D, Watala C. Potential role of mitochondria as modulators of blood platelet activation and reactivity in diabetes and effect of metformin on blood platelet bioenergetics and platelet activation. Int J Mol Sci 2022; 23 (07) 3666
    CrossrefPubMedGoogle Scholar
  • 31 Wu F, Liu Y, Luo L. et al. Platelet mitochondrial dysfunction of DM rats and DM patients. Int J Clin Exp Med 2015; 8 (05) 6937-6946
    PubMedGoogle Scholar
  • 32 Xin G, Wei Z, Ji C. et al. Metformin uniquely prevents thrombosis by inhibiting platelet activation and mtDNA release. Sci Rep 2016; 6: 36222
    CrossrefPubMedGoogle Scholar