Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial

BACKGROUND: Chronic inflammation is believed to be a major mechanism underlying the pathophysiology of type 2 diabetes. Periodontitis is a cause of systemic inflammation. We aimed to assess the effects of periodontal treatment on glycaemic control in people with type 2 diabetes. METHODS: In this 12 month, single-centre, parallel-group, investigator-masked, randomised trial, we recruited patients with type 2 diabetes, moderate-to-severe periodontitis, and at least 15 teeth from four local hospitals and 15 medical or dental practices in the UK. We randomly assigned patients (1:1) using a computer-generated table to receive intensive periodontal treatment (IPT; whole mouth subgingival scaling, surgical periodontal therapy [if the participants showed good oral hygiene practice; otherwise dental cleaning again], and supportive periodontal therapy every 3 months until completion of the study) or control periodontal treatment (CPT; supra-gingival scaling and polishing at the same timepoints as in the IPT group). Treatment allocation included a process of minimisation in terms of diabetes onset, smoking status, sex, and periodontitis severity. Allocation to treatment was concealed in an opaque envelope and revealed to the clinician on the day of first treatment. With the exception of dental staff who performed the treatment and clinical examinations, all study investigators were masked to group allocation. The primary outcome was between-group difference in HbA1c at 12 months in the intention-to-treat population. This study is registered with the ISRCTN registry, number ISRCTN83229304. FINDINGS: Between Oct 1, 2008, and Oct 31, 2012, we randomly assigned 264 patients to IPT (n=133) or CPT (n=131), all of whom were included in the intention-to-treat population. At baseline, mean HbA1c was 8·1% (SD 1·7) in both groups. After 12 months, unadjusted mean HbA1c was 8·3% (SE 0·2) in the CPT group and 7·8% (0·2) in the IPT group; with adjustment for baseline HbA1c, age, sex, ethnicity, smoking status, duration of diabetes, and BMI, HbA1c was 0·6% (95% CI 0·3-0·9; p<0·0001) lower in the IPT group than in the CPT group. At least one adverse event was reported in 30 (23%) of 133 patients in the IPT group and 23 (18%) of 131 patients in the CPT group. Serious adverse events were reported in 11 (8%) patients in the IPT group, including one (1%) death, and 11 (8%) patients in the CPT group, including three (2%) deaths. INTERPRETATION: Compared with CPT, IPT reduced HbA1c in patients with type 2 diabetes and moderate-to-severe periodontitis after 12 months. These results suggest that routine oral health assessment and treatment of periodontitis could be important for effective management of type 2 diabetes. FUNDING: Diabetes UK and UK National Institute for Health Research.Diabetes UK and UK National Institute for Health Researc

Guided tissue regeneration for periodontal infra-bony defects (Cochrane Review)

