Endocrinology
doi: 10.25005/2074-0581-2026-28-2-445-453
MARKERS OF ENDOTHELIAL DYSFUNCTION IN CHILDREN WITH TYPE 1 DIABETES MELLITUS
1Stavropol State Medical University, Stavropol, Russian Federation
2Children's City Clinical Hospital named after G.K. Filippsky, Stavropol, Russian Federation
3Regional Children's Clinical Hospital, Stavropol, Russian Federation
Objective: To assess the serum levels of markers of endothelial glycocalyx (EG) degradation in children with type 1 diabetes mellitus (T1DM), depending on the presence or absence of diabetic complications, in order to determine the severity of endothelial dysfunction (ED).
Methods: A total of 60 children and adolescents were examined (median age 7 [3; 16] years), 30 of whom formed the main group (patients with T1DM; MG), while the other 30 were included in the control group (CG). Depending on the presence or absence of diabetic complications (neuro-, retinopathy, and nephropathy), patients from the MG were divided into two subgroups: those without complications (n=16) and those with complications (n=14). In all children, serum markers of EG degradation were determined by enzyme-linked immunosorbent assay: syndecan-1 (SDC1), syndecan-4 (SDC4), endocan-1 (EC1), heparan sulfate (HS), angiopoietin-1 (AP1), and hyaluronic acid (HA).
Results: Four out of six studied markers of EGL degradation – SDC4, HS, AP1, and HA – were elevated in the serum of patients with MG compared with children in the CG. The concentrations of SDC1 and EC1 in patients with T1DM did not differ significantly from those in the control group. The highest serum levels of SDC1, SDC4, HS, and HA were found in patients with T1DM who had diabetic complications. No statistically significant differences were found in the increase in EC1 and AP1 concentrations between children with diabetic complications and apparently healthy children.
Conclusion: High serum levels of SDC4, HS, AP1, and HA in children with T1DM indicate EG degradation and ED. Elevated concentrations of SDC1, SDC4, HS, and HA may serve as laboratory criteria for the presence of diabetic complications.
Keywords: Type 1 diabetes mellitus, children and adolescents, endothelial dysfunction, glycocalyx, diabetic complications.
References
- Rajabloo Y, Saberi-Karimian M, Soflaei SS, Ferns GA, Ghayour-Mobarhan M. Syndecans and diabetic complications: A narrative review. Am J Med Sci. 2024;368(2):99-111. https://doi.org/10.1016/j.amjms.2024.04.017
- Buchmann M, Tuncer O, Auzanneau M, Eckert AJ, Rosenbauer J, Reitzleet L, et al. Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation. J Health Monit. 2023;8(2):57-78. https://doi.org/10.25646/11439.2
- Kandemir N, Vuralli D, Ozon A, Gonc N, Ardicli D, Jalilova L, et al. Epidemiology of type 1 diabetes mellitus in children and adolescents: A 50-year, single-cen- ter experience. J Diabetes. 2024;16(5):e13562. https://doi.org/10.1111/1753- 0407.13562
- Longendyke R, Grundman JB, Majidi S. Acute and chronic adverse outcomes of type 1 diabetes. Endocrinol Metab Clin North Am. 2024;53(1):123-33. https:// doi.org/10.1016/j.ecl.2023.09.004
- Khalaji A, Behnoush AH, Saeedian B, Khanmohammadi S, Shokri Varniab Z, Pei- man S. Endocan in prediabetes, diabetes, and diabetes-related complications: A systematic review and meta-analysis. Diabetol Metab Syndr. 2023;15:102. https://doi.org/10.1186/s13098-023-01076-z
- Lespagnol E, Dauchet L, Pawlak-Chaouch M, Balestra C, Berthoin S, Feelischet M, et al. Early endothelial dysfunction in type 1 diabetes is accompanied by an im- pairment of vascular smooth muscle function: A meta-analysis. Front Endocrinol (Lausanne). 2020;11:203. https://doi.org/10.3389/fendo.2020.00203
- Giuliani A, Ramini D, Sbriscia M, Crocco P, Tiano L, Rippo MR, et al. Syndecan 4 is a marker of endothelial inflammation in pathological aging and predicts long-term cardiovascular outcomes in type 2 diabetes. Diabetol Metab Syndr. 2024;16(1):203. https://doi.org/10.1186/s13098-024-01431-8
- Vorobyova AP, Bykov YuV, Baturin VA, Massorov VV. Rol' glikokaliksa v pato- geneze oslozhneniy sakharnogo diabeta [The role of glycocalyx in the pathogen- esis of complications of diabetes mellitus.]. Zabaykal'skiy meditsinskiy vestnik. 2024;2:80-9. https://doi.org/10.52485/19986173_2024_2_80.
