Effects Of Periodontal Treatment On Periodontitis Control And Metabolic Level In Patients With Type 2 Diabetes

Chronic periodontitis and diabetes mellitus appear to totally different diseases, for the former is a localized periodontal infection due to oral bacteria, while the latter is regarded as systemic metabolic disorder. Recently, cross-susceptibility between periodontitis and diabetes reveals complex internal relationships between them. They share mutual genetic backgrounds and clinical risk factors, such as smoking, age, coronary heart disease, high pressure and dysfunction of white blood cells. And both can upgrade systemic immune response and cause excessive inflammatory mediators.While world-wide evidence tends to prove that diabetes adversely affects periodontal health, there is insufficient clue whether periodontitis may aggravate metabolic control and systemic inflammation. Regarding the effects of periodontal infection on glycemic control of diabetes, more direct, empirical evidence comes from treatment studies, compared to other research means such as cross-sectional survey, longitudinal observation study and animal experiments. However, currently there is no consensus as to whether non-surgical periodontal therapy may improve glycemic control.In review of literature, it is not difficult to recognize great heterogeneity and deficiencies in designs of treatment intervention studies. These include limited subjects enrolled in most of researches, difference in observation period and follow-up intervals, different inclusion criteria and lack of unified standards for grouping and setting controls, interference of systemic intake of antibiotics. Therefore prospective, randomized and well controlled periodontal intervention studies are warranted to investigate the contribution of periodontal infection to the metabolic level and systemic inflammatory status of subjects with type 2 diabetes.This research project, including a cross-sectional survey and a longitudinal randomized treatment intervention study, aims to explore the relationship of periodontitis with diabetes and clarify effects of periodontal treatment on periodontitis control, metabolic level and systemic inflammatory status in patients with type 2 diabetes.Main contents of this research project are:ⅰto set up detailed database of inquiry questionnaire, clinical information and biological samples for Chinese patients with type 2 diabetes;ⅱto explore the relationship of periodontal parameters with metabolic level as well as systemic inflammatory markers in patients with type 2 diabetes;ⅲto evaluate effects of periodontal treatment on metabolic level and periodontal inflammatory control in patients with type 2 diabetes;ⅳto clarify changes of circulating inflammatory markers before and after periodontal therapy in patients with type 2 diabetes.1. Association of periodontal parameters with metabolic level, systemic inflammatory markers in patients with type 2 diabetes (cross-sectional study)From September 2008 to May 2009, patients attending diabetes-oriented educational classes at 5 diabetes centers in Guangzhou City, China, were invited to participate in this study. A total of 140 interested patients accepted invitations, who were aged 36-85 years (76 males and 64 females). All subjects were diagnosed with type 2 diabetes according to WHO criteria at least 6 months before the investigation. All of them had at least fourteen natural teeth remained and were free of known major medical complications such as coronary heart disease. For entry to this study, patients were also required a diagnosis of chronic periodontitis according to the criteria of the American Academy of Periodontology. Exclusion criteria were:(ⅰ)presence of an active infection other than periodontitis; (ⅱ) intake of antibiotics in the previous 4 weeks; (ⅲ)pregnancy or lactation; (ⅳ) periodontal treatment within the last six months; (ⅴ)treatment with any medication known to affect the serum inflammatory markers.Periodontal examinations including full-mouth assessment of plaque index (PLI), probing depths (PD), bleeding on probing (BOP), gingival recession (GR) and clinical attachment level (AL) were applied. Blood analyses were carried out for glycated haemoglobin (HbA1c), fasting glucose (FPG), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-a) and lipid profiles (including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)). Then subjects were divided into 3 groups according to tertiles of mean PD and compared.Upon an analysis of covariance, subjects with increased mean PD had significantly higher HbA1c and hsCRP (P<0.05). No significant difference was found among different groups in serum TNF-α, fasting glucose and lipid profiles levels (P>0.05). In correlation analysis, HbA1c (r=0.2272, P=0.009) and hsCRP (r=0.2336, P=0.007) was associated with mean PD, but not with mean AL, mean GR, PLI, or BOP (P>0.05), after controlling for age, gender, BMI, duration of diabetes mellitus, smoking, regular physical exercise, and alcohol drinking. Other parameters (FPG, TNF-α, TC, HDL-C, LDL-C and TG) did not show positive correlation with mean PD. After adjustment for possible confounders, the mean PD emerged as a significant predictor variable for elevated HbA1c and hsCRP (P<0.05). Chronic periodontitis is associated with glycemic metabolic and serum hsCRP levels, but not lipid profiles or TNF-a level, in patients with type 2 diabetes.2. Effects of non-surgical periodontal treatment on clinical and immunological response and metabolic control in patients with type 2 diabetesFrom September 2008 to September 2009, a total of 134 