STOMATOLOGY EDU JOURNAL

ISSN(print) 2360-2406; ISSN(on-line) 2502-0285; ISSN-L 2360-2406

GINGIVAL INFLAMMATION AS A SIGN OF DIABETIC SYSTEMIC CHRONIC COMPLICATIONS

Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder and the high level of blood glucose has profound effects on various systems of the human body. DM increases the risk of periodontal disease and the severe periodontal disease often coexists in diabetic patients with poor glycemic control. The aim of the study was to analyse periodontal health in patients with diabetes mellitus type 2 related to diabetic complications and glycohemoglobin A1c values. Methodology: One hundred patients with periodontitis and type 2 DM participated in the study. According to the glycohemoglobin A1c value they were divided in 4 groups: group 1 (4%-6% normal), group 2 (6.1%-7% good), group 3 (7.1%-8% moderately poor), group 4 (> 8% poor metabolic control). The presence of chronic systemic microvascular diabetic complications (retinopathy, nephropathy and neuropathy) was recorded and periodontal assessments (Plaque, Gingival, Calculus and Periodontal Disease Index) performed. The results were statistically analysed using MS Office Excel, program SPSS, 15.0 version. Results: Gingival index values depended on the level of HbA1c values and higher values of the Gingival and Periodontal Disease Index were noticed as the value of glycohemoglobin A1c was rising (p<0,001). Gingival index values were higher in diabetics with diabetic chronic microvascular complications (p<0.001). Conclusion: It is observed that pronounced gingival inflammation in diabetics is associated with systemic diabetic complications and poor glycemic control. Keywords: diabetes mellitus, glycohemoglobin A1c, diabetic complications, gingival inflammation, periodontitis. ABSTRACT Received: April 14, 2016 Accepted: April 25, 2016 Available online: May 05, 2016 Cite this article: Obradović RR , Mitić AD, Kesić LG, Petrović AS, Pejčić AS, Petrović MS. Gingival inflammation as a sign of diabetic systemic chronic complications. Stoma Edu J. 2016;3(2):200-204. Radmila R Obradović1a*, Aleksandar D Mitić2b, Ljiljana G Kesić1c, Ana S Pejčić1d, Kosta M Todorović3e,Milica S Petrović1f 1 Department of Periodontology and Oral Medicine, Faculty of Medicine, Niš University, Serbia 2 Department of Dental Pathology and Endodontic, Faculty of Medicine, Niš University, Serbia 3 Department of Oral Surgery, Faculty of Medicine, Niš University, Serbia a DDS, PhD, Assistant Professor b DDS, PhD, Professor c DDS, PhD, Professor d DDS, PhD, Assistant Professor e DDS, Assistant f DDS, Postdoctoral Student *Corresponding author: Assistant Professor Radmila Obradović, DDS, PhD Faculty of Medicine, University of Niš 81, Dr Zoran Đinđić Blvd, 18000 Niš, SERBIA Tel: +381-64-235-9595; Fax: +381-18-42-38-770, e-mail: dr.rada@yahoo.com 1. Introduction Diabetes mellitus (DM) is a chronic metabolic disorder caused by the ineffectiveness of the insulin produced or by deficiency in production of insulin by the pancreas. Among diabetic patients over 45 years old, more than 95% patients have type 2 DM1. The high level of glucose present in the blood has profound effects on various systems of the human body1. The determination of glycohemoglobin A1c (HbA1c) levels provides an estimate of the average blood glucose level over the preceding one to three months. The higher average blood glucose levels reflect in higher HbA1c values2 . HbA1c level is of major clinical values in assessment diabetes prognosis and correlates well with the development of diabetic complications. The recommended HbA1c target value for people with diabetes mellitus is <7.0% and achieving this goal is very difficult3. DM significantly increases the prevalence, severity, and rate of progression of periodontal disease, and periodontal disease is 201 recognized as one of the complications of DM4-8. What is less clear is the impact of periodontal disease on glycemic control of DM and the mechanisms through which this occurs. Some authors suggest that an intensive gingival inflammation relate to poor glycemic control and multiple diabetic complications7-11. Periodontal disease may be more frequent and severe in diabetic individuals with more systemic complications. The evidence suggests that mechanisms which account for the development of systemic diabetic complications might also be crucial in the pathogenesis of increased periodontal destruction in DM12,13. The diabetic