Diabetes mellitus and hemostasis. Intrigue of relationships. Part 1. Endothelial dysfunction
https://doi.org/10.14341/DM13217
Abstract
This literature review is the first in a series of articles devoted to the mutual influence of diabetes mellitus (DM) and hemostatic disorders associated with endothelial dysfunction (ED), changes in platelet activity, plasma-coagulation link of hemostasis, activity of natural anticoagulants and fibrinolysis. The main mechanisms of development of ED, the possibilities of its detection not only in scientific research, but also in routine clinical practice are analyzed. The main principles of both non-drug and drug correction of ED are also given. Emphasis is placed on the possibility of using for this purpose drugs with and without a hypoglycemic effect. An opinion is expressed about the presence of a reverse effect of ED on the imbalance of carbohydrate metabolism, which, in the opinion of the authors, can significantly expand the understanding of the role of these disorders not only in the development of complications, but also in the pathogenesis of diabetes mellitus itself.
About the Authors
G. A. Berezovskaya
Pavlov First Saint Petersburg State Medical University
Russian Federation
Competing Interests:
Russian Federation
Gelena A. Berezovskaya - MD, PhD, Associate Professor; ResearcherID: KYR-9204-2024; Scopus Author ID: 56700397600; eLibrary SPIN: 3931-3943.
6-8 Lva Tolstogo street, 197022 Saint Petersburg
Competing Interests:
none
N. N. Petrishchev
Pavlov First Saint Petersburg State Medical University
Russian Federation
Competing Interests:
Russian Federation
Nikolai N. Petrishchev, MD, PhD, Professor; ResearcherID: H-9236-2019; Scopus Author ID: 7005080867; eLibrary SPIN: 7377-2565.
Saint Petersburg
Competing Interests:
none
Yu. Sh. Khalimov
Pavlov First Saint Petersburg State Medical University
Russian Federation
Competing Interests:
Russian Federation
Yuri Sh. Khalimov - MD, PhD; ResearcherID: AFG-7640-2022; Scopus Author ID: 55531165300; eLibrary SPIN: 7315-6746; РИНЦ ID: 464335
Saint Petersburg
Competing Interests:
none
References
1. Carrizzo A, Izzo C, Oliveti M, et al. The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial Dysfunction and Platelet Hyperaggregation. International Journal of Molecular Sciences. 2018;19(10):2968. doi: https://doi.org/10.3390/ijms19102968
2. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. doi: https://doi.org/10.1016/j.diabres.2019.107843
3. Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017;389(10085):2239-2251. doi: https://doi.org/10.1016/S0140-6736(17)30058-2
4. Yuen L, Saeedi P, Riaz M, et al. Projections of the prevalence of hyperglycaemia in pregnancy in 2019 and beyond: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107841. doi: https://doi.org/10.1016/j.diabres.2019.107841
5. Ge Y, He D, Shao Y, Wang L, Yan W. Percutaneous coronary intervention in insulin-treated diabetic patients: A meta-analysis. Ann Noninvasive Electrocardiol. 2022;27(5):e12953. doi: https://doi.org/10.1111/anec.12953
6. Liu H, Wang X, Gao H, et al. Physiological and pathological characteristics of vascular endothelial injury in diabetes and the regulatory mechanism of autophagy. Front Endocrinol (Lausanne). 2023;14:1191426. doi: https://doi.org/10.3389/fendo.2023.1191426
7. Lin S, Rocha VM, Taylor R. Artefactual inflation of type 2 diabetes prevalence in WHO STEP surveys. Trop Med Int Health. 2019;24(4):477-483. doi: https://doi.org/10.1111/tmi.13213
8. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. doi: https://doi.org/10.1016/j.diabres.2021.109119
9. Nations U. World population prospects: the 2017 revision, key findings and advance tables. Department of Economics and Social Affairs PD, editor. New York: United Nations. 2017;46
10. Jovanovic L, Rajkovic M, Subota V, et al. Predictive value of admission glycemia in diabetics with pulmonary embolism compared to non-diabetic patients. Acta Diabetol. 2022;59(5):653-659. doi: https://doi.org/10.1007/s00592-021-01843-2
11. Bryk-Wiązania AH, Undas A. Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation. Cardiovasc Diabetol. 2021;20(1):191. doi: https://doi.org/10.1186/s12933-021-01372-w
