Diabetes and Periodontitis: Common Mechanisms and Clinical Implications

Abstract

The aim of this review is to evaluate the bidirectional relationship between diabetes and periodontitis based on current literature and to examine how these two chronic diseases influence each other in terms of biological mechanisms and clinical outcomes. National and international studies were reviewed. Clinical and experimental research investigating the relationship between diabetes and periodontitis were analyzed. The studies were classified and evaluated according to the effects of diabetes on periodontal tissues, the impact of periodontitis on glycemic control, and the underlying biological mechanisms linking the two conditions. The findings indicate that diabetes is a significant risk factor in the development of periodontal diseases. Hyperglycemia promotes the accumulation of advanced glycation end products (AGEs) and enhances the inflammatory response, accelerating the destruction of periodontal tissues. Conversely, periodontitis increases systemic inflammation, thereby worsening insulin resistance and negatively affecting glycemic control. It has been reported that periodontal treatment can lead to a significant improvement in HbA1c levels among diabetic patients. A bidirectional relationship exists between diabetes and periodontitis. Therefore, periodontal health should be regularly assessed in diabetic individuals. Considering the positive effects of periodontal therapy on systemic health, a multidisciplinary approach should be adopted, and individualized follow-up plans should be developed for each patient.

Keywords

• Diabetes
• Periodontitis
• Periodontal therapy

Diyabet ve Periodontitis: Ortak Mekanizmalar ve Klinik Sonuçlar

Abstract

Bu derleme çalışmasının amacı, diyabet ve periodontitis arasındaki çift yönlü ilişkiyi mevcut literatür doğrultusunda değerlendirmek, bu iki kronik hastalığın birbirini nasıl etkilediğini biyolojik mekanizmalar ve klinik sonuçlar açısından incelemektir. Çalışmamızda ulusal ve uluslararası literatürler incelenmiştir. Diyabet ve periodontitis arasındaki ilişkiyi değerlendiren klinik ve deneysel çalışmalar gözden geçirilmiştir. İncelenen araştırmalar, diyabetin periodontal dokular üzerindeki etkileri, periodontitisin glisemik kontrol üzerine yansımaları ve bu etkileşimin biyolojik temelleri açısından sınıflandırılarak değerlendirilmiştir. Elde edilen veriler diyabetin periodontal hastalıkların gelişiminde önemli bir risk faktörü olduğunu göstermektedir. Hiperglisemi, ileri glikasyon son ürünlerinin (AGEs) birikimine ve inflamatuar yanıtın artmasına neden olarak periodontal dokularda destrüksiyonu hızlandırmaktadır. Periodontitisin ise sistemik inflamasyonu artırarak insülin direncini kötüleştirdiği ve glisemik kontrolü olumsuz etkilediği görülmüştür. Periodontal tedavinin diyabetli hastalarda HbA1c düzeylerinde anlamlı iyileşme sağladığı bildirilmiştir. Diyabet ve periodontitis arasında karşılıklı etkileşime dayalı çift yönlü bir ilişki bulunmaktadır. Bu nedenle, diyabetli bireylerde periodontal sağlık düzenli olarak değerlendirilmelidir. Periodontal tedavinin sistemik sağlık üzerindeki olumlu etkileri göz önünde bulundurularak multidisipliner bir yaklaşım benimsenmeli ve hastaların bireyselleştirilmiş izlem planları oluşturulmalıdır.

