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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES - NGUYEN VAN MINH Study on clinical, paraclinical features and treatment of periodontitis in patients with type diabetes by diode laser Speciality: Oral and Maxillofacial Code: 62720601 ABSTRACT OF MEDICAL PHD THESIS HANOI – 2022 THE THESIS WAS DONE IN: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Supervisor: Assoc Prof PhD Ta Anh Tuan Prof PhD Hoang Tu Hung Reviewer: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year 2022 The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences INTRODUCTION Today, chronic diseases are the leading causes of death and disability worldwide One of these chronic non-communicated diseases with a rapid growth rate is diabetes, especially type diabetes Among the correlation between oral health status and systemic disease, periodontitis and diabetes have a strong two-way relationship It is the inflammatory immune response in the periodontal tissues that produces inflammatory mediators (Interleukin-1β, Interleukin-6, tumor necrosis factor α ) These mediators can cause destruction of periodontal tissues In patients with diabetes, hyperglycemia is associated with an immune response characterized by increased inflammatory cytokines such as tumor necrosis factor α (TNF-α), Interleukin-1(IL-1β), Interleukin-6 (IL-6) Scaling-root planning (SRP) is a basic, non-surgical treatment for periodontal therapy procedures However, this mechanical method is not effective enough; especially for periodontitis treatment in diabetic patients Adjunctive diode laser application in the treatment of periodontitis after SRP has obtained good results In the literature, the worldwide studies show that diode laser-assisted periodontitis treatment significantly reduces bacteria in periodontal pockets, improves clinical indicators (gingivitis, periodontal pocket depth, clinical attachment loss) and reduces inflammatory mediators in gingival and blood fluids In addition, periodontitis treatment in patients with diabetes has improved glycated hemoglobin (HbA1c) The aim of this thesis was : To study on clinical features, biochemical indicators, inflammatory immune factors in periodontitis patients with type diabetes To evaluate the results of periodontitis treatment with 810nm diode laser in periodontitis patients with type diabetes Chapter LITERATURE REVIEW 1.1 PERIODONTAL DISEASE 1.1.1 Periodontal anatomy Periodontal tissue is surrounded by teeth structures including gingiva, alveolar bone, periodontal ligament, and root cementum 1.1.2 Definition and classification of periodontal disease Periodontal disease is an inflammatory disease characterized by destruction of the soft and hard tissues that support the teeth, including the adhesion epithelium, periodontal ligaments, alveolar bone, and root cementum According to America Academy of Periodontology (AAP) in 1999, periodontal disease is classified into pathological groups 1.1.3 Diagnostic criteria for periodontitis According to CDC and AAP (2015): - Mild periodontitis: ≥ sites (different tooth), PD ≥ 4mm or ≥ sites (different tooth), CAL ≥ 3mm - Moderate periodontitis: ≥ sites (different tooth), 5mm≤ PD < 7mm or ≥ sites (different tooth), CAL ≥ 4mm - Severe periodontitis: ≥ sites (different tooth) CAL ≥ 5mm and ≥ site PD ≥ 5mm or PD ≥ 7mm 1.1.4 Periodontal Index examination - Plaque Index (PlI) - Gingival Index (GI) - Periodontal Pocket Depth (PD) - Clinical Attachment Loss (CAL) - Bleeding on Probing (BOP) 1.1.5 Periodontitis treatment Non-surgical treatment: initial treatment, supportive treatment and maintenance treatment Surgical treatment 1.2 DIABETIC DISEASE 1.2.1 Definition Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both (ADA- 2004) 1.2.2 Classification (ADA-2015) groups of DM: type diabetes, type diabetes, gestational diabetes, other specific diabetes 1.2.3 Diagnosing and monitoring diabetes According to ADA (2015), diabetes diagnosis is based on HbA1c more than 6.5% 1.3 THE RELATIONSHIP BETWEEN DIABETES AND PERIODONTITIS 1.3.1 Effects of diabetes on periodontal health Diabetes is a major risk factor for periodontitis through the following processes: Inflammatory process Advanced glycation end products (AGEs) Imbalance between bone resorption and bone formation (RANK/RANKL/OPG axis) 1.3.2 Impact of periodontitis on diabetes Periodontitis negatively affects glycemic control through inflammatory mediators including IL-1β, IL-6, and TNF-α These substances enter the circulation, causing the onset of a systemic inflammatory response Systemic inflammatory processes exacerbate diabetes status 1.4 OVERVIEW OF LASER AND DIODE LASER 1.4.1 Laser LASER: "Light Amplification by Stimulated Emission of Radiation” 1.4.2 Diode laser Diode laser (DL) is widely used in dental field such as soft tissue surgery (cutting, removing tissues), sterilization, teeth whitening, biological stimulation (increasing soft tissue healing, stimulates bone formation), facial pain relief In recent years, laser application to support periodontal treatment has been widely studied and applied 1.4.2.3 Interaction between laser and target tissues The laser light interacts with the target tissues (oral tissue) in four ways: absorption, penetration, reflection, and scattering 1.4.2.4 Application of diode laser in periodontal treatment Diode laser supports to periodontitis treatment after SRP according to the following effects: Removal of pathological epithelium in periodontal pockets Disinfection Inflammation reduction, bleeding prevention Biological stimulation, pain relief 1.5 RELEVANT RESEARCH WORLDWIDE AND IN VIETNAM Many worldwide studies showed that clinical features including GI, PD, CAL were improved, and inflammatory mediators and HbA1c were reduced after SRP treatment with diode laser application These clinical and subclinical parameters were better than those after SRP treatment without diode laser application In Vietnam, as our knowledge, there are no studies on treatment of periodontitis/diabetes with diode laser Chapter SUBJECTS AND METHODS 2.1 SUBJECT POPULATION The subject population of this study included patients with mild and moderate periodontitis/Type DM attempting outpatient treatment at Internal Medicine Clinic, Hue University of Medicine and Pharmacy Hospital 2.1.1 Inclusion criteria - Patients were diagnosed with type diabetes for at least year - At least 15 teeth left - No periodontal treatment in months up to the time of study - Do not use any antibiotics for months up to the time of study 2.1.2 Exclusion criteria - Severe periodontitis - Patients with cardiovascular diseases related to periodontal status such as atherosclerosis, coronary artery disease, stroke - Pregnant women - Smoking, obesity 2.2 METHODS 2.2.1 Study design: Controlled clinical trial intervention 2.2.2 Sample size The sample size was calculated according to the formula: ( ) ( ) ( ) ( ) p1 of 0.5 corresponding to 50% of the desired outcome ratio in the control group p2 of 0.75 corresponding to 75% of the desired outcome rate in the intervention group (25% enhancement) The α value was chosen at the level of statistical significance with 95% confidence (α=0.05) and the β ) value was equal to 10.5 By value was equal to 0.2 Hence, the ( substituting the above values into the formula, the n value was obtained to be equal to 73.5 The official sample size of this study (n) was 76 patients 2.2.3 Sampling process Subjects were patients with mild and moderate periodontitis/Type DM according to diagnostic criteria of CDC and AAP (2015) Patients were randomly divided into groups by drawing even or odd numbers 2.2.4 Materials and equipments 2.2.4.1 Examination material - Research form - Examination tools: periodontal probes (Apex dental USA), - Digital X-ray Imaging 2.2.4.2 Blood testing equipment - Inflammatory Factor Analyzer (Bio-Plex 200): testing for inflammatory cytokines such as TNF-α, IL-1β, IL-6 - CRP Au 5800 Instrument: for CRP test - Premier Hb 9210: for HbA1c test 2.2.4.3 Periodontal treatment tools - Ultrasonic scaler (Bobcat) - Manual instruments: Gracey (Hu-friedy) - Diode laser: AMD LASERS Picasso (USA) 2.2.5 Research criteria and evaluation methods 2.2.5.1 General features - Gender: male or female - Age: divided into groups under 60, above 60 years old - Duration of diabetes: divided into groups: under years, from to 10 years and over 10 years 2.2.5.2 Diagnosing and monitoring diabetes status Patients were diagnosed with diabetes according to ADA (2015): HbA1c more than 6.5% HbA1c testing before treatment, after 3-month and 6-month treatment 2.2.5.3 Clinical features and Diagnosing periodontitis levels and Periodontal Index examination: Plaque Index (PlI) Gingival Index (GI) Periodontal Pocket Depth (PD) Clinical Attachment Loss (CAL) Bleeding on Probing (BOP) According to CDC and AAP (2015): - Mild periodontitis: ≥ sites (different tooth), PD ≥ 4mm or ≥ sites (different tooth), CAL ≥ 3mm - Moderate periodontitis: ≥ sites (different tooth) 5mm≤ PD < 7mm or ≥ sites (different tooth), CAL ≥ 4mm 2.2.5.3 Inflammatory immune factors Quantitative test of CRP, TNF-α, IL-1β, IL-6 levels in the blood before treatment, after 1-month and 6-month after treatment Quantification of serum TNF-α, IL-1β, IL-6 by multiplex bead technique, using Magnetic Luminex Assay multiplex kit of Bioplex company (USA) at Laboratory of Pathophysiology-Immunology, Hue University of Medicine and Pharmacy 2.2.6 Research progress 2.2.6.1 Before treatment Patients were asked about the disease, clinically examined, performed X-ray imaging of the tooth root (digital) for teeth with periodontal pockets, taken blood samples, and written medical records 2.2.6.2 Periodontitis treatment progress - Oral hygiene instruction - Scaling and root planning Step 1: Antiseptic cleaning for the mouth area Step 2: Scaling and root planning (SRP) Step 3: Adjunctive treatment Intervention group (SRP+DL): 810nm diode laser application for teeth Teeth with periodontal pockets: Place the fiber tip close to the bottom, activate the laser light for 10 seconds Teeth with gingivitis: Place the fiber tip in the gingival crevice, activate the laser light for seconds Control group (SRP): saline irrigation Diode Laser 810nm irradiation process Diode laser procedure supported periodontitis treatment based on the research by Kocak (2016) Single-dose diode laser-assisted irradiation for teeth with periodontal pockets and gingivitis immediately after SRP Mode setting: 1.5 W power, pulse interval (frequency 20Hz, pulse width 20ms), 15J/cm2 of energy Doctors, assistants, patients wore protected glasses The optic fiber was inserted into the periodontal pocket base or gingival crevice, direction of the fiber tip toward the soft wall (gingival tissue) The device was activated and fiber was move slowly from apical to coronal and vertical direction on the outer and inner surfaces The irradiation time is 10 seconds and seconds for periodontal pockets and for gingivitis, respectively Saline irrigation 2.2.6.2 After treatment Periodontal index were examined (PlI, GI, BOP, PD, CAL) after 1-month, 3-month and 6-month treatment HbA1c was tested after 3-month and 6-month treatment 11 Chapter RESULTS 3.1 CLINICAL FEATURES, BIOCHEMICAL INDICATORS, INFLAMMATORY IMMUNE FACTORS IN PERIODONTITIS PATIENTS WITH TYPE DIABETES 3.1.1 Clinical features The average age was 63.9 years old The average age of the two groups was not statistically significant (p>0.05) Male proportion accounted for 34.2%, female accounted for 65.8% The male to female ratio of the two groups was not statistically significant (p>0.05) The average duration of diabetes was 9.12 years The average duration of diabetes in the two groups was not statistically significant (p>0.05) The average number of teeth remaining was 21.6 teeth The patients brushed their teeth once per day, accounting for 60.5%, and brushed their teeth 2-3 times per day accounted for 39.9% Accompanied disease with DM was hypertension 3.1.1.3 Periodontal indices in two study groups Table 3.6 Comparison of periodontal indices in two groups Group SRP+DL SRP Total (M ± SD) (M ± SD) (M ± SD) PlI 1.22 ± 0.45 1.20 ± 0.43 1.21 ± 0.44 0.81 GI 1.51 ± 0.34 1.41 ± 0.34 1.46 ± 0.34 0.21 BOP (%) 27.73 ± 11.97 24.67 ± 7.17 26.20 ± 9.92 0.18 PD (mm) 1.97 ± 0.28 1.95 ± 0.28 1.96 ± 0.28 0.76 CAL (mm) 2.35 ± 0.37 2.34 ± 0.37 2.34 ± 0.36 0.96 Index P 12 Remarks: The average periodontal indices were PlI=1.21; GI=1.46; BOP=26.2%; PD=1.96mm; CAL=2.34mm The mean periodontal indices between the two groups was not statistically significant (p>0.05) Moderate and mild periodontitis accounted for 80.3%, and 19.7%, respectively The severity of periodontitis between the two groups was not statistically significant, (p>0.05) 3.1.2 Biochemical indicators in two study groups Table 3.7 HbA1c before treatment in two study groups Group SRP+DL Index (M ± SD) HbA1c (%) 8.17 ± 1.19 SRP Total (M ± SD) (M ± SD) 8.19 ± 1.57 8.18 ± 1.38 p 0.73 Remarks: The mean HbA1c was 8.18% The mean HbA1c between the two study groups was not statistically significant (p>0.05) 3.1.3 Inflammatory immune factors in two study groups Table 3.8 Comparison of CRP, TNF-α, IL-1β, IL-6 levels in two groups Group SRP+DL Index (M ± SD) SRP (M ± SD) Total (M ± SD) p CRP (mg/L) 2.26 ± 2.66 2.40 ± 2.91 2.33 ± 2.76 0.381 TNF-α (ng/mL) 3.88 ± 4.76 3.78 ± 2.24 3.83 ± 3.67
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