12. Elrakaybi A, Laubner K, Zhou Q, et al. Cardiovascular protection by SGLT2 inhibitors - Do anti-inflammatory mechanisms play a role? Mol Metab. 2022;64:101549. doi: https://doi.org/10.1016/j.molmet.2022.101549
13. Dang Z, Avolio E, Thomas AC, et al. Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signalling pathway. Eur J Heart Fail. 2020;22(9):1568-1581. doi: https://doi.org/10.1002/ejhf.1840
14. Izoe Y, Nagao M, Sato K, et al. Dynamic coronary CT Angiography-Estimated coronary flow in Non-Obstructive, Plaque-free coronary Arteries: Association with dyslipidemia and diabetes. Int J Cardiol Heart Vasc. 2022;42:101098. doi: https://doi.org/10.1016/j.ijcha.2022.101098
15. Garcia-Sayan E, Lee M, Stone JR, et al. Endothelial Dysfunction and Cardiometabolic Risk Factors in Mexican American Adults: The Cameron County Hispanic Cohort. Am J Cardiol. 2023;205:75-83. doi: https://doi.org/10.1016/j.amjcard.2023.07.165
16. Hung MJ, Chang NC, Hu P, et al. Association between Coronary Artery Spasm and the risk of incident Diabetes: A Nationwide population-based Cohort Study. Int J Med Sci. 2021;18(12):2630-2640. doi: https://doi.org/10.7150/ijms.57987
17. Bhatti JS, Sehrawat A, Mishra J, et al. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic Biol Med. 2022;184:114-134. doi: https://doi.org/10.1016/j.freeradbiomed.2022.03.019
18. Huang Y, Yue L, Qiu J, et al. Endothelial Dysfunction and Platelet Hyperactivation in Diabetic Complications Induced by Glycemic Variability. Horm Metab Res. 2022;54(7):419-428. doi: https://doi.org/10.1055/a-1880-0978
19. Jalilian E, Elkin K, Shin SR. Novel Cell-Based and Tissue Engineering Approaches for Induction of Angiogenesis as an Alternative Therapy for Diabetic Retinopathy. Int J Mol Sci. 2020;21(10):3496. doi: https://doi.org/10.3390/ijms21103496
20. Benítez-Camacho J, Ballesteros A, Beltrán-Camacho L, et al. Endothelial progenitor cells as biomarkers of diabetes-related cardiovascular complications. Stem Cell Res Ther. 2023;14(1):324. doi: https://doi.org/10.1186/s13287-023-03537-8
21. Zhao N, Yu X, Zhu X, et al. Diabetes Mellitus to Accelerated Atherosclerosis: Shared Cellular and Molecular Mechanisms in Glucose and Lipid Metabolism. J Cardiovasc Transl Res. 2024;17(1):133-152. doi: https://doi.org/10.1007/s12265-023-10470-x
22. Li S, Deng J, Sun D, et al. FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition. Redox Biol. 2022;58:102530. doi: https://doi.org/10.1016/j.redox.2022.102530
23. Masola V, Zaza G, Arduini A, et al. Endothelial Glycocalyx as a Regulator of Fibrotic Processes. Int J Mol Sci. 2021;22(6):2996. doi: https://doi.org/10.3390/ijms22062996
24. Qiu Y, Buffonge S, Ramnath R, et al. Endothelial glycocalyx is damaged in diabetic cardiomyopathy: angiopoietin 1 restores glycocalyx and improves diastolic function in mice. Diabetologia. 2022;65(5):879-894. doi: https://doi.org/10.1007/s00125-022-05650-4
25. Ramnath RD, Butler MJ, Newman G, et al. Blocking matrix metalloproteinase-mediated syndecan-4 shedding restores the endothelial glycocalyx and glomerular filtration barrier function in early diabetic kidney disease. Kidney Int. 2020;97(5):951-965. doi: https://doi.org/10.1016/j.kint.2019.09.035
26. Kaur G, Harris NR. Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy. Am J Physiol Cell Physiol. 2023;324(5):C1061-C1077. doi: https://doi.org/10.1152/ajpcell.00188.2022
27. Ćurko-Cofek B, Jenko M, Taleska Stupica G, et al. The Crucial Triad: Endothelial Glycocalyx, Oxidative Stress, and Inflammation in Cardiac Surgery—Exploring the Molecular Connections. Int. J. Mol. Sci. 2024;25:10891. doi: https://doi.org/10.3390/ijms252010891
28. Zheng Y, Luo A, Liu X. The imbalance of mitochondrial Fusion/Fission drives high-Glucose-Induced vascular injury. Biomolecules. 2021;11:1779. doi: https://doi.org/10.3390/biom11121779
29. Vasina LV, Petrishchev NN, Vlasov TD. Markers of endothelial dysfunction. Regional blood circulation and microcirculation. 2017;16(1):4-15. (In Russ.) doi: https://doi.org/10.24884/1682-6655-2017-16-1-4-15
30. Matvienko OI, Namestnikov IA, Golovina OG, et al. Vklad mikrochastits v razvitie giperkoaguliatsionnogo sindroma u patsientov s posttromboticheskoi bolezniu. Vestnik gematologii. 2011;7(1):112-113. (In Russ.)
