Periodontal Diseases in Patients with Type 1 Diabetes Mellitus: Pathogenetic and Clinical Aspects

INTRODUCTION: Periodontal diseases in patients with type 1 diabetes mellitus (T1DM) represent a multifactorial clinicopathogenetic problem, driven by disturbances in carbohydrate metabolism, immune response, and microcirculation. Despite advances in modern medicine, timely diagnosis and optimization of therapy for periodontal diseases in T1DM remain of high clinical and scientific significance.

OBJECTIVE: To systematize current data on pathogenetic and clinical aspects underlying the bidirectional relationship between T1DM and periodontal diseases.

MATERIALS AND METHODS: We analyzed scientific publications from the past 20 years in PubMed, Scopus, and Google Scholar using key terms: “type 1 diabetes mellitus”, “periodontal diseases in type 1 diabetes”, “periodontitis”, and “bidirectional relationship”.

KEY FINDINGS: Current evidence confirms the presence of a bidirectional relationship between T1DM and periodontal diseases. Chronic hyperglycemia contributes to the development and progression of periodontitis through alterations in the oral microbiome, activation of the AGEs–RAGE signaling pathway, microvascular dysfunction, neutrophil impairment, and defective reparative processes. Conversely, chronic periodontal inflammation exacerbates systemic inflammation and is associated with worsened glycemic control. These findings highlight the multifactorial pathogenesis of periodontal diseases in T1DM and underscore the need for an interdisciplinary approach and early diagnosis.

CONCLUSION: Improvement of early diagnostic methods and implementation of interdisciplinary, personalized management strategies for patients with T1DM and periodontal diseases may enhance clinical outcomes. A promising direction is the development and validation of integrated clinical–laboratory algorithms for risk assessment and prognosis of dental complications in T1DM.

1. Dedov II, Shestakova MV, Vikulova OK, et al. Epidemiology and key clinical and therapeutic indicators of diabetes mellitus in Russian Federation according to the World Health Organization’s strategy goals. Diabetes mellitus. 2025;28(1):4–17. (In Russ.)] doi: https://doi.org/10.14341/DM13292

2. 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

3. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2021. Results. Seattle: Institute for Health Metrics and Evaluation (IHME); 2022. Available from: https://www.healthdata.org/research-analysis/gbd

4. International Diabetes Federation. IDF Diabetes Atlas, 11th edn. Brussels: International Diabetes Federation; 2025. Available from: https://diabetesatlas.org/resources/idf-diabetes-atlas-2025/

5. Redondo MJ, Fain PR, Eisenbarth GS. Genetics of type 1A diabetes. Recent Prog Horm Res. 2001;56:69–89. doi: https://doi.org/10.1210/rp.56.1.69

6. Atkinson MA. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2(11):a007641. doi: https://doi.org/10.1101/cshperspect.a007641

7. Antvorskov JC, Josefsen K, Engkilde K, et al. Dietary gluten and the development of type 1 diabetes. Diabetologia. 2014;57(9):1770–1780. doi: https://doi.org/10.1007/s00125-014-3265-1

8. Yanushevich OO, Dmitrieva LA, Ajvazova RA, et al. Parodontologija. Ed by Yanushevich O.O., Dmitrieva L.A. Moscow: GEOTAR-Media; 2018. (In Russ.)]

9. Raza M. Abud DG, Wang J, et al. Ease and practicability of the 2017 classification of periodontal diseases and conditions: a study of dental electronic health records. BMC Oral Health. 2024;24(621). doi: https://doi.org/10.1186/s12903-024-04385-5

10. Manouchehr-Pour M, Bissada NF. Periodontal disease in juvenile and adult diabetic patients: a review of the literature. J Am Dent Assoc. 1983;107(5):766–770. doi: https://doi.org/10.14219/jada.archive.1983.0346

11. Löe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16(1):329–334.

12. Rodrigues Oliveira SM, Rebocho A, Ahmadpour E, et al. Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices. Micromachines (Basel). 2023;14(1):151. doi: https://doi.org/10.3390/mi14010151

13. Ikegami H. Which comes first in type 1 diabetes: Autoimmunity or dysglycemia? J Diabetes Investig. 2023;14(5):645–647. doi: https://doi.org/10.1111/jdi.13984

14. D’Aiuto F, Gkranias N, Bhowruth D, et al. Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial. Lancet Diabetes Endocrinol. 2018;6(12):954–965. doi: https://doi.org/10.1016/S2213-8587(18)30038-X

15. Folli F, Corradi D, Fanti P, et al. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus microand macrovascular complications: avenues for a mechanisticbased therapeutic approach. Curr Diabetes Rev. 2011;7(5):313–324. doi: https://doi.org/10.2174/157339911797415585

16. Popławska-Kita A, Siewko K, Szpak P, et al. Association between type 1 diabetes and periodontal health. Adv Med Sci. 2014;59(1):126–131. doi: https://doi.org/10.1016/j.advms.2014.01.002

17. Graves DT, Ding Z, Yang Y. The impact of diabetes on periodontal diseases. Periodontol 2000. 2020;82(1):214–224. doi: https://doi.org/10.1111/prd.12318

18. Adam HS, Molinsky R, Bohn B, et al. Clinical attachment loss is cross-sectionally associated with elevated glucose among adults without diabetes. J Clin Periodontol. 2024;51(5):522–535. doi: https://doi.org/10.1111/jcpe.13945

19. Jindal A, Parihar AS, Sood M, Singh P, Singh N. Relationship between Severity of Periodontal Disease and Control of Diabetes (Glycated Hemoglobin) in Patients with Type 1 Diabetes Mellitus. J Int Oral Health. 2015;7(Suppl 2):17–20.

