Int J Stomatol

Int J Stomatol ›› 2025, Vol. 52 ›› Issue (2): 231-237.doi: 10.7518/gjkq.2025009

• Reviews • Previous Articles     Next Articles

Progress in research on the correlation of inflammatory pulpal and periapical disease to diabetes mellitus and rela-ted mechanisms

Xinlu Dong(),Laijun Xu,Jianying Zhang,Minmin Chen()   

  1. Xiangya School of Stomatology, Central South University & Dept. of Endodontics, Hunan Xiangya Stomatological Hospital & Hunan Key Laboratory of Oral Health Research & Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Changsha 410008, China
  • Received:2024-04-28 Revised:2024-09-10 Online:2025-03-01 Published:2025-03-01
  • Contact: Minmin Chen E-mail:226812031@csu.edu.cn;chenminmin@csu.edu.cn
  • Supported by:
    Natural Science Foundation of Hunan Province(2022JJ40733);Scientific Research Program of Hunan Provincial Health Commission(202208015033);Natural Science Foundation of Changsha(kq2208180)

RichHTML

31

PDF (PC)

167

Abstract:

Dental pulp and periapical diseases are prevalent infectious oral conditions that can affect the well-being of the stomatognathic system. In recent years, a growing number of studies have highlighted the correlations of pulp and periapical diseases to diabetes, but the mechanism underlying this correlation remains unclear. This review aims to present a comprehensive summary of the possible mechanisms, including insulin resistance, microbial immune inflammatory response, imbalance between osteogenesis and osteolysis, and oxidative stress. Ultimately, this review seeks to offer a theoretical framework and clinical guidance for the management of dental pulp and periapical diseases in individuals with diabetes mellitus.

Key words: dental pulp disease, periapical disease, diabetes mellitus, microorganism, immunity

CLC Number: 

  • R781.3

TrendMD: 

"