Keywords

• Diyabet
• Periodontitis
• Periodontal tedavi

References

1. Amir J, Waite M, Tobler J, Catalfamo DL, Koutouzis T, Katz J, et al. The role of hyperglycemia in mechanisms of exacerbated inflammatory responses within the oral cavity. Cell Immunol. 2011;272(1):45-52.
2. Bharateesh J, Ahmed M, Kokila G. Diabetes and oral health: a case-control study. Int J Prev Med. 2012;3(11):806-9.
3. Cao R, Li Q, Wu Q, Yao M, Chen Y, Zhou H. Effect of non-surgical periodontal therapy on glycemic control of type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis. BMC Oral Health. 2019;19(1):176.
4. Claudino M, Gennaro G, Cestari TM, Spadella CT, Garlet GP, Assis GF. Spontaneous periodontitis development in diabetic rats involves an unrestricted expression of inflammatory cytokines and tissue destructive factors in the absence of major changes in commensal oral microbiota. Exp Diabetes Res. 2012;2012:356841.
5. Daniel R, Gokulanathan S, Shanmugasundaram N, Lakshmigandhan M, Kavin T. Diabetes and periodontal disease. J Pharm Bioallied Sci. 2012;4(Suppl 2):S280-2.
6. Darré L, Vergnes J-N, Gourdy P, Sixou M. Efficacy of periodontal treatment on glycaemic control in diabetic patients: a meta-analysis of interventional studies. Diabetes Metab. 2008;34(5):497-506.
7. Demmer RT, Holtfreter B, Desvarieux M, Jacobs DR, Jr., Kerner W, Nauck M, et al. The influence of type 1 and type 2 diabetes on periodontal disease progression: prospective results from the Study of Health in Pomerania (SHIP). Diabetes Care. 2012;35(10):2036-42.
8. Di Domenico GL, Minoli M, Discepoli N, Ambrosi A, de Sanctis M. Effectiveness of periodontal treatment to improve glycemic control: an umbrella review. Acta Diabetologica. 2023;60(1):101-13.