- Vorobyova AP, Bykov YuV, Baturin VA, Muravyova A.A. Markyory povrezhdeniya glikokaliksa pri oslozhneniyakh sakharnogo diabeta [Markers of glycocalyx dam- age in complications of diabetes mellitus.]. Sovremennye problemy nauki i obra- zovaniya. 2023;4. https://doi.org/10.17513/spno.32783
- Patterson EK, Cepinskas G, Fraser DD. Endothelial glycocalyx degradation in critical illness and injury. Front Med (Lausanne). 2022;9:898592. https://doi. org/10.3389/fmed.2022.898592
- Li J, Qi Z, Sun C, Gong L, Li Y, Donget H, et al. Circulating glycocalyx shedding products as biomarkers for evaluating prognosis of patients with out-of-hospital cardiac arrest after return of spontaneous circulation. Sci Rep. 2024;14(1):17582. https://doi.org/10.1038/s41598-024-68738-4
- Kakutani Y, Morioka T, Yamazaki Y, Ochi A, Fukumoto S, Shoji T, et al. Asso- ciation of serum syndecan-1 concentrations with albuminuria in type 2 di- abetes. Diab Vasc Dis Res. 2024;21(4):14791641241278362. https://doi. org/10.1177/14791641241278362
- Agere SA, Kim EY, Akhtar N, Ahmed S. Syndecans in chronic inflammatory and autoimmune diseases: Pathological insights and therapeutic opportunities. J Cell Physiol. 2018;233(9):6346-58. https://doi.org/10.1002/jcp.26388
- Hiebert LM. Heparan sulfate proteoglycans in diabetes. Semin Thromb Hemost. 2021;47(3):261-73. https://doi.org/10.1055/s-0041-1724118
- Li SB, Zou HQ, Gong MM, Chen YQ, Yan XY, Yu LM, et al. Angiopoietin-1 pro- motes the integrity of neovascularization in the subcutaneous matrigel of type 1 diabetic rats. Biomed Res Int. 2019:2019:2016972. https://doi. org/10.1155/2019/2016972
- Butler AE, Al-Qaissi A, Sathyapalan T, Atkin SL. Angiopoietin-1: An early bio- marker of diabetic nephropathy? J Transl Med. 2021;19(1):427. https://doi. org/10.1186/s12967-021-03105-9
- Lim J, Machin DR, Donato AJ. The role of hyaluronan in endothelial glycocalyx and potential preventative lifestyle strategy with advancing age. Curr Top Membr. 2023;91:139-56. https://doi.org/10.1016/bs.ctm.2023.02.006
- Nagy N, Sunkari VG, Kaber G, Hasbun S, Lam DN, Speakeet, C et al. Hyaluro- nan levels are increased systemically in human type 2 but not type 1 diabetes independently of glycemic control. Matrix Biol. 2019;80:46-58. https://doi. org/10.1016/j.matbio.2018.09.003
- Knežević D, Ćurko-Cofek D, Batinac T, Laškarin G, Rakić M, Šoštarič M, et al. Endothelial dysfunction in patients undergoing cardiac surgery: A narrative re- view and clinical implications. J Cardiovasc Dev Dis. 2023;10(5):213. https://doi. org/10.3390/jcdd10050213
- Kaur G, Rogers J, Rashdan NA, Cruz-Topete D, Pattillo CB, Hartson SD, et al. Hyper- glycemia-induced effects on glycocalyx components in the retina. Exp Eye Res. 2021;213:108846. https://doi.org/10.1016/j.exer.2021
- Lauer ME, Hascall VC, Wang A. Heparan sulfate analysis from diabetic rat glomer- uli. J Biol Chem. 2007;282(2):843-52. https://doi.org/10.1074/jbc.M608823200
- Moretto P, Karousou E, Viola M, Caon I, Luisa D'Angelo M, De Luca G, et al. Regu- lation of hyaluronan synthesis in vascular diseases and diabetes. J Diabetes Res. 2015:2015:167283. https://doi.org/10.1155/2015/167283
- Nieuwdorp M, Holleman F, de Groot E, Vink H, Gort J, Kontush A, et al. Pertur- bation of hyaluronan metabolism predisposes patients with type 1 diabetes mellitus to atherosclerosis. Diabetologia. 2007;50(6):1288-93. https://doi. org/10.1007/s00125-007-0666-4
- McDonald TO, Gerrity RG, Jen C, Chen HJ, Wark K, Wight TN, et al. Diabetes and arterial extracellular matrix changes in a porcine model of atherosclero- sis. J Histochem Cytochem. 2007;55(11):1149-57. https://doi.org/10.1369/ jhc.7A7221.2007
- Wang A, de la Motte C, Lauer M, Hascall V. Hyaluronan matrices in pathobio- logical processes. FEBS Journal. 2011;278(9):1412-8. https://doi.org/10.1111/ j.1742-4658.2011.08069.x
Authors' information:
Aksyonova Yulia Sergeevna,
Undergraduate Student of Stavropol State Medical University
ORCID ID: 0009-0000-0244-1377
E-mail: iu.axenowa2015@yandex.ru
Vorobyova Anna Pavlovna,
Anesthesiologist-reanimatologist, Children's City Clinical Hospital named after G.K. Filippsky
ORCID ID: 0000-0002-0082-1971
E-mail: a.v.955@yandex.ru
Bykov Yuriy Vitalievich,
Candidate of Medical Sciences, Associate Professor of the Department of Anesthesiology and Intensive Care with a Course of Additional Professorial Education, Stavropol State Medical University; Anesthesiologist-Reanimatologist, Regional Children's Clinical Hospital
ORCID ID: 0000-0003-4705-3823
E-mail: yubykov@gmail.com
Baturin Vladimir Aleksandrovich,
Doctor of Medical Sciences, Full Professor, Head of the Department of Clinical Pharmacology with a Course of Additional Professorial Education, Stavropol State Medical University
ORCID ID: 0000-0002-6892-3552
E-mail: prof.baturin@gmail.com
Mаssorov Vladislav Viktorovich,
Anesthesiologist-Reanimatologist, Children's City Clinical Hospital named after G.K. Filippsky
ORCID ID: 0009-0008-4009-1783
E-mail: Vladislav.massorov@yandex.ru
Avakyan Georgiy Arturovich,
Undergraduate Student of Stavropol State Medical University
ORCID ID: 0009-0006-7630-5734
E-mail: nepsan54@gmail.com
Information about support in the form of grants, equipment, medications
The authors did not receive financial support from manufacturers of medicines and medical equipment
Conflicts of interest: No conflict
Address for correspondence:
Bykov Yuriy Vitalievich
Candidate of Medical Sciences, Associate Professor of the Department of An- esthesiology and Intensive Care with a Course of Additional Professorial Edu- cation, Stavropol State Medical University; Anesthesiologist-Reanimatologist, Regional Children's Clinical Hospital
355031, Russian Federation, Stavropol, Mira str., 310
Теl.: +7 (962) 4430492
E-mail: yubykov@gmail.com
This work is licensed under a Creative Commons Attribution 4.0 International License.
Materials on the topic:
- IODINE DEFICIENCY IN TAJIKISTAN: HISTORY, CURRENT REALITIES, AND POSSIBLE SOLUTIONS
- IMPACT OF CELEBRITY STATEMENTS ON INTERNET SEARCHES ON THE USE OF SEMAGLUTIDE FOR WEIGHT LOSS
- EPIDEMIOLOGICAL CHARACTERISTICS OF SUBCLINICAL HYPOTHYROIDISM
- EPIDEMIOLOGY OF PRIMARY HYPERPARATHYROIDISM
- DIAGNOSTIC AND TACTICAL ERRORS IN THE MANAGEMENT OF PATIENTS WITH PHEOCROMOCYTOMA
- AUTOIMMUNE POLYGLANDULAR SYNDROME PREVALENCE IN TOLUCA, MEXICO
- BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH TYPE 2 diabetes mellitus in THE HIGH FERTILITY REGION
- SOME ASPECTS OF METABOLIC CHANGES IN HYPERPROLACTINEMIA OF TUMOUR AND NON-TUMOUR GENESIS