1 Duncan HF, Kirkevang LL, Peters OA, et al. Treatment of pulpal and apical disease: the European Society of Endodontology (ESE) S3-level clinical practice guideline[J]. Int Endod J, 2023, 56(): 238-295.
2 Segura-Egea JJ, Cabanillas-Balsera D, Martín-Gon-zález J, et al. Impact of systemic health on treatment outcomes in endodontics[J]. Int Endod J, 2023, 56(): 219-235.
3 Lalla E, Papapanou PN. Diabetes mellitus and perio-dontitis: a tale of two common interrelated diseases[J]. Nat Rev Endocrinol, 2011, 7(12): 738-748.
4 Bendek MJ, Canedo-Marroquín G, Realini O, et al. Periodontitis and gestational diabetes mellitus: a potential inflammatory vicious cycle[J]. Int J Mol Sci, 2021, 22(21): 11831.
5 Gaeta C, Marruganti C, Ali IAA, et al. The presence of Enterococcus faecalis in saliva as a risk factor for endodontic infection[J]. Front Cell Infect Microbiol, 2023, 13: 1061645.
6 Siqueira JF Jr, Rôças IN. A critical analysis of research methods and experimental models to study the root canal microbiome[J]. Int Endod J, 2022, 55(): 46-71.
7 Limeira FIR, Arantes DC, de Souza Oliveira C, et al. Root canal treatment and apical periodontitis in a Brazilian population with type 1 diabetes mellitus: a cross-sectional paired study[J]. J Endod, 2020, 46(6): 756-762.
8 Srivastava KC, Shrivastava D, Nagarajappa AK, et al. Assessing the prevalence and association of pulp stones with cardiovascular diseases and diabetes mellitus in the Saudi Arabian population-a CBCT based study[J]. Int J Environ Res Public Health, 2020, 17(24): 9293.
9 Gonzalez Marrero Y, Kobayashi Y, Ihsan MS, et al. Altered prevalence of pulp diagnoses in diabetes mellitus patients: a retrospective study[J]. J Endod, 2022, 48(2): 208-212.e3.
10 Loureiro C, Buzalaf MAR, Pessan JP, et al. Proteomic analysis of infected root canals with apical periodontitis in patients with type 2 diabetes mellitus: a cross-sectional study[J]. Int Endod J, 2022, 55(9): 910-922.
11 Astolphi RD, Curbete MM, Chiba FY, et al. Periapical lesions decrease insulin signaling in rat skeletal muscle[J]. J Endod, 2015, 41(8): 1305-1310.
12 Pereira RF, de Oliveira da Mota MS, de Lima Coutinho Mattera MS, et al. Periapical lesions decrease Akt serine phosphorylation and plasma membrane GLUT4 content in rat skeletal muscle[J]. Clin Oral Investig, 2016, 20(7): 1625-1630.
13 Cintra LT, da Silva Facundo AC, Prieto AK, et al. Blood profile and histology in oral infections asso-ciated with diabetes[J]. J Endod, 2014, 40(8): 1139-1144.
14 Prieto AKC, Gomes-Filho JE, Azuma MM, et al. Influence of apical periodontitis on stress oxidative parameters in diabetic rats[J]. J Endod, 2017, 43(10): 1651-1656.
15 Chien WC, Fu E, Chung CH, et al. Type 2 diabetes mellitus and periodontitis: bidirectional association in population-based 15-year retrospective cohorts[J]. J Clin Endocrinol Metab, 2023, 108(11): e1289-e1297.
16 Shi NX, Kong CF, Yuan L, et al. The bidirectional relationship between periodontitis and diabetes: new prospects for stem cell-derived exosomes[J]. Biomed Pharmacother, 2023, 165: 115219.
17 Zhao M, Xie Y, Gao W, et al. Diabetes mellitus promotes susceptibility to periodontitis-novel insight into the molecular mechanisms[J]. Front Endocrinol (Lausanne), 2023, 14: 1192625.
18 Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and fun-ction in health and disease[J]. J Cell Physiol, 2018, 233(9): 6425-6440.
19 Ying W, Fu WX, Lee YS, et al. The role of macrophages in obesity-associated islet inflammation and β‑cell abnormalities[J]. Nat Rev Endocrinol, 2020, 16(2): 81-90.
20 Blasco-Baque V, Garidou L, Pomié C, et al. Perio-dontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response[J]. Gut, 2017, 66(5): 872-885.
21 Gomes JMG, Costa JA, Alfenas RCG. Metabolic endotoxemia and diabetes mellitus: a systematic review[J]. Metabolism, 2017, 68: 133-144.
22 Ballato E, Deepika F, Prado M, et al. Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus[J]. Front Endocrinol, 2022, 13: 936159.
23 An YN, Zhang HF, Wang C, et al. Activation of ROS/MAPKs/NF-κB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis[J]. FASEB J, 2019, 33(11): 12515-12527.
