THIOL/DISULPHIDE HOMEOSTASIS AND SALIVARY VASCULAR ENDOTELIAL GROWTH FACTOR LEVELS IN TYPE 1 DIABETIC CHILDREN WITH GINGIVITIS

Year 2024, Volume: 25 Issue: 4, 451 - 465

Sultan Keles , Ozge Cevik , Ahmet Anık , Ayşe Anık , Burcin Irem Abas

https://doi.org/10.69601/meandrosmdj.1596241

Abstract

Objective: To evaluate the thiol/disulphide homeostasis and level of vascular endothelial growth factor (VEGF) in saliva of children with type 1 diabetes mellitus and gingivitis.
Methodology: Forty children with type 1 diabetes mellitus [DM] and 40 systemically healthy [H]) children were recruited for the study. Based on children’ periodontal and systemic health status, they were divided into four subgroups: 1) systemically and periodontally healthy children (Hh), 2) systemically healthy children with gingivitis (Hg), 3) diabetic children with periodontal health (DM+h), and 4) diabetic children with gingivitis (DM+g). Periodontal clinical parameters were recorded. A new automated technique was used to measure the thiol/disulphide homeostasis parameters, and ELISA was used to measure the amounts of VEGF in saliva.
Results: Children with or without diabetes had comparable clinical periodontal parameters and salivary VEGF levels (p>0.05). GI, PI, PD, and disulphide levels were significantly higher in the gingivitis subgroups than in the periodontally healthy subgroups (p<0.001). The gingivitis subgroups had significantly higher amounts of VEGF compared to the periodontally healthy subgroups (p<0.001).
Conclusions: Thiol/disulphide homeostasis shifts towards disulphide direction in diabetic children with gingivitis. Thiol/disulphide homeostasis and salivary VEGF levels may be diagnostic markers of gingival inflammation.