BACKGROUND: Conventional treatment of destructive periodontal (gum) disease arrests the disease but does not usually regain the bone support or connective tissue lost in the disease process. Guided tissue regeneration (GTR) is a surgical procedure that specifically aims to regenerate the periodontal tissues when the disease is advanced and could overcome some of the limitations of conventional therapy. OBJECTIVES: To assess the efficacy of GTR in the treatment of periodontal infra-bony defects measured against conventional surgery (open flap debridement (OFD)) and factors affecting outcomes. SEARCH STRATEGY: We conducted an electronic search of the Cochrane Oral Health Group Trials Register, MEDLINE and EMBASE up to April 2004. Handsearching included Journal of Periodontology, Journal of Clinical Periodontology, Journal of Periodontal Research and bibliographies of all relevant papers and review articles up to April 2004. In addition, we contacted experts/groups/companies involved in surgical research to find other trials or unpublished material or to clarify ambiguous or missing data and posted requests for data on two periodontal electronic discussion groups. SELECTION CRITERIA: Randomised, controlled trials (RCTs) of at least 12 months duration comparing guided tissue regeneration (with or without graft materials) with open flap debridement for the treatment of periodontal infra-bony defects. Furcation involvements and studies specifically treating aggressive periodontitis were excluded. DATA COLLECTION AND ANALYSIS: Screening of possible studies and data extraction was conducted independently. The methodological quality of studies was assessed in duplicate using individual components and agreement determined by Kappa scores. Methodological quality was used in sensitivity analyses to test the robustness of the conclusions. The Cochrane Oral Health Group statistical guidelines were followed and the results expressed as mean differences (MD and 95% CI) for continuous outcomes and risk ratios (RR and 95% CI) for dichotomous outcomes calculated using random-effects models. Any heterogeneity was investigated. The primary outcome measure was change in clinical attachment. MAIN RESULTS: The search produced 626 titles, of these 596 were clearly not relevant to the review. The full text of 32 studies of possible relevance was obtained and 15 studies were excluded. Therefore 17 RCTs were included in this review, 16 studies testing GTR alone and two testing GTR+bone substitutes (one study had both test treatment arms).No tooth loss was reported in any study although these data are incomplete where patient follow up was not complete. For attachment level change, the mean difference between GTR and OFD was 1.22 mm (95% CI Random Effects: 0.80 to 1.64, chi squared for heterogeneity 69.1 (df = 15), P < 0.001, I(2) = 78%) and for GTR + bone substitutes was 1.25 mm (95% CI 0.89 to 1.61, chi squared for heterogeneity 0.01 (df = 1), P = 0.91). GTR showed a significant benefit when comparing the numbers of sites failing to gain 2 mm attachment with risk ratio 0.54 (95% CI Random Effects: 0.31 to 0.96, chi squared for heterogeneity 8.9 (df = 5), P = 0.11). The number needed to treat (NNT) for GTR to achieve one extra site gaining 2 mm or more attachment over open flap debridement was therefore 8 (95% CI 5 to 33), based on an incidence of 28% of sites in the control group failing to gain 2 mm or more of attachment. For baseline incidences in the range of the control groups of 3% and 55% the NNTs are 71 and 4. Probing depth reduction was greater for GTR than OFD: 1.21 mm (95% CI 0.53 to 1.88, chi squared for heterogeneity 62.9 (df = 10), P < 0.001, I(2) = 84%) or GTR + bone substitutes, weighted mean difference 1.24 mm (95% CI 0.89 to 1.59, chi squared for heterogeneity 0.03 (df = 1), P = 0.85). For gingival recession, a statistically significant difference between GTR and open flap debridement controls was evident (mean difference 0.26 mm (95% CI Random Effects: 0.08, 0.43, chi squared for heterogeneity 2.7 (df = 8), P = 0.95), with a greater change in recession from baseline for the control group. Regarding hard tissue probing at surgical re-entry, a statistically significant greater gain was found for GTR compared with open flap debridement. This amounted to a weighted mean difference of 1.39 mm (95% CI 1.08 to 1.71, chi squared for heterogeneity 0.85 (df = 2), P = 0.65). For GTR + bone substitutes the difference was greater, with mean difference 3.37 mm (95% CI 3.14 to 3.61). Adverse effects were generally minor although with an increased treatment time for GTR. Exposure of the barrier membrane was frequently reported with a lack of evidence of an effect on healing. AUTHORS' CONCLUSIONS: GTR has a greater effect on probing measures of periodontal treatment than open flap debridement, including improved attachment gain, reduced pocket depth, less increase in gingival recession and more gain in hard tissue probing at re-entry surgery. However there is marked variability between studies and the clinical relevance of these changes is unknown. As a result, it is difficult to draw general conclusions about the clinical benefit of GTR. Whilst there is evidence that GTR can demonstrate a significant improvement over conventional open flap surgery, the factors affecting outcomes are unclear from the literature and these might include study conduct issues such as bias. Therefore, patients and health professionals need to consider the predictability of the technique compared with other methods of treatment before making final decisions on use. Since trial reports were often incomplete, we recommend that future trials should follow the CONSORT statement both in their conduct and reporting. There is therefore little value in future research repeating simple, small efficacy studies. The priority should be to identify factors associated with improved outcomes as well as investigating outcomes relevant to patients. Types of research might include large observational studies to generate hypotheses for testing in clinical trials, qualitative studies on patient-centred outcomes and trials exploring innovative analytic methods such as multilevel modelling. Open flap surgery should remain the control comparison in these studies