24 Liu LS, Zhang C, Hu YJ, et al. Protective effect of metformin on periapical lesions in rats by decrea-sing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin[J]. J Endod, 2012, 38(7): 943-947.
25 Uzunoglu-Ozyurek E, Önal G, Dökmeci S. Odonto/osteogenic differentiation of dental pulp stem cells of type 1 diabetic patients with mineral trioxide ag-gregate/1α, 25-dihydroxyvitamin D3 combination[J]. J Endod, 2022, 48(4): 516-526.
26 Alsamahi S, Milne TM, Hussaini H, et al. Type 2 diabetes and the clinically normal pulp: an in vitro study[J]. Int Endod J, 2022, 55(6): 660-671.
27 Al-Anesi MA, Abu-Seida AM, El Ashry SH, et al. Influence of insulin on the healing of exposed dental pulp after pulp capping: an experimental study in a dog model[J]. Spec Care Dentist, 2021, 41(1): 49-59.
28 Azuma MM, Gomes-Filho JE, Prieto AKC, et al. Diabetes increases interleukin-17 levels in periapical, hepatic, and renal tissues in rats[J]. Arch Oral Biol, 2017, 83: 230-235.
29 Borgo Sarmento E, Helena Teixeira de Lima Ribeiro Andrade R, Cristina Gomes C, et al. Proinflammatory cytokine expression in apical periodontitis from diabetic patients[J]. Int J Dent, 2023, 2023: 4961827.
30 Samuel RO, Ervolino E, de Azevedo Queiroz ÍO, et al. Th1/Th2/Th17/treg balance in apical periodontitis of normoglycemic and diabetic rats[J]. J Endod, 2019, 45(8): 1009-1015.
31 Garlet GP, Cardoso CR, Campanelli AP, et al. The essential role of IFN-γin the control of lethal Aggregatibacter actinomycetemcomitans infection in mice[J]. Microbes Infect, 2008, 10(5): 489-496.
32 De la Torre-Luna R, Domínguez-Pérez RA, Guillén-Nepita AL, et al. Prevalence of Candida albicans in primary endodontic infections associated with a higher frequency of apical periodontitis in type two diabetes mellitus patients[J]. Eur J Clin Microbiol Infect Dis, 2020, 39(1): 131-138.
33 Soza-Bolaños AI, Domínguez-Pérez RA, Ayala-Herrera JL, et al. Presence of methanogenic archaea in necrotic root canals of patients with or without type 2 diabetes mellitus[J]. Aust Endod J, 2023, 49(3): 641-647.
34 Vázquez-Ramos VR, Pérez-Serrano RM, García-Solís P, et al. Root canal microbiota as an augmen-ted reservoir of antimicrobial resistance genes in type 2 diabetes mellitus patients[J]. J Appl Oral Sci, 2023, 30: e20220362.
35 Kimball JS, Johnson JP, Carlson DA. Oxidative stress and osteoporosis[J]. J Bone Joint Surg Am, 2021, 103(15): 1451-1461.
36 Jaganjac M, Milkovic L, Zarkovic N, et al. Oxidative stress and regeneration[J]. Free Radic Biol Med, 2022, 181: 154-165.
37 Lee YH, Kim GE, Song YB, et al. Davallialactone reduces inflammation and repairs dentinogenesis on glucose oxidase-induced stress in dental pulp cells[J]. J Endod, 2013, 39(11): 1401-1406.
38 Milosavljević A, DJukić L, Toljić B, et al. Melatonin levels in human diabetic dental pulp tissue and its effects on dental pulp cells under hyperglycaemic conditions[J]. Int Endod J, 2018, 51(10): 1149-1158.
39 Jiao Y, Ma S, Wang YR, et al. N-acetyl cysteine depletes reactive oxygen species and prevents dental monomer-induced intrinsic mitochondrial apoptosis in vitro in human dental pulp cells[J]. PLoS One, 2016, 11(1): e0147858.
40 Wu DN, Yan LY, Zheng CC, et al. Akt-GSK3β‑ mPTP pathway regulates the mitochondrial dysfunction contributing to odontoblasts apoptosis induced by glucose oxidative stress[J]. Cell Death Discov, 2022, 8: 168.
41 Takanche JS, Lee YH, Kim JS, et al. Anti-inflammatory and antioxidant properties of Schisandrin C promote mitochondrial biogenesis in human dental pulp cells[J]. Int Endod J, 2018, 51(4): 438-447.
42 Nagendrababu V, Segura-Egea JJ, Fouad AF, et al. Association between diabetes and the outcome of root canal treatment in adults: an umbrella review[J]. Int Endod J, 2020, 53(4): 455-466.
43 Cabanillas-Balsera D, Martín-González J, Montero-Miralles P, et al. Association between diabetes and nonretention of root filled teeth: a systematic review and meta-analysis[J]. Int Endod J, 2019, 52(3): 297-306.
44 Paljević E, Brekalo Pršo I, Vidas Hrstić J, et al. Healing of apical periodontitis in type Ⅱ diabetes mellitus patients: a prospective study[J]. Oral Dis, 2024, 30(5): 3422-3430.
45 Gupta A, Aggarwal V, Mehta N, et al. Diabetes mellitus and the healing of periapical lesions in root filled teeth: a systematic review and meta-analysis[J]. Int Endod J, 2020, 53(11): 1472-1484.