state impairs the synthesis of collagen and glycosaminoglycan, enhances crevicular fluid collagenolytic activity which lead to the loss of periodontal fibres and loss of the alveolar supporting bone14,15. This predisposes to chronic inflammation, progressive tissue breakdown and diminished tissue repair capacity. These mechanisms cause periodontal tissue breakdown and loosening of the teeth14-16. The increased activity of periodontal disease in diabetic patients does not correlate with levels of plaque and calculus which do not have higher values in diabetic patients. Collectively, the evidence supports the theory that there is a relationship between the two diseases, especially in patients with poorly controlled DM17. This proposed dual pathway of tissue destruction suggests that control of DM is necessary for achieving long-term control of periodontal disease7-11. 2. The aim of the study The aim of the study was to analyze periodontal health in patients with diabetes mellitus type 2 related to diabetic complications and HbA1c values. 3. Methodology 3.1. Study design and subjects This clinical study was carried out as a joint collaboration between Department of Endocrinology and Department of Periodontology and Oral medicine, Niš University, Faculty of Medicine. The study protocol was reviewed and approved by the Niš University Faculty of Medicine Institutional Ethical Committee (identification number 01-2800-7) and in accordance with the Helsinki Declaration of 1975, as revised in 2000. 3.2. Subjects Patients with periodontitis and DM were selected from the pool of followed patients at the Department of Endocrinology, Niš University Medical Center. After the patient history was taken, patients who had acute systemic or oral disease, autoimmune diseases, hemorrhagic disorders, who had undergone antibiotic and corticosteroid therapy in the last three months, as well as patients who had periodontal treatment in the last three months were not included in the study. One hundred patients with periodontal disease and type 2 DM, 48 (48%) women and 52 (52%) men, the mean age 62.57±8.57 years participated in the study. The HbA1c level was taken from the patient records. In the analysis according to the HbA1c values patients were divided in four groups: group 1 (4%-6% HbA1c; normal metabolic control), group 2 (6.1%-7% HbA1c; good metabolic control), group 3 (7.1%-8% HbA1c; moderate poor metabolic control), group 4 (> 8% HbA1c; poor metabolic control). The presence of chronic systemic microvascular diabetic complications (retinopathy, nephropathy and neuropathy) was recorded from patients records, and according to presence of these complications patients were divided in groups: patients with chronic systemic DM complications (group A) and patients without chronic systemic DM complications (group B). 3.3. Oral examination protocol The periodontal assessments were performed by a single examiner on four sites per tooth (mesiobuccal, disto-buccal, mesio-lingual, disto-lingual) for all (third molars excluded) fully erupted permanent teeth, using a manual periodontal probe. Using the tip of the periodontal probe inserted into the pocket with constant probing force the following were evaluated: Plaque index (PI)18, Gingival Index (GI)19, Calculus index (Cal)20, and Periodontal Disease Index (PDI)21. Afterwards, all of the patients received oral hygiene instructions and full-mouth scaling and root planning. 3.4. Diabetes-related variables The following information were collected from medical records: sex, duration of DM (years since diagnosis) and patient age. For the metabolic assessment, the HbA1c level was calculated from the patient records. 3.5. Analytical methods The statistical analysis was performed using SPSS software program and parameters were shown as mean values (X) and standard deviations (SD). Student t-test, Leven method, Tukey HSD test and Dunnett T3 test were used for analysis of statistically important difference between mean values of two groups. The results are shown tabularly using MS Office Excel, program SPSS, 15.0 version. 