patients participating previous cross-sectional study were recruited in this longitudinal study. Inclusion criteria were:(1) patients diagnosed with type 2 diabetes mellitus for more than 1 year and in stabilized condition; (2) no modification for diabetes treatment in the past 2 months; (3) free of major diabetic complications such as coronary heart disease; (4) presence of≥16 teeth in the mouth. Additional exclusion criteria were applied:(1) presence of an active infection other than periodontitis; (2) intake of antibiotics in the previous 3 months; (3) pregnancy or lactation; (4) periodontal treatment within the last 12 months; (5)treatment with any medication known to affect the serum inflammatory markers; (6) refusal of informed consent. According to random number table, all subjects were randomly divided into 3 groups:treatment groupⅠ(group 1), treatment groupⅡ(group 2) and control group.Group 1 received non-surgical periodontal treatment at baseline and additional periodontal intervention (subgingival curettage) at 3 month follow-up visit. Group 2 received non-surgical periodontal treatment at baseline and only preventive supragingival scaling at 3 month follow-up. Control group did not receive any treatment until the end of study. Non-surgical treatment included oral hygiene instruction (OHI), supragingival scaling, subgingival curettage, root planning, occlusal adjustment and extraction of hopeless tooth. The therapeutic phase was completed within 24 hours by an experienced periodontist at baseline visit. Patients were then re-examined at 1.5,3 and 6 months after completion of the treatment. At each visit, blood samples were taken to evaluate metabolic level (FPG, HbA1c, TC, HDL-C, LDL-C and TG) and immunologic change (including TNF-a and hsCRP), clinical periodontal assessment (including PLI, PD,%PD≤3mm,%PD 4-5mm, %PD≥6mm, GR, Al and BOP) were performed, oral hygiene instructions were reinforced. Subjects were instructed to continue with their medical treatment of diabetes mellitus, diet and lifestyle without modifications and no application of antibiotics during the whole study period.When homogeneity of the study groups for baseline information achieved, a two-way ANOVA (group factor:group 1, group 2 and control group; time factor: initial visit,1.5,3,6 months) with repeated measures on the time factor was used to analyze these clinical, immunological and metabolic variables.8 patients withdrew from the research project with the dropout rate 5.97%, and the rest 126 patients (group 1, N=42; group 2, N=43; control group, N=41) completed the study.The present study showed, mean PD,%PD 4-5mm,%PD≥6mm, PLI, BOP and mean AL in group 1 and group 2 significantly reduced, while%PD≤3mm significantly increased after initial periodontal treatment. There was no significant difference between group1 and group 2. All clinical parameters, except for PLI, BOP, in control group did not show significant change during the whole study period.Although HbA1c and FPG in group 1 and group 2 had a trend to reduce after baseline visit (P＜0.05), the three groups did not differ in HbA1c and FPG at any examination time (P>0.05).hsCRP in group 1 and group 2 significantly reduced after treatment (P<0.05), while fluctuation of hsCRP in control group did not show significance. At 6 months, group 1 and group 2 had a significant lower hsCRP level in comparison with control group, with no difference in group 1 and group 2.TG, TC, HDL-C and LDL-C in three groups had a trend to reduce during the whole study period and there was no difference among the three groups.Fluctuation of TNF-a level in three groups did not show significance after treatment and there was no difference among the three groups.Selected 39 patients with moderate to severe periodontitis (defined as mean PD >2.5mm, more than 20% sites with probing depth≥4mm in this study) from the enrolled 126 subjects and analyzed. As the previous outcome found no significant difference between group 1 and group 2, the following analysis combined the two groups into a new treatment group (N=30) in comparison with control group (N=9).HbA1c in treatment group had a trend to decrease, while HbA1c in control group had a trend to increase during the study period. However, no significant difference was found between the two groups. hsCRP in treatment group significant reduced after initial periodontal intervention, and there was significant difference between treatment group and control group.According to outcomes of this longitudinal clinical study, we can draw the following conclusions:Combining change of all periodontal parameters (including PLI, mean PD, %PD≤3mm,%PD 4-5mm,%PD≥6mm, BOP and mean AL) during the study period, we can believe non-surgical periodontal treatment can effective control periodontal inflammation in patients with type 2 diabetes. The best therapeutic effect will be obtained 6 months after initial periodontal treatment, and any other periodontal intervention measures within this period can not bring better outcome.Evidence is not enough to support non-surgical periodontal treatment can improve glycemic control in patients with type 2 diabetes. But trends in some results are in favor of periodontal treatment.Gradual decrease of hsCRP after control of periodontal inflammation shows non-surgical periodontal treatment can effective reduce serum hsCRP level in patients with type 2 diabetes.Non-surgical periodontal therapy has little impact on lipid metabolic control in patients with type 2 diabetes patients.Non-surgical periodontal treatment can hardly reduce serum TNF-a level in patients with type 2 diabetes patients.