9. Ding Q, Keller JN. Splice variants of the receptor for advanced glycosylation end products (RAGE) in human brain. Neurosci Lett. 2004;373(1):67-72.
10. Desta T, Li J, Chino T, Graves D. Altered fibroblast proliferation and apoptosis in diabetic gingival wounds. J Dent Res. 2010;89(6):609-14.
11. Genco RJ, Borgnakke WS. Diabetes as a potential risk for periodontitis: association studies. Periodontol 2000. 2020;83(1):40-5.
12. Graves DT, Ding Z, Yang Y. The impact of diabetes on periodontal diseases. Periodontol 2000. 2020;82(1):214-24.
13. Grover HS, Luthra S. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease. J Indian Soc Periodontol. 2013;17(3):292-301.
14. Harigaya H, Chiba-Ohkuma R, Karakida T, Yamamoto R, Fujii-Abe K, Kawahara H, et al. Potential for drug repositioning of midazolam as an inhibitor of inflammatory bone resorption. Int J Mol Sci. 2024;25(14).
15. Hales CN, Barker DJ. The thrifty phenotype hypothesis: Type 2 diabetes. Br Med Bull. 2001;60(1):5-20.
16. Hujoel PP, Stott-Miller M. Retinal and gingival hemorrhaging and chronic hyperglycemia. Diabetes Care. 2011;34(1):181-3.
17. Iacopino AM, Cutler CW. Pathophysiological relationships between periodontitis and systemic disease: recent concepts involving serum lipids. J Periodontol. 2000;71(8):1375-84.
18. Janket S-J, Wightman A, Baird A, Van Dyke T, Jones J. Does periodontal treatment improve glycemic control in diabetic patients? A meta-analysis of intervention studies. J Dent Res. 2005;84(12):1154-9.
19. Kara G, Cifcibasi E, Karsidag K, Cintan S. Short term effects of periodontal therapy on inflammatory markers in patients with type-2 diabetes. Saudi Med J. 2015;36(4):469.
20. Khan M, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107-11.
21. Ko KI, Sculean A, Graves DT. Diabetic wound healing in soft and hard oral tissues. Transl Res. 2021;236:72-86.
22. Lalla E, Cheng B, Lal S, Kaplan S, Softness B, Greenberg E, et al. Diabetes mellitus promotes periodontal destruction in children. J Clin Periodontol. 2007;34(4):294-8.
23. Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S. Adipokines: molecular links between obesity and atherosclerosis. Am J Physiol Heart Circ Physiol. 2005;288(5):H2031-H41.
24. Li Y, Du Z, Xie X, Zhang Y, Liu H, Zhou Z, et al. Epigenetic changes caused by diabetes and their potential role in the development of periodontitis. J Diabetes Investig. 2021;12(8):1326-35.
25. Liew AKC, Punnanithinont N, Lee YC, Yang J. Effect of non-surgical periodontal treatment on HbA1c: a meta-analysis of randomized controlled trials. Aust Dent J. 2013;58(3):350-7.
26. Liu J, Wang Y, Shi Q, Wang X, Zou P, Zheng M, et al. Mitochondrial DNA efflux maintained in gingival fibroblasts of patients with periodontitis through ROS/mPTP pathway. Oxid Med Cell Longev. 2022;2022:1000213.
27. McKenna SJ. Dental management of patients with diabetes. Dent Clin North Am. 2006;50(4):591-606.
28. Monnier VM, Glomb M, Elgawish A, Sell DR. The mechanism of collagen cross-linking in diabetes: a puzzle nearing resolution. Diabetes. 1996;45(Suppl 3):S67-S72.
29. Murillo J, Wang Y, Xu X, Klebe RJ, Chen Z, Zardeneta G, et al. Advanced glycation of type I collagen and fibronectin modifies periodontal cell behavior. J Periodontol. 2008;79(11):2190-9.
30. Nascimento GG, Leite FR, Vestergaard P, Scheutz F, Lopez R. Does diabetes increase the risk of periodontitis? A systematic review and meta-regression analysis of longitudinal prospective studies. Acta Diabetol. 2018;55(7):653-67.
31. Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci (Qassim). 2017;11(2):72-80.
32. Nguyen ATM, Akhter R, Garde S, Scott C, Twigg SM, Colagiuri S, et al. The association of periodontal disease with the complications of diabetes mellitus: a systematic review. Diabetes Res Clin Pract. 2020;165:108244.
33. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809-20.
34. Preshaw PM, Bissett SM. Periodontitis and diabetes. Br Dent J. 2019;227(7):577-84.
35. Rahbar S. The discovery of glycated hemoglobin: a major event in the study of nonenzymatic chemistry in biological systems. Ann N Y Acad Sci. 2005;1043(1):9-19.
36. Remijsen Q, Berghe TV, Wirawan E, Asselbergh B, Parthoens E, De Rycke R, et al. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res. 2011;21(2):290-304.
37. Rees TD. Periodontal management of the patient with diabetes mellitus. Periodontol 2000. 2000;23(1):131-47.
38. Schmidt AM, Hori O, Cao R, Yan SD, Brett J, Wautier J-L, et al. RAGE: a novel cellular receptor for advanced glycation end products. Diabetes. 1996;45(Suppl 3):S77-S80.
39. Siddiqi A, Zafar S, Sharma A, Quaranta A. Diabetes mellitus and periodontal disease: The call for interprofessional education and interprofessional collaborative care — A systematic review of the literature. J Interprof Care. 2022;36(1):93-101.
40. Simpson TC, Clarkson JE, Worthington HV, MacDonald L, Weldon JC, Needleman I, et al. Treatment of periodontitis for glycaemic control in people with diabetes mellitus. Cochrane Database Syst Rev. 2022;4:CD013253.
41. Simpson TC, Weldon JC, Worthington HV, Needleman I, Wild SH, Moles DR, et al. Treatment of periodontal disease for glycaemic control in people with diabetes mellitus. Cochrane Database Syst Rev. 2015;11:CD004714.
42. Southerland JH, Taylor GW, Offenbacher S. Diabetes and Periodontal Infection: Making the Connection. Clin Diabetes. 2005;23(4):171-8.
43. Stöhr J, Barbaresko J, Neuenschwander M, Schlesinger S. Bidirectional association between periodontal disease and diabetes mellitus: a systematic review and meta-analysis of cohort studies. Sci Rep. 2021;11(1):13686.
44. Sanz M, Ceriello A, Buysschaert M, Chapple I, Demmer RT, Graziani F, et al. Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. Diabetes Res Clin Pract. 2018;137:231-41.
45. Turner C. Diabetes mellitus and periodontal disease: the profession’s choices. Br Dent J. 2022;233(7):537-8.
46. Vergnes J-N. Review finds periodontal treatment has short term benefits for diabetics. Evid Based Dent. 2015;16(3):78-9.
47. Wang X, Han X, Guo X, Luo X, Wang D. The effect of periodontal treatment on hemoglobin a1c levels of diabetic patients: a systematic review and meta-analysis. PLoS One. 2014;9(9):e108412.
48. Xiang D-d, Sun Y-x, Jiao C, Guo Y-q, Fei Y-x, Ren B-q, et al. Diabetes and periodontitis: the role of a high-glucose microenvironment in periodontal tissue cells and corresponding therapeutic strategies. Stem Cell Res Ther. 2025;16(1):366.
49. Yao D, Brownlee M. Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes. 2010;59(1):249-55.