31. Matvienko OI, Namestnikov IA, Golovina OG, et al. Giperkoaguliatsionnyi sindrom pri ishemicheskom insulte. Klinicheskaia gerontologiia 2011;9-10:34-38. (In Russ.)
32. Petrishchev NN, Vasinа LV, Lugovaya AV. Content of soluble markers of apoptosis and circulating V annexin-connected apoptosistic cells in the blood of patients with acute coronary syndrome. Vestnik of Saint Petersburg University. 2008;11(1):14–23. (In Russ.)
33. Li FX, Xu F, Li CC, et al. Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles. Int J Nanomedicine. 2024;19:10077-10095. doi: https://doi.org/10.2147/IJN.S441847
34. Lee JH, Lee J. Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic β-Cell Dysfunction and Senescence in Type 2 Diabetes. Int J Mol Sci. 2022;23(9):4843. doi: https://doi.org/10.3390/ijms23094843
35. Kudo T, Zhao ML, Jeknić S, et al. Context-dependent regulation of lipid accumulation in adipocytes by a HIF1α-PPARγ feedback network. Cell Syst. 2023;14(12):1074-1086.e7. doi: https://doi.org/10.1016/j.cels.2023.10.010
36. Rodriguez-Rodriguez AE, Porrini E, Torres A. Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes? Int J Mol Sci. 2021;22(19):10311. doi: https://doi.org/10.3390/ijms221910311
37. Vlasova TI, Petrishchev NN, Vlasov TD. Endothelium and aging: mechanisms for formation of senescence associated phenotype of endothelial cells. Regional blood circulation and microcirculation. 2023;22(3):19–33. (In Russ.) doi: https://doi.org/10.24884/1682- 6655-2023-22-3-19-33
38. Liao YL, Fang YF, Sun JX, Dou GR. Senescent endothelial cells: a potential target for diabetic retinopathy. Angiogenesis. 2024;27(4):663-679. doi: https://doi.org/10.1007/s10456-024-09943-7
39. Donato AJ, Machin DR, Lesniewski LA. Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease. Circ Res. 2018;123(7):825-848. doi: https://doi.org/10.1161/CIRCRESAHA.118.312563
40. Akrivou D, Perlepe G, Kirgou P, et al. Pathophysiological Aspects of Aging in Venous Thromboembolism: An Update. Medicina (Kaunas). 2022;58(8):1078. doi: https://doi.org/10.3390/medicina58081078
41. McCafferty C, Busuttil-Crellin X, Cai T, et al. Plasma Proteomic Analysis Reveals Age-Specific Changes in Platelet- and Endothelial Cell-Derived Proteins and Regulators of Plasma Coagula tion and Fibrinolysis. J Pediatr. 2020;221S:S29-S36. doi: https://doi.org/10.1016/j.jpeds.2020.01.051
42. Yu Y, Li W, Xu L, Wang Y. Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes. Front Endocrinol (Lausanne). 2023;14:1124353. doi: https://doi.org/10.3389/fendo.2023.1124353
43. Dmitrieva NI, Boehm M, Yancey PH, Enhörning S. Long-term health outcomes associated with hydration status. Nat Rev Nephrol. 2024;20(5):275-294. doi: https://doi.org/10.1038/s41581-024-00817-1
44. Alwafi H, Alsharif AA, Wei L, et al. Incidence and prevalence of hypoglycaemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2020;170:108522. doi: https://doi.org/10.1016/j.diabres.2020.108522