4. Results The study population included patients with DM type 2 aged 22-83 years, 51 women and 49 men. Mean HbA1c value was 8.70±0.45% and the mean DM duration 14.68±3.43 years. Comparing mean values and standard deviations (X±SD) of PI, Izk, Ikon, Gi and PDI indexes according to HbA1c values, ANOVA analysis showed that Gi values depended on the level of HbA1c values (p<0,001). Higher values of investigated indexes were noticed as the value of HbA1c was rising (p<0,001) (Table 1). Comparing mean values and standard deviations (X±SD) of PI, Izk, Ikon, Gi and PDI indexes according to presence of chronic systemic DM complications, it was noticed that only Gi values were higher in the group with chronic systemic DM complications (retinopathy, nephropathy and neuropathy) (t=5.42, p<0.001) (Table 2). GINGIVAL INFLAMMATION AS A SIGN OF DIABETIC SYSTEMIC CHRONIC COMPLICATIONS 202 STOMA.EDUJ (2016) 3 (2) 5. Discussion DM and periodontal disease are common chronic diseases in adults22,23. The general opinion is that there is no effect of gender on elevated blood glucose in diabetic patients, as noticed in this study, whereas both sexes were uniformly represented24. Diabetic patients with poor metabolic control are at a high risk for a poor periodontal prognosis7,8. Most studies suggest that the situation for periodontal disease is similar to that for the other systemic complications of DM5,7,8. The metabolic control in diabetic patients is an important variable in the onset and progression of periodontal disease and chronic systemic DM complications5. Lalla et al.24 noticed that HbA1c was positively and significantly correlated with gingival bleeding. The presence of periodontal pockets and attachment loss were not significantly correlated with HbA1c higher values in diabetic patients. These findings suggest that changes in the periodontal microvasculature are related to the level of metabolic control. The results of this investigation were similar to literature data25. The ‘‘poor metabolic control’’ shown through the high values of HbA1c clearly increases the risk of activation of gingival inflammation and higher values of Gi index are present as the value of HbA1c was rising (p<0,001). Salvi26 investigated diabetics with mean HbA1c of 8.1%, and concluded that in diabetic patients with ‘‘poor metabolic control’’ the bleeding tendencies were higher than in those with lower values of HbA1c. Similar findings were noticed in the present investigation. Mean Gi values in groups with “moderately poor” and “poor metabolic control” were higher comparing to the values in group with “good metabolic control” (p<0,05). Lalla E et al.24 measured attachment loss and gingival bleeding separately, and similarly as previous investigators noticed that HbA1c was positively and significantly correlated with gingival bleeding, but not with attachment loss alone24,27. Similar findings were noticed in the present investigation where mean Gi values in groups with “moderate poor” and “poor metabolic control” were higher comparing to group with “good metabolic control” (p<0,05). Some authors emphasize that an intensive gingival inflammation suggests the existence of poor glycemic control and multiple systemic diabetic complications7-11. Similar noticed in the present study where diabetics with chronic systemic diabetic complications also had higher values of Gi. The evidence suggests that mechanisms which account for the development of systemic diabetic chronic microvascular complications might also be operating in the pathogenesis of increased gingival inflammation in DM12,13. Potentially a number of factors could contribute to the periodontal disease in DM (oral microflora, phagocytic and connective-tissue defects) and exploring the complex pathogenic mechanisms underlying these associations was beyond the scope of this study. Further studies with larger sample sizes are needed to investigate the pathogenic mechanisms between gingival inflammation and systemic diabetic chronic complications. The general opinion is that diabetic patients exhibit poorer periodontal health and poorer therapeutic response than systemically health patients28. Good glycemic control might be essential in the prevention of periodontal complications in patients with DM20,29,30. During routine dental checkup, dentists detecting pronounced gingival inflammation in patients with DM can suspect the presence of undiagnosed diabetic chronic complications and refer a patient GINGIVAL INFLAMMATION AS A SIGN OF DIABETIC SYSTEMIC CHRONIC COMPLICATIONS Table 1. Mean values and standard deviations (X±SD) of PI, Izk, Ikon, Gi and PDI indexes and statistically important differences between groups according to HbA1c values Table 2. Mean values and standard deviations (X±SD) of PI, Izk, Ikon, Gi and PDI values and statistically important differences