46 Liu XY, He GY, Qiu ZJ, et al. Diabetes mellitus increases the risk of apical periodontitis in endodontically-treated teeth: a meta-analysis from 15 studies[J]. J Endod, 2023, 49(12): 1605-1616.
47 Arya S, Duhan J, Tewari S, et al. Healing of apical periodontitis after nonsurgical treatment in patients with type 2 diabetes[J]. J Endod, 2017, 43(10): 1623-1627.
48 Uğur Aydın Z, Ocak MG, Bayrak S, et al. The effect of type 2 diabetes mellitus on changes in the fractal dimension of periapical lesion in teeth after root canal treatment: a fractal analysis study[J]. Int Endod J, 2021, 54(2): 181-189.
49 Laukkanen E, Vehkalahti MM, Kotiranta AK. Impact of systemic diseases and tooth-based factors on outcome of root canal treatment[J]. Int Endod J, 2019, 52(10): 1417-1426.
50 Martinho JP, Coelho A, Oliveiros B, et al. Impairment of the angiogenic process may contribute to lower success rate of root canal treatments in diabetes mellitus[J]. Int Endod J, 2021, 54(10): 1687-1698.
51 Saghiri MA, Karamifar K, Fakharzadeh A, et al. Effect of diabetes on tubular density and push-out bond strength of mineral trioxide aggregate to dentin[J]. J Endod, 2020, 46(11): 1584-1591.
52 Saghiri MA, Aminsobhani M, Gutmann JL, et al. Effect of diabetes on rotary instrumentation of dentin[J]. J Endod, 2021, 47(8): 1301-1307.
53 Wang S, Wang X, Bai F, et al. Effect of endodontic treatment on clinical outcome in type 2 diabetic patients with apical periodontitis[J]. Heliyon, 2023, 9(3): e13914.
[1] Wu Sijia,Shu Chang,Wang Yang,Wang Yuan,Deng Shuli,Wang Huiming.. Effect and research progress on root canal infection management of regenerative endodontic procedure in immature permanent teeth [J]. Int J Stomatol, 2023, 50(4): 388-394.
[2] Yang Xiaoyu,Yuan Quan.. Research progress on the role of extravascular fibrinogen deposition in mucosal diseases [J]. Int J Stomatol, 2023, 50(4): 457-462.
[3] Chen Yifei,Zhang Binjing,Feng Shuqi,Xu Rui,Yang Shuxian,Li Yuqing. Effects of flavonoids on oral microorganisms and its mechanism [J]. Int J Stomatol, 2023, 50(2): 210-216.
[4] Ye Yulin,Jiang Liting,Gao Yiming.. Role of autophagy in salivary glands of Sjögren’s syndrome [J]. Int J Stomatol, 2022, 49(5): 556-560.
[5] Fan Yu,Cheng Lei. Smoking affects the oral microenvironment and its role in the progression of dental caries [J]. Int J Stomatol, 2021, 48(5): 609-613.
[6] Li Shijia,Chen Qiuyu,Zou Jing,Huang Ruijie. Effect of nicotine on the growth of oral bacteria in single or mixed species [J]. Int J Stomatol, 2021, 48(3): 305-311.
[7] Zhang Mingshuang,Ba Te,Wang Wenbiao. Research progress on oral microorganisms affect Alzheimer’s disease [J]. Int J Stomatol, 2020, 47(1): 102-108.
[8] Pengfei Zhao,Qi Wang. Research progress on the etiology and therapy of bone defect during dental implantation under diabetic condition [J]. Inter J Stomatol, 2019, 46(2): 244-248.
[9] Liu Dan, Ren Biao, Cheng Lei.. Research development of silver nanoparticle on prevention and treatment of oral infectious disease [J]. Inter J Stomatol, 2018, 45(4): 408-413.
[10] Xiong Yi, Gong Ping, Wu Yingying. Establishment of diabetic mouse model with conditional knockout of FoxO1 in osteoblasts [J]. Inter J Stomatol, 2018, 45(2): 170-176.
[11] Yi Xiaowei, Huang Dingming, Zhang Lan. Pathogenesis and clinical management of apical periodontitis in diabetic patients [J]. Inter J Stomatol, 2018, 45(2): 214-218.
[12] Zhang Peng, Ding Yi, Wang Qi. Research on the role of inflammaging in diabetes mellitus-associated periodontitis [J]. Inter J Stomatol, 2017, 44(6): 664-668.
[13] Li Lin, Wang Dan, Zhao Manzhu, Tang Ming. Research progress on the correlation between chronic periodontitis and neurodegenerative diseases [J]. Inter J Stomatol, 2017, 44(5): 514-518.
[14] Wu Yingying, Gong Ping.. Effect of insulin on bone metabolism around implant in diabetic rats [J]. Inter J Stomatol, 2017, 44(2): 183-188.
[15] Wu Juan, Yao Min, Sun Weibin. Research progress on the potential use of gingival crevicular blood for finger stick blood screening in patients with diabetes mellitus [J]. Inter J Stomatol, 2016, 43(4): 486-489.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .