Influence of type 2 diabetes on local production of inflammatory molecules in adults with and without chronic periodontitis: a cross-sectional study

BMC Oral Health

Manal Mustafa²  Salah O. Ibrahim³  Kamal Mustafa³  Anne N. Åstrøm³  Mutaz F. Ahmed⁴  Shaza B. Idris³  Hasaan G. Mohamed¹ 

[1] Department of Oral Rehabilitation, Faculty of Dentistry, University of Khartoum, Khartoum, Sudan;Oral Health Competence Center in Western Norway, Hordaland, Bergen, Norway;Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Årstadveien 19, Bergen, 5009, Norway;Hamad Medical Corporation, Doha, Qatar

关键词: Cytokines;    Gingival crevicular fluid;    Inflammation;    Chronic periodontitis;    Diabetes mellitus;   

Others  :  1221119
DOI  :  10.1186/s12903-015-0073-z

 received in 2015-03-31, accepted in 2015-07-16,  发布年份 2015

【 摘 要 】

Background

Pathological changes in periodontal tissues are mediated by the interaction between microorganisms and the host immune-inflammatory response. Hyperglycemia may interfere with this process. The aim of this study was to compare the levels of 27 inflammatory molecules in the gingival crevicular fluid (GCF) of patients with type 2 diabetes, with and without chronic periodontitis, and of chronic periodontitis subjects without diabetes. A putative correlation between glycated haemoglobin (HbA1c) and levels of the inflammatory molecules was also investigated.

Methods

The study population comprised a total of 108 individuals, stratified into: 54 with type 2 diabetes and chronic periodontitis (DM + CP), 30 with chronic periodontitis (CP) and 24 with type 2 diabetes (DM). Participants were interviewed with the aid of structured questionnaire. Periodontal parameters (dental plaque, bleeding on probing and periodontal pocket depth) were recorded. The GCF levels of the 27 inflammatory molecules were measured using multiplex micro-bead immunoassay. A glycated haemoglobin (HbA1c) test was performed for patients with diabetes by boronate affinity chromatography.

Results

After adjustment for potential confounders, the DM + CP group had higher levels of IL-8 and MIP-1β, and lower levels of TNF-α, IL-4, INF-γ, RANTES and IL-7 compared to the CP group. Moreover, the DM + CP group had lower levels of IL-6, IL-7 and G-CSF compared to the DM group. The DM group had higher levels of IL-10, VEGF, and G-CSF compared to the CP group. The levels of MIP-1α and FGF were lower in diabetes patients (regardless of their periodontal status) than in chronic periodontitis subjects without diabetes. Diabetes patients (DM + CP and DM) had higher Th-2/Th-1 ratio compared to the CP group. HbA1c correlated positively with the pro-inflammatory cytokines (Pearson correlation coefficient = 0.27, P value: 0.02).

Conclusion

Type 2 diabetes and chronic periodontitis may influence the GCF levels of inflammatory molecules synergistically as well as independently. Type 2 diabetes was associated with high Th-2/Th-1 ratio, and modulated the local expression of molecules involved in the anti-inflammatory and healing processes.