20. Cugini C, Ramasubbu N, Tsiagbe VK, Fine DH. Dysbiosis From a Microbial and Host Perspective Relative to Oral Health and Disease. Front Microbiol. 2021;12:617485. doi https://doi.org/:10.3389/fmicb.2021.617485

21. Sabharwal A, Gomes-Filho IS, Stellrecht E, Scannapieco FA. Role of periodontal therapy in management of common complex systemic diseases and conditions: An update. Periodontol 2000. 2018;78(1):212–226. doi: https://doi.org/10.1111/prd.12226

22. Carelli M, Maguolo A, Zusi C, et al. Oral Microbiota in Children and Adolescents with Type 1 Diabetes Mellitus: Novel Insights into the Pathogenesis of Dental and Periodontal Disease. Microorganisms. 2023;11(3):668. doi: https://doi.org/10.3390/microorganisms11030668

23. Meyle J, Chapple I. Molecular aspects of the pathogenesis of periodontitis. Periodontol 2000. 2015;69(1):7–17. doi: https://doi.org/10.1111/prd.12104

24. Qin H, Li G, Xu X, et al. The role of oral microbiome in periodontitis under diabetes mellitus. J Oral Microbiol. 2022;14(1):2078031. doi: https://doi.org/10.1080/20002297.2022.2078031

25. Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Clin Periodontol. 2013;40 Suppl 14:S113-S134. doi: https://doi.org/10.1111/jcpe.12059

26. Yoon MS, Jankowski V, Montag S, et al. Characterisation of advanced glycation endproducts in saliva from patients with diabetes mellitus. Biochem Biophys Res Commun. 2004;323(2):377–381. doi: https://doi.org/10.1016/j.bbrc.2004.08.118

27. Graves D.T., et al. Diabetes-associated mechanisms in periodontal disease. Periodontology 2000. 2020;82(1):84–93.

28. Yan SF, Ramasamy R, Schmidt AM. Receptor for AGE (RAGE) and its ligands-cast into leading roles in diabetes and the inflammatory response. J Mol Med (Berl). 2009;87(3):235–247. doi: https://doi.org/10.1007/s00109-009-0439-2

29. Lalla E, Lamster IB, Feit M, et al. Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. J Clin Invest. 2000;105(8):1117–1124. doi: https://doi.org/10.1172/JCI8942

30. Goova MT, Li J, Kislinger T, et al. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol. 2001;159(2):513–525. doi: https://doi.org/10.1016/S0002-9440(10)61723-3

31. Kashket S, Maiden MF, Haffajee AD, Kashket ER. Accumulation of methylglyoxal in the gingival crevicular fluid of chronic periodontitis patients. J Clin Periodontol. 2003;30(4):364–367. doi: https://doi.org/10.1034/j.1600-051x.2003.00322.x

32. Schmidt AM, Weidman E, Lalla E, et al. Advanced glycation endproducts (AGEs) induce oxidant stress in the gingiva: a potential mechanism underlying accelerated periodontal disease associated with diabetes. J Periodontal Res. 1996;31(7):508–515. doi: https://doi.org/10.1111/j.1600-0765.1996.tb01417.x

33. Takeda M, Ojima M, Yoshioka H, et al. Relationship of serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients. J Periodontol. 2006;77(1):15–20. doi: https://doi.org/10.1902/jop.2006.77.1.15

34. Scardina GA, Cacioppo A, Messina P. Periodontal microcirculation in diabetics: an in vivo non-invasive analysis by means of videocapillaroscopy. Med Sci Monit. 2012;18(2):CR58-CR64. doi: https://doi.org/10.12659/msm.882456

35. Ilea A, Băbţan AM, Boşca BA, et al. Advanced glycation end products (AGEs) in oral pathology. Arch Oral Biol. 2018;93:22–30. doi: https://doi.org/10.1016/j.archoralbio.2018.05.013

36. Balci Yuce H, Karatas Ö, Tulu F, Altan A, Gevrek F. Effect of diabetes on collagen metabolism and hypoxia in human gingival tissue: a stereological, histopathological, and immunohistochemical study. Biotech Histochem. 2019;94(1):65–73. doi: https://doi.org/10.1080/10520295.2018.1508745

37. Polak D, Shapira L. An update on the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Clin Periodontol. 2018;45(2):150–166. doi: https://doi.org/10.1111/jcpe.12803

38. Mi Z, Liu H, Zhang F. Advances in the Immunology and Genetics of Leprosy. Front Immunol. 2020;11:567. Published 2020 Apr 16. doi: https://doi.org/10.3389/fimmu.2020.00567

39. Preshaw PM, Alba AL, Herrera D, et al. Periodontitis and diabetes: a two-way relationship. Diabetologia. 2012;55(1):21–31. doi: https://doi.org/10.1007/s00125-011-2342-y