overall OR for patients with diabetes among those with periodontitis was 2.27, compared to those without periodontitis. However, there was a substantial variability in the definitions of periodontitis, a combination of self-reported and clinically assessed diabetes, and a lack of assessment of confounding for diabetes in the included studies, introducing estimation bias80.
Nevertheless, according to Graziani et al2, periodontitis has an impact on diabetes control, including its incidence and complications. Poor glycaemic control and a higher risk of developing diabetes are observed in systemically healthy individuals with periodontitis. Diabetic individuals with periodontitis demonstrate a worsening of glycaemic control and significantly higher prevalence of diabetes-related complications. For example, patients with T2DM and comorbid periodontitis have significantly more cardiorenal complications (OR 3.5, 95% CI 1.2 to 10.0)81, neuropathic foot ulcerations (OR 6.6, 95% CI 2.3 to 18.8)82, cardiovascular complications (OR 2.6, 95% CI 1.6 to 4.2)83 and overall mortality (RR 1.51, 95% CI 1.11 to 2.04 for each 20% increment in mean whole-mouth alveolar bone loss)84. However, the studies suffered from intrinsic limitations that render the overall applicability of the results weak. For example, some of the evidence was indirectly drawn from manuscripts that did not have the primary intention of assessing the effect of periodontitis on glycaemic control. In addition, there is heterogeneity in terms of adjustment of confounders as well as of the definitions of periodontitis. Furthermore, the possibilities of selective data reporting and publication bias cannot be excluded2.
Taken together, there is strong and significant evidence that DM has an impact on the prevalence and severity of periodontitis. This evidence has evolved from surveys, case-control studies, narrative reviews and systematic reviews, but mainly from epidemiological studies. The association appears to be similar in T1DM and T2DM; however, the available evidence is focused particularly on T2DM. There is little evidence that the clinical features of periodontitis in patients with DM differ from those without DM. Regarding the impact of periodontitis on DM, there is accumulating evidence that periodontitis contributes to the onset and persistence of hyperglycaemia, poorer glycaemic control in individuals with DM, and an increase in DM incidence85,86.
Interventional studies
Consequently, if periodontitis has a role in diabetes, it would be logical to infer that periodontal therapy impacts circulating levels of inflammatory cytokines, adiponectin, insulin resistance and glycaemic control. Efforts have been made to understand the impact of periodontal therapy in diabetes control. It has been shown that periodontal treatment can improve glycaemic control, lipid profile and insulin resistance, reduce serum inflammatory cytokine levels and increase serum adiponectin levels in T2DM patients87. Sun et al87 studied 190 moderately to poorly controlled T2DM patients (HbA1c between 7.5% and 9.5%) with periodontitis. They observed that after 3 months of periodontal therapy, the serum levels of C-reactive protein, TNF-α, interleukin (IL)-6, fasting plasma glucose, HbA1c, fasting insulin and the HOMA-IR index decreased, the latter being a method for assessing insulin resistance from fasting blood glucose and insulin concentrations. Adiponectin was significantly increased in the treated group compared to the non-treated group87.
The positive impact of a non-surgical periodontal therapy on HbA1c was also observed in a recent study by D’Aiuto et al88. In this 12-month randomised clinical trial, 264 subjects were allocated to receive intensive periodontal treatment (IPT; whole mouth subgingival scaling, surgical periodontal therapy and supportive periodontal therapy every 3 months until completion of the study) or control periodontal treatment (CPT; supragingival scaling and polishing at the same time-points as in the IPT group). They observed that HbA1c was 0.6% (95% CI 0.3% to 0.9%) lower in the IPT group than in the CPT group after 12 months, with adjustment for baseline HbA1c, age, sex, ethnicity, smoking status, duration of diabetes and BMI88. The question that still remains is whether the observed benefits are sustained beyond 12 months.
The impact of periodontal treatment is largely witnessed by the systematic reviews on this topic. Engebretson and Kocher89 demonstrated in a meta-analysis that periodontal therapy significantly reduced HbA1c 3 to 4 months post-treatment, ranging from 0.27% to 1.03% (95% CI −0.54 to −0.19). In the latest update, Madianos and Koromantzos90 confirmed that non-surgical periodontal therapy reduced HbA1c in patients with diabetes. They observed that there was a reduction 3 to 4 months post-treatment, ranging from −0.27% (95% CI −0.46 to −0.07) to −1.03% (95% CI 0.36 to −1.70) and at 6 months post-treatment, the HbA1c reduction ranged from −0.02 (95% CI −0.20 to −0.16) to −1.18% (95% CI −0.72 to −1.64). The data derived from the meta-analysis clearly indicate the positive effect of periodontal decontamination on glycaemic control. It is important to highlight that this effect cannot be underestimated since, as shown before, for every percentage point decrease in HbA1c, there is a 35% reduction in the risk of microvascular complications, 25% reduction in diabetes-related deaths, a 7% reduction in all-cause mortality, and an 18% reduction in combined fatal and nonfatal myocardial infarction. This further reinforces the hypothesis of a link between periodontitis and diabetes90.
Conversely, in a multicentre, randomised clinical trial, Engebretson et al91 observed that non-surgical periodontal therapy did not improve glycaemic control in patients with T2DM. However, several authors indicate that the periodontal therapy provided in this study failed to clinically manage the periodontal infection, since the subjects still had high residual plaque levels (72%) and bleeding scores (42%) after the therapy. In addition, the mean HbA1c value at baseline was close to the therapeutic target, thus, a substantial improvement of the HbA1c by periodontal intervention could not be expected. Lastly, the subjects from the treatment group were obese (mean BMI 34.7), which would probably have masked any anti-inflammatory effect of successful periodontal treatment92.
The controversy regarding the effect of periodontal treatment on glycaemic control may be related to the heterogeneity of the trial designs. These are, for example, non-surgical vs. surgical periodontal therapy provided, the periodontal treatment outcomes assessed, the periodontitis definition used (severity vs. extent vs. both), the selection criteria for the type of DM (T1DM vs. T2DM vs. both), the variability in the range of levels of glycated haemoglobin, and the follow-up periods, where periods of 3 months to assess HbA1c changes may be considered too short23,86. Table 1-4 lists the most important interventional studies. It presents the effect of periodontal treatment on glycaemic control of T1DM and T2DM. Table 1-5 gives an overview of clinical studies investigating the association between periodontitis and T1DM.
Table 1-4 Interventional studies assessing the effect of periodontal