between groups according to chronic systemic DM complications Groups according to HbA1 c N Pl Izk Ikon Gi PDI 1 (4%-6%) / / / / / 2 (6.1%-7%) 22 2.33±0.58 2.00±0.00 2.67±0.58 1,00±0,00 4.68±0.79 3 (7.1%-8%) 16 2.57±0.53 1.86±0.69 2.57±0.53 1,75±0,46def* 5.00±0.00 4 (> 8%) 62 2.28±0.68 1.98±0.66 2.58±0.55 2,00±0,00 5.25±0.46 a -1vs2, b-1vs3, c –1vs4, d-2vs3, e-2vs4, f–3vs4; * – p<0,05, ** – p<0,01, *** – p<0,001 a -AvsB gr, * – p<0.05, ** – p<0.01, *** – p<0.001 Groups according to DM complications N Pl Izk Ikon Gi PDI A (with DM complications) 70 2.23±0.69 1.63±0.69 1.66±0.76 1.92±0.27*** 4.91±0.61 B (without DM complications) 30 1.87±0.74 1.47±0.52 1.73±0.96 1.64±0.50 4.53±0.83 203 to an endocrinologist for prompt treatment of the underlying disease and DM complications. For proper dental care the dentist should be aware of the diabetic status of each patient. Information on the levels of HbA1c over a longer period of time and the presence/absence of any diabetic complications is needed in assessing periodontal prognosis and the need for periodontal therapy on individual basis. Close collaboration between the patient, the primary health care and oral health professionals, and application of new therapeutic modalities could be a way of improving the diabetic patient’s general and oral health7,8. 6. Conclusion It is observed that pronounced gingival inflammation in diabetics is associated with systemic diabetic chronic microvascular complications and poor glycemic control. As periodontal disease is a complex multifactorial disease related to DM, the prevention and control of periodontal disease must be considered an integral part of DM control. The findings in this study highlight a need to promote oral health in patients with DM as an integral component of total patient care. Acknowledgment This research was supported by a grant from the Serbian Ministry of Education and Science, No.175061. REFERENCES 1. Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, Cameron AJ, Dwyer T, Taylor HR, Tonkin AM, Wong TY, McNeil J, Shaw JE. Risk of cardiovascular and all-cause mortality in Individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007;116(2):151- 157. 2. Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE. Defining the relationship between plasma glucose and HbA1c: analysis of glucose profiles and HbA1c in the Diabetes Control and Complications Trial. Diabetes Care. 2002;25 (2):275-278. 3. Koro CE, Bowlin SJ, Bourgeois N, Fedder DO. Glycemic control from 1988 to 2000 among U.S. adults diagnosed with type 2 diabetes: a preliminary report. Diabetes Care. 2004;27(1):17-20. 4. King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontol. 2008;79(8Suppl):1527-1534. doi: 10.1902/jop.2008.080246. 5. Taylor G. Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective. Ann Periodontol. 2001;6(1):99-112. 6. Löe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16(1):329-334. 7. Mealey BL, Rethman MP. Periodontal disease and diabetes mellitus. Bidirectional relationship. Dent Today. 2003; 22(4):107- 113. 8. Southerland JH, Taylor GW, Offenbacher S. Diabetes and periodontal infection: Making the connection. Clin Diabetes 2005;23(4):171-178. 9. Karjalainen KM, Knuuttila ML, von Dickhoff KJ. Association of the severity of periodontal disease with organ complications in type 1 diabetic patients. J Periodontol. 1994; 65(11):1067-1072. 10. Mealey BL, Oates TW; American Academy of Periodontology. Diabetes mellitus and periodontal diseases. J Periodontol. 2006;77(8):1289-1303. 11. Scannapieco FA, Panesar M. Periodontitis and chronic kidney disease. J Periodontol. 2008;79(9):1617-1619. doi: 10.1902/ jop.2008.080313. 12. Lalla E, Lamster IB, Feit M, Huang L, Spessot A, Qu W, Kislinger T, Lu Y, Stern DM, Schmidt AM. Blockade of RAGE suppresses periodontitis associated bone loss in diabetic mice. J Clin Invest 2000;105(8):1117-1124. 13. Hudson BI, Bucciarelli LG, Wendt T, Sakaguchi T, Lalla E, Qu W, Lu Y, Lee L, Stern DM, Naka Y, Ramasamy R, Yan SD, Yan SF, D’Agati V, Schmidt AM. Blockade of receptor for advanced glycation endproducts: a new target for therapeutic intervention in diabetic complications and inflammatory disorders. Arch Biochem Biophys. 2003;419(1):80-88. 14. Liu R, Bal HS, Desta T, Krothapalli N, Alyassi M, Luan Q, Graves DT. Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation. J Dent Res. 2006;85(6):510-514. 15. Lappin DF, Eapen B, Robertson D, Young J, Hodge PJ. Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitus. J Clin Periodontol. 2009;36(8):634-641. 16. Iacopino AM. Periodontitis and diabetes interrelationships: the role of inflammation. Ann Periodontol. 2001;6(1):125-137. 17. Katz J. Elevated blood glucose levels in patients with severe periodontal disease. J Clin Periodontol. 2001;28(7):710-712. 18. Silness J, Löe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scandinav. 1964;22(1):121-135. 19. Löe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scandinav. 1963;21(6):533- 551. 20. Morrison EC, Ramfjord SP, Hill RW. Short-term effects of initial, nonsurgical periodontal treatment (hygienic phase). J Clin Periodontol. 1980;7(3):199-211. 21. Ramfjord SP. The Periodontal Disease Index (PDI). J Periodontol. 1967;38(6):Suppl:602-610. 22. Page RC, Beck JD. Risk assessment for periodontal diseases. Int Dent J. 1997;47(2):61-87. 23. Güneri P, Unlü F, Yeşilbek B, Bayraktar F, Kokuludağ A, Hekimgil M, Boyacioğlu H. Vascular endothelial growth factor in gingival tissues and crevicular fluids of diabetic and healthy periodontal patients. J Periodontol. 2004;75(1):91-97. 24. Lalla E, Cheng B, Lal S, Kaplan S, Softness B, Greenberg E, Goland RS, Lamster IB. Diabetes-related parameters and periodontal conditions in children. J Periodontal Res. 2007;42(4):345-349. 25. Rabelo SB, Villaverde AB, Nicolau R, Salgado MC, Melo Mda S, Pacheco MT. Comparison between wound healing in induced diabetic and nondiabetic rats after low-level laser therapy. Photomed Las Surg. 2006; 24(4):474-479. 26. Salvi GE, Kandylaki M, Troendle A, Persson GR, Lang NP. Experimental gingivitis in type 1 diabetics a controlled clinical and microbiological study. J Clin Periodontol. 2005;32(3):310-316. 27. Manfredi M, McCullough MJ, Vescovi P, Al-Kaarawi ZM, Porter SR. Update on diabetes mellitus and related oral diseases. Oral Dis. 2004;10(4):187-200. 28. Teeuw WJ, Gerdes VE, Loos BG. Effect of periodontal treatment on glycemic control of diabetic patients. A systematic review and meta-analysis. Diabetes Care. 2010;33(2):421-7. doi: 10.2337/dc09-1378. 29. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986. 30. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131): 837-853. GINGIVAL INFLAMMATION AS A SIGN OF DIABETIC SYSTEMIC CHRONIC COMPLICATIONS 204 STOMA.EDUJ (2016) 3 (2) CV Doctor Radmila Obradovic is an Assistant Professor at the Department of Oral Medicine and Periodontology, Dental Clinic, Faculty of Medicine, Niš University; Serbia. She is also a member of the Dental Clinic’s Ethical Committee and Medical Faculty’s Disciplinary Board. She is a member of the Serbian Medical Society and Serbian Oral Laser Society (SOLAS). She participated in national projects, many dental courses and conferences as a lecturer, and published many papers in dental and medical journals. DDS, PhD, Assistant Professor Department of Oral Medicine and Periodontology Dental Clinic, Faculty of Medicine Niš University, Serbia Questions Regarding diabetic periodontitis: qa. Mechanisms which account for the development of systemic diabetic complications might also be crucial in the pathogenesis of increased periodontal destruction; qb. Diabetes mellitus has no influence on periodontitis; qc. Periodontitis has no influence on diabetes mellitus; qd. Diabetes mellitus and periodontitis have no influence on each other. Regarding this study: qa. 100 patients with periodontal disease and type 2 DM participated in this study; qb. 100 patients with periodontal disease and type 1 DM participated in this study; qc. 100 patients with periodontal disease and gestational DM participated in this study; qd. Patients with DM did not participate in this study. Regarding to the glycohemoglobin A1c value patients were divided in: qa. 4 groups; qb. 3 groups; qc. 2 groups; qd. 5 groups. Regarding gingival inflammation and diabetic microvascular complications: qa. Pronounced gingival inflammation in diabetics is associated with systemic diabetic chronic microvascular complications and poor glycemic control; qb. Pronounced gingival inflammation in diabetics is not associated with systemic diabetic chronic microvascular complications and poor glycemic control; qc. Systemic diabetic chronic microvascular complications have no influence on gingival health; qd. Glycemic control has no influence on gingival health. Radmila Obradovic GINGIVAL INFLAMMATION AS A SIGN OF DIABETIC SYSTEMIC CHRONIC COMPLICATIONS

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