Keywords

saliva, gingivitis, diabetes mellitus, oxidative stress

References

• 1. Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ et al. Type 1 diabetes mellitus. Nat Rev Dis Primer. 2017;3(1):1-17.
• 2. Neyestani TR, Ghandchi Z, Eshraghian MR, Kalayi A, Shariatzadeh N, Houshiarrad A. Evidence for augmented oxidative stress in the subjects with type 1 diabetes and their siblings: A possible preventive role for antioxidants. Eur J Clin Nutr. 2012;66(9):1054-58.
• 3. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47(18):326-32.
• 4. Kırzıoğlu FY, Demirci S, Varol Ç, Ünlü MD, Calapoğlu M, Orhan H. Periodontal Health and Salivary Thiol-Disulphide Homeostasis in Multiple Sclerosis Patients. Med J SDU 2024;31(2):125-34.
• 5. Mengen E, Uçaktürk SA, Kocaay P, Kaymaz O, Neşelioğlu S, Erel O. The significance of thiol/disulfide homeostasis and ischemia-modified albumin levels in assessing oxidative stress in obese children and adolescents. J Clin Res Pediatr Endocrinol. 2020;12(1):45-54.
• 6. Ünal K, Erzin G, Yüksel RN, Alisik M, Erel O. Thiol/disulphide homeostasis in schizophrenia patients with positive symptoms. Nord J Psychiatry. 2018;72(4):281-84.
• 7. Arslan B, Arslan GA, Tuncer A, Karabudak R, Dinçel AS. Evaluation of thiol homeostasis in multiple sclerosis and neuromyelitis optica spectrum disorders. Front Neurol. 2021;12:716195.
• 8. Durmuş SY, Sahin NM, Ergin M, Neselioğlu S, Aycan Z, Erel Ö. How does thiol/disulfide homeostasis change in children with type 1 diabetes mellitus?. Diabetes Res Clin Pract. 2019;149:64-8.
• 9. Kulkarni VK, Dixit M, Balasubramanian S, Jetpurwala A. Gingival and periodontal diseases in children. Illustrated pediatric dentistry-part 2023;2:264.
• 10. Blufstein A, Pejcic N, Spettel K, Hausmann B, Seki D, Ertekin T, et al. Salivary microbiome and MRP‐8/14 levels in children with gingivitis, healthy children, and their mothers. J Periodontol 2024; 1:13 https://doi.org/10.1002/JPER.23-0632
• 11. Buranasin P, Kominato H, Mizutani K, Mikami R, Saito N, Takeda K, et al. Influence of reactive oxygen species on wound healing and tissue regeneration in periodontal and peri-implant tissues in diabetic patients. Antioxidants 2023;12(9):1787.
• 12. Gunasekaran S, Silva M, O’Connell MA, Manton DJ, Hallett KB. Caries experience and gingival health in children and adolescents with type 1 diabetes mellitus—A cross-sectional study. Pediatr Diabetes 2022;23(4):499-506.
• 13. Selway CA, Jensen ED, Pena AS, Smart G, Weyrich LS. Type 1 diabetes, periodontal health, and a familial history of hyperlipidaemia is associated with oral microbiota in children: a cross-sectional study. BMC Oral Health 2023;23(1):15.
• 14. Chiarelli F, Spagnoli A, Basciani FA, Tumini S, Mezzetti A, Cipollone F, et al. Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with type 1 diabetes mellitus: relation to glycaemic control and microvascular complications. Diabetic Medicine. 2000;17(9):650-56.
• 15. Sakallıoğlu EE, Aliyev E, Lütfioğlu M, Yavuz Ü, Açıkgöz G. Vascular endothelial growth factor (VEGF) levels of gingiva and gingival crevicular fluid in diabetic and systemically healthy periodontitis patients. Clin Oral Investig. 2007;115:120.
• 16. Afacan B, Öztürk VÖ, Paşalı Ç, Bozkurt E, Köse T, Emingil, G. Gingival crevicular fluid and salivary HIF‐1α, VEGF, and TNF‐α levels in periodontal health and disease. J Periodontol. 2019;90(7):788-97.
• 17. Varvařovská J, Racek J, Štětina R, Sýkora J, Pomahačová R, Rušavý Z, et al. Aspects of oxidative stress in children with type 1 diabetes mellitus. Biomed Pharmacother. 2004;58(10): 539-45.
• 18. American Diabetes Association; 13. Children and Adolescents: Standards of Medical Care in Diabetes—2019. Diabetes Care, 42: S148–S164.
• 19. Keles S, Anik A, Cevik O, Abas BI, Anik A. Gingival crevicular fluid levels of interleukin-18 and tumor necrosis factor-alpha in type 1 diabetic children with gingivitis. Clin Oral Investig. 2020; 24(10):3623-31.
• 20. Doğusal G, Afacan B, Bozkurt E, Sönmez I. Gingival crevicular fluid and salivary resistin and tumor necrosis factor‐alpha levels in obese children with gingivitis. J Periodontol. 2018;89(8):973-82.