【 授权许可】

   
2015 Mohamed et al.

【 图 表 】

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【 参考文献 】

• [1]Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998; 15(7):539-553.
• [2]American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014, 37 Suppl 1:S81-90.
• [3]International Diabetes Federation. IDF Diabetes Atlas update poster, 6th edn. Brussels, Belgium. International Diabetes Federation 2014.
• [4]Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010; 87:4-14.
• [5]Abdelgadir M, Elbagir M, Eltom M, Berne C. The influence of glucose self-monitoring on glycaemic control in patients with diabetes mellitus in Sudan. Diabetes Res Clin Pract. 2006; 74(1):90-94.
• [6]Sima C, Glogauer M. Diabetes mellitus and periodontal diseases. Curr Diab Rep. 2013; 13(3):445-452.
• [7]Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005; 366(9499):1809-1820.
• [8]Armitage GC. Periodontal diagnoses and classification of periodontal diseases. Periodontol 2000. 2004; 34:9-21.
• [9]Preshaw PM, Taylor JJ. How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? J Clin Periodontol. 2011; 38 Suppl 11:60-84.
• [10]Kornman KS. Mapping the pathogenesis of periodontitis: a new look. J Periodontol. 2008; 79(8 Suppl):1560-1568.
• [11]Hanes PJ, Krishna R. Characteristics of inflammation common to both diabetes and periodontitis: are predictive diagnosis and targeted preventive measures possible? The EPMA journal. 2010; 1(1):101-116.
• [12]Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Periodontol. 2013; 84(4 Suppl):S113-134.
• [13]King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontol. 2008; 79(8 Suppl):1527-1534.
• [14]Abbass MM, Korany NS, Salama AH, Dmytryk JJ, Safiejko-Mroczka B. The relationship between receptor for advanced glycation end products expression and the severity of periodontal disease in the gingiva of diabetic and non diabetic periodontitis patients. Arch Oral Biol. 2012; 57(10):1342-1354.
• [15]Nathan D, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia. 2007; 50(11):2239-2244.
• [16]Lamster IB, Ahlo JK. Analysis of gingival crevicular fluid as applied to the diagnosis of oral and systemic diseases. Ann N Y Acad Sci. 2007; 1098:216-229.
• [17]Griffiths GS. Formation, collection and significance of gingival crevice fluid. Periodontol 2000. 2003; 31:32-42.
• [18]Mohamed HG, Idris SB, Ahmed MF, Bøe OE, Mustafa K, Ibrahim SO, et al. Association between Oral Health Status and Type 2 Diabetes Mellitus among Sudanese Adults: A Matched Case-Control Study. PloS one. 2013;8(12):e82158.
• [19]Diagnosis and classification of diabetes mellitus. Diabetes Care. 2008; 31 Suppl 1:S55-60.
• [20]Little RR, Roberts WL. A review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Technol. 2009; 3(3):446-451.
• [21]Silness J, Loe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta odontologica Scandinavica. 1964; 22:121-135.
• [22]Katagiri S, Nagasawa T, Kobayashi H, Takamatsu H, Bharti P, Izumiyama H, et al. Improvement of glycemic control after periodontal treatment by resolving gingival inflammation in type 2 diabetic patients with periodontal disease. J Diabetes Invest. 2012;3(4):402–9.
• [23]Eke PI, Page RC, Wei L, Thornton-Evans G, Genco RJ. Update of the case definitions for population-based surveillance of periodontitis. J Periodontol. 2012; 83(12):1449-1454.
• [24]Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960; 20:37-46.
• [25]Houser B. Bio-Rad's Bio-Plex(R) suspension array system, xMAP technology overview. Arch Physiol Biochem. 2012; 118(4):192-196.
• [26]Thunell DH, Tymkiw KD, Johnson GK, Joly S, Burnell KK, Cavanaugh JE, et al. A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy. J Periodontal Res. 2010;45(1):148–52.
• [27]Dinarello CA. Proinflammatory cytokines. Chest. 2000; 118(2):503-508.
• [28]Duarte PM, de Oliveira MC, Tambeli CH, Parada CA, Casati MZ, Nociti FHJr. Overexpression of interleukin-1beta and interleukin-6 may play an important role in periodontal breakdown in type 2 diabetic patients. J Periodontal Res. 2007;42(4):377–81.
• [29]Atieh MA, Faggion CMJr, Seymour GJ. Cytokines in patients with type 2 diabetes and chronic periodontitis: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2014;104(2):e38–45.
• [30]Correa FO, Goncalves D, Figueredo CM, Gustafsson A, Orrico SR. The short-term effectiveness of non-surgical treatment in reducing levels of interleukin-1beta and proteases in gingival crevicular fluid from patients with type 2 diabetes mellitus and chronic periodontitis. J Periodontol. 2008; 79(11):2143-2150.
• [31]Navarro-Sanchez AB, Faria-Almeida R, Bascones-Martinez A. Effect of non-surgical periodontal therapy on clinical and immunological response and glycaemic control in type 2 diabetic patients with moderate periodontitis. J Clin Periodontol. 2007; 34(10):835-843.
• [32]Duarte PM, Bezerra JP, Miranda TS, Feres M, Chambrone L, Shaddox LM. Local levels of inflammatory mediators in uncontrolled type 2 diabetic subjects with chronic periodontitis. J Clin Periodontol. 2014; 41(1):11-18.
• [33]Engebretson SP, Hey-Hadavi J, Ehrhardt FJ, Hsu D, Celenti RS, Grbic JT, Lamster IB. Gingival crevicular fluid levels of interleukin-1beta and glycemic control in patients with chronic periodontitis and type 2 diabetes. J Periodontol. 2004; 75(9):1203-1208.
