Effects of nonsurgical periodontal treatment on glycated haemoglobin on type 2 diabetes patients (PARODIA 1 study): a randomized controlled trial in a sub-Saharan Africa population

African and particularly sub-Saharan Africa is faced with a significant and increasing burden of type 2 diabetes (T2D) with high prevalence in urban population, in addition of having the largest proportion of undiagnosed patients in the world. This makes it one of the most vulnerable regions for this condition worldwide now and in coming decades [1‐3]. The situation is worsened by the fact that majority of patients with diabetes in sub-Saharan Africa are not well controlled with less than 30% reaching recommended glycaemic targets [4]. Poor glycaemic control favours incidence and severity of acute and chronic infections such as oral microorganism attacks. Periodontitis is the commonest oral disease affecting population worldwide with greater prevalence, severity and extent in diabetes patients [5‐8]. In the other hand, severe periodontitis may exacerbate diabetes-induced hyperglycaemia [9‐12] suggesting a bidirectional relationship between periodontal disease and diabetes in relation with inflammation and insulin resistance [13‐18]. Despite growing evidence on the benefit of periodontal treatment on glycaemic control in people living with diabetes [19‐25], randomized controlled trial-derived evidence is lacking from Africa, the continent with the largest burden of infectious diseases and uncontrolled diabetes. Therefore, we carried out this study to assess the effects of non-surgical periodontal treatment on glycated haemoglobin in a sub-Saharan Africa type 2 diabetes populations.

We recruited 34 participants from a sample of 70 poorly controlled type 2 diabetes patients. Twenty five were ineligible because of the absence of periodontitis, three of them refused to participate, three were smokers, and five had a history of antibiotics intake or scaling less than three months ago. This left 34 eligible for randomization, as they gave their consent they were all randomized. Four participants were excluded after randomization (Fig. 1). There was no difference in the number of exclusion by study group (two in the treatment group and two in the control group).

After a twelve weeks follow-up of non-surgical treatment of chronic periodontitis by full-mouth ultrasonic scaling and root planning associated with sub gingival irrigation with 10% povidone iodine solution, we obtained a significant improvement of glycaemic control translated by a reduction of HbA1c levels to 30.9% of the baseline. The mean changes in HbA1c were found to be significantly different between the two groups. This permitted to conclude about the effect attributable to periodontal treatment which is a reduction of HbA1c of 2.2 points. Improvement of periodontal health characterised by an attachment gain of 1.3 mm with the reduction of plaque index and gingival bleeding index participates in reducing inflammation and consequently peripheral insulin resistance, as well as glycaemic level and glycated haemoglobin.

These results support those of previous studies which showed that elimination of periodontal infection can improve glycaemic control [19, 20, 30]. Loos 2005 [16] suggested that periodontal infection determine a low grade inflammation characterised by an up-regulation of pro-inflammatory cytokines like tumour necrosis factor-α (TNFα), interleukin-1 (IL-1) and IL-6 which is responsible of insulin resistance and poor glycaemic control [13, 14]. This means that periodontal treatment can improve glycaemic control in poorly controlled diabetes patients through the reduction of pro-inflammatory cytokines blood levels. These evidences come from many authors including Sun et al. [24], who showed that surgical and non-surgical periodontal therapy combined with systemic antibiotics intake improved glycaemic control, reduced serum inflammatory cytokines levels and insulin resistance in moderately poorly controlled T2D patients [24, 31‐33].

However the mean change in HbA1c seems to be larger than the one found in similar studies in diabetic patients from other regions and especially in developed countries [19‐21, 30, 34]. This can be related to study population and periodontal therapy used. Some of the previous studies included smokers even if it is well known that nicotin contained in cigarette is responsible of delayed periodontal healing [35, 36]. On the other hand, patients treated by insulin were excluded. If periodontal treatment can improve insulin sensibility as showed by Iwamoto et al. [37], this can increase the effect of insulin therapy and thereby rapidly decreasing HbA1c levels [24].

One of the advantages of our study was the use of a subgingival irrigation which improves periodontal health in a better way when it is adjunct to periodontal treatment compared to periodontal treatment alone [38]. The effects of irrigation are more important if the irrigant is an antiseptic solution like the 10% povidone iodine solution used in this study [39]. Povidone iodine is a highly efficient microbicide by contact for gram-positive and gram-negative bacteria, fungi, mycobacteria, viruses and protozoans. Because of rapid microbial killing, a short term application of this agent alone may produce an adequate antimicrobial effect. In addition, povidone iodine is exempt of blood or saliva proteins deactivation and emergence of povidone iodine resistance micro-organism has not been reported to have been detected to date.

Since a significant drop in glycated haemoglobin of about 1 point is associated with a decrease of the risk of complications by 35%, a 25% reduction in diabetes-related deaths and a 18% reduction in combined fatal and non-fatal myocardial infarction [40], we can further evaluate and appreciate the benefit presented by the treatment of periodontitis in diabetic patients in our context [41]. This non-surgical periodontal treatment helps to reduce glycated haemoglobin by more than 2 points. Its use can therefore reduce cardiovascular and renal mortality related to diabetes as suggested by Saremi et al. in preceding decade [42]. This highlights the urgency of a greater sensitization on the importance of the treatment of chronic periodontitis in patients with diabetes and the necessity for physicians and other hospital practitioners to be awareness of this relationship and to integrate periodontal consultations in the monitoring and the overall management of the diabetic patient. It is imperative for physicians to consider periodontal structures as potential infection site as well as skin, urinary tract and lungs and to systematically check the presence of a periodontal infection.

In addition to the clinical benefit such practice also offers the advantage of a reduction of the cost of treatment for allowing a reduction of more than 1% of glycated hemoglobin, it is better than all oral anti-diabetic treatment currently available on the market of low developing country. Non-surgical treatment of chronic periodontitis in diabetic patients would therefore reduce the cost of treatment and would be a good alternative before applying second-line combination therapy for poorly controlled patients previously on monotherapy. Moreover, with no side effects, it has the advantage of a good tolerance and greater safety than oral anti diabetic drugs which are well known to have at least a notorious side effect.

Diabetes and periodontitis have some risk factors in common like obesity. In our population the mean of BMI was about 28.2 ± 5.4 kg/m², obesity was found in 43.3% of the participants. It appears that those 3 states are linked by inflammation as demonstrated by Genco et al. [13] in their proposed model linking inflammation to obesity diabetes and periodontal infections. In this model, adipocytes secrete proinflammatory cytokines like TNF which is able to inhibit insulin signaling, leading to insulin resistance [13]. As time goes on, diabetes mellitus breaks out with another hyperinflammatory state and can be