45. Manosroi W, Phimphilai M, Waisayanand N, et al. CORE-Thailand investigators. Glycated hemoglobin variability and the risk of cardiovascular events in patients with prediabetes and type 2 diabetes mellitus: A post-hoc analysis of a prospective and multicenter study. J Diabetes Investig. 2023;14(12):1391-1400. doi: https://doi.org/10.1111/jdi.14073
46. Kolb H, Kempf K, Röhling M, Martin S. Insulin: too much of a good thing is bad. BMC Med. 2020;18(1):224. doi: https://doi.org/10.1186/s12916-020-01688-6
47. Foreman YD, van Doorn WPTM, Schaper NC, et al. Greater daily glucose variability and lower time in range assessed with continuous glucose monitoring are associated with greater aortic stiffness: The Maastricht Study. Diabetologia. 2021;64(8):1880-1892. doi: https://doi.org/10.1007/s00125-021-05474-8
48. Hu Y, Li Z, Li H, et al. Severe hypoglycaemia-induced microglial inflammation damages microvascular endothelial cells, leading to retinal destruction. Diab Vasc Dis Res. 2024;21(4):1-11. doi: https://doi.org/10.1177/14791641241278506
49. Choi SY, Ko SH. Severe hypoglycemia as a preventable risk factor for cardiovascular disease in patients with type 2 diabetes mellitus. Korean J Intern Med. 2021;36(2):263-270. doi: https://doi.org/10.3904/kjim.2020.327
50. Kusunoki Y, Konishi K, Tsunoda T, Koyama H. Significance of Glycemic Variability in Diabetes Mellitus. Intern Med. 2022;61(3):281-290. doi: https://doi.org/10.2169/internalmedicine.8424-21
51. Balta S. Endothelial Dysfunction and Inflammatory Markers of Vascular Disease. Curr Vasc Pharmacol. 2021;19(3):243-249. doi: https://doi.org/10.2174/1570161118666200421142542
52. Naumov AV, Prokofieva TV, Polunina OS, et al. Analysis of annexin V levels and cytokine status in patients with acute myocardial infarction. Medical alphabet. 2022;(19):33-38. (In Russ.) doi: https://doi.org/10.33667/2078-5631-2022-19-33-38
53. Khripun IA, Morgunov MN, Vorobev SV, i dr. Endotelialnaia disfunktsiia i sakharnyi diabet 2 tipa: novye markery rannei diagnostiki. Kardiovaskuliarnaia terapiia i profilaktika. 2016;15(5):59-63. (In Russ.) doi: http://dx.doi.org/10.15829/1728-8800-2016-5-59-63
54. Gao J, Pan X, Li G, et al. Physical Exercise Protects Against Endothelial Dysfunction in Cardiovascular and Metabolic Diseases. J Cardiovasc Transl Res. 2022;15(3):604-620. doi: https://doi.org/10.1007/s12265-021-10171-3
55. Khalimov IS, Rubtsov IE, Salukhov VV, Agafonov PV. Inhibitors of the sodium-glucose transporter type 2 and new possibilities for managing vascular age in patients with type 2 diabetes mellitus. Medical Council. 2021;12:228-236. (In Russ.) doi: https://doi.org/10.21518/2079-701X-2021-12-228-236
56. Nedosugova LV, Markina YV, Bochkareva LA, et al. Inflammatory Mechanisms of Diabetes and Its Vascular Complications. Biomedicines. 2022;10(5):1168. doi: https://doi.org/10.3390/biomedicines10051168
Supplementary files
Review
For citations:
Berezovskaya G.A., Petrishchev N.N., Khalimov Yu.Sh. Diabetes mellitus and hemostasis. Intrigue of relationships. Part 1. Endothelial dysfunction. Diabetes mellitus. 2025;28(4):376-383. (In Russ.) https://doi.org/10.14341/DM13217
Views:
19
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