• [34]Kinane DF, Preshaw PM, Loos BG. Host-response: understanding the cellular and molecular mechanisms of host-microbial interactions--consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol. 2011; 38 Suppl 11:44-48.
• [35]Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther. 2006; 8 Suppl 2:S2. BioMed Central Full Text
• [36]Hosokawa Y, Shindo S, Hosokawa I, Ozaki K, Matsuo T. IL-6 trans-signaling enhances CCL20 production from IL-1beta-stimulated human periodontal ligament cells. Inflammation. 2014; 37(2):381-386.
• [37]Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994; 83(1):113-118.
• [38]Khosravi R, Ka K, Huang T, Khalili S, Nguyen BH, Nicolau B, et al. Tumor necrosis factor- alpha and interleukin-6: potential interorgan inflammatory mediators contributing to destructive periodontal disease in obesity or metabolic syndrome. Mediators Inflamm. 2013;2013:728987.
• [39]Javed F, Al-Askar M, Al-Hezaimi K. Cytokine profile in the gingival crevicular fluid of periodontitis patients with and without type 2 diabetes: a literature review. J Periodontol. 2012; 83(2):156-161.
• [40]Ribeiro FV, de Mendonça AC, Santos VR, Bastos MF, Figueiredo LC, Duarte PM. Cytokines and bone-related factors in systemically healthy patients with chronic periodontitis and patients with type 2 diabetes and chronic periodontitis. J Periodontol. 2011; 82(8):1187-1196.
• [41]Chamberlain CS, Leiferman EM, Frisch KE, Wang S, Yang X, Brickson SL, et al. The influence of interleukin-4 on ligament healing. Wound Repair Regen. 2011;19(3):426–35.
• [42]Baggiolini M, Dewald B, Moser B. Human chemokines: an update. Annu Rev Immunol. 1997; 15:675-705.
• [43]Longo PL, Artese HP, Rabelo MS, Kawamoto D, Foz AM, Romito GA, et al. Serum levels of inflammatory markers in type 2 diabetes patients with chronic periodontitis. J Appl Oral Sci. 2014;22(2):103–8.
• [44]Maurer M, von Stebut E. Macrophage inflammatory protein-1. Int J Biochem Cell Biol. 2004; 36(10):1882-1886.
• [45]Gemmell E, Carter CL, Seymour GJ. Chemokines in human periodontal disease tissues. Clin Exp Immunol. 2001; 125(1):134-141.
• [46]Sonmez AB, Castelnuovo J. Applications of basic fibroblastic growth factor (FGF-2, bFGF) in dentistry. Dent Traumatol. 2014; 30(2):107-111.
• [47]Barrientos S, Brem H, Stojadinovic O, Tomic-Canic M. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014; 22(5):569-578.
• [48]Moriya J, Ferrara N. Inhibiting the response to VEGF in diabetes. Sci Signal. 2014; 7(307):e1.
• [49]Sakallioglu EE, Aliyev E, Lutfioglu M, Yavuz U, Acikgoz G. Vascular endothelial growth factor (VEGF) levels of gingiva and gingival crevicular fluid in diabetic and systemically healthy periodontitis patients. Clin Oral Investig. 2007; 11(2):115-120.
• [50]Guneri P, Unlu F, Yesilbek B, Bayraktar F, Kokuludag A, Hekimgil M, et al. Vascular endothelial growth factor in gingival tissues and crevicular fluids of diabetic and healthy periodontal patients. J Periodontol. 2004;75(1):91–7.
• [51]Van Dyke TE, van Winkelhoff AJ. Infection and inflammatory mechanisms. J Clin Periodontol. 2013; 40 Suppl 14:S1-7.
• [52]Goswami R, Kaplan MH. A brief history of IL-9. J Immunol. 2011; 186(6):3283-3288.
• [53]Van Dyke TE. Cellular and molecular susceptibility determinants for periodontitis. Periodontol 2000. 2007; 45:10-13.
• [54]Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010; 89(12):1349-1363.
• [55]Wu Y, Liu F, Zhang X, Shu L. Insulin modulates cytokines expression in human periodontal ligament cells. Arch Oral Biol. 2014; 59(12):1301-1306.
• [56]Preshaw PM, Foster N, Taylor JJ. Cross-susceptibility between periodontal disease and type 2 diabetes mellitus: an immunobiological perspective. Periodontol 2000. 2007; 45:138-157.
• [57]Fernandez y Mostajo M, Zaura E, Crielaard W, Beertsen W. Does routine analysis of subgingival microbiota in periodontitis contribute to patient benefit? Eur J Oral Sci. 2011; 119(4):259-264.
• [58]Kinney JS, Morelli T, Oh M, Braun TM, Ramseier CA, Sugai JV, et al. Crevicular fluid biomarkers and periodontal disease progression. J Clin Periodontol. 2014;41(2):113–20.
• [59]Petropoulos G, McKay IJ, Hughes FJ. The association between neutrophil numbers and interleukin-1alpha concentrations in gingival crevicular fluid of smokers and non-smokers with periodontal disease. J Clin Periodontol. 2004; 31(5):390-395.
• [60]Burstyn I, Yang Y, Schnatter AR. Effects of non-differential exposure misclassification on false conclusions in hypothesis-generating studies. Int J Environ Res Public Health. 2014; 11(10):10951-10966.
• [61]Zhong Y, Slade GD, Beck JD, Offenbacher S. Gingival crevicular fluid interleukin-1beta, prostaglandin E2 and periodontal status in a community population. J Clin Periodontol. 2007; 34(4):285-293.
• [62]Lopez R, Dahlen G, Baelum V. Subgingival microbial consortia and the clinical features of periodontitis in adolescents. European journal of oral sciences. 2011; 119(6):455-462.
• [63]Zimmermann H, Hagenfeld D, Diercke K, El-Sayed N, Fricke J, Greiser KH, et al. Pocket depth and bleeding on probing and their associations with dental, lifestyle, socioeconomic and blood variables: a cross-sectional, multicenter feasibility study of the German National Cohort. BMC oral health. 2015;15:7.