• 21. Ates I, Kaplan M, Inan B, Alısık M, Erel O, Yilmaz N, et al. How does thiol/disulfide homeostasis change in prediabetic patients? Diabetes Res Clin Pract. 2015;110(2):166-71.
• 22. Ates I, Kaplan M, Yuksel M, Mese D, Alisik M, Erel Ö, et al. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation Endocr. 2016;51(1):47-51.
• 23. Preshaw PM, Alba AL, Herrera D, Jepsen S, Konstantinidis A, Makrilakis K, et al. Periodontitis and diabetes: a two-way relationship. Diabetologia 2012;55(1):21-31.
• 24. Leenders F, Groen N, de Graaf N, Engelse MA, Rabelink TJ, de Koning EJP, et al. Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity . Front Immunol. 2021;12:690379.
• 25. Liu X, Xu J, Li S, Wang X, Liu J, Li X. The prevalence of gingivitis and related risk factors in schoolchildren aged 6–12 years old. BMC Oral Health 2022;22(1):623.
• 26. Babatzia A, Papaioannou W, Stavropoulou A, Pandis N, Kanaka-Gantenbein C, Papagiannoulis L, et al. Clinical and microbial oral health status in children and adolescents with type 1 diabetes mellitus†. Int Dent J. 2020;70(2):136-44.
• 27. Ferizi L, Bimbashi V, Kelmendi J. Association between metabolic control and oral health in children with type 1 diabetes mellitus. BMC Oral Health. 2022;22(1):502.
• 28. Ismail AF, McGrath CP, Yiu CKY. Oral health status of children with type 1 diabetes: a comparative study. J Pediatr Endocrinol Metab. 2017; 30(11):1155-59.
• 29. Costa R, Ríos-Carrasco B, Monteiro L, López-Jarana P, Carneiro F, Relvas M. Association between Type 1 Diabetes Mellitus and Periodontal Diseases. J Clin Med. 2023;12(3):1147.
• 30. Santamaria-Jr M, Bagne L, Zaniboni E, Santamaria MP, Jardini MAN, Felonato M, et al. Diabetes mellitus and periodontitis: Inflammatory response in orthodontic tooth movement. Orthod Craniofac Res. 2020;23(1):27-34.
• 31. Prapulla DV, Sujatha PB, Pradeep AR (2007) Gingival Crevicular Fluid VEGF Levels in Periodontal Health and Disease. J Periodontol. 2007;78(9):1783-7.
• 32. Patil PB, Patil BR. Saliva: A diagnostic biomarker of periodontal diseases. J Indian Soc Periodontol. 2011;15(4):310-7.
• 33. Belstrøm D, Damgaard C, Könönen E, Gürsoy M, Holmstrup P, Gürsoy UK. Salivary cytokine levels in early gingival inflammation J Oral Microbiol. 2017; 9(1):1364101.
• 34. Pradeep AR, Prapulla DV, Sharma A, Sujatha PB. Gingival crevicular fluid and serum vascular endothelial growth factor: Their relationship in periodontal health, disease and after treatment. Cytokine. 2011;54(2):200-4.
• 35. Seckin D, Ilhan N, Ilhan N, Ertugrul S. Glycaemic control, markers of endothelial cell activation and oxidative stress in children with type 1 diabetes mellitus. Diabetes Res Clin Pract.2006;73(2):191-7.
• 36. Padma R, Sreedhara A, Indeever P, Sarkar I, Kumar CS (2014). Vascular Endothelial Growth Factor Levels in Gingival Crevicular Fluid Before and after Periodontal Therapy. J Clin Diagn Res J. 2014; 8(11):ZC75-9.
• 37. Hertiš Petek T, Petek T, Močnik M, Marčun Varda N. Systemic Inflammation, Oxidative Stress and Cardiovascular Health in Children and Adolescents: A Systematic Review. Antioxidants. 2022; 11(5):894.
• 38. Hasan HR, Abdel Rasul RJ. Impact of psoriasis disease and its treatment with Etanercept on serum and saliva thiol-disulfide homeostasis. Egypt J Chem. 2023;66(9):37-46.
• 39. Tvarijonaviciute A, Martinez-Lozano N, Rios R, Marcilla de Teruel MC, Garaulet M, Cerón JJ. Saliva as a non-invasive tool for assessment of metabolic and inflammatory biomarkers in children. Clin Nutr. 2020;39(8):2471-8.
• 40. Tayman MA, Bal C, Nural C, Günhan M (2021) Evaluation of Dynamic Thiol/Disulphide Homeostasis in Patients with Periodontitis. Meandros Med Dental J. 2021;22:41-9.
• 41. Kallinikou D, Soldatou A, Tsentidis C, Louraki M, Kanaka‐Gantenbein C, Kanavakis, E et al. Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: diagnosis, pathogenesis, and associated genetic markers. Diabetes Metab Res Rev. 2019;35(7), e3178.
• 42. Rossino MG, Lulli M, Amato R, Cammalleri M, Dal Monte M, Casini G. Oxidative stress induces a VEGF autocrine loop in the retina: relevance for diabetic retinopathy. Cells 2020; 9(6):1452
• 43. Domingueti, CP, Dusse LMSA, das Graças Carvalho M, de Sousa LP, Gomes KB, Fernandes AP. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complications. 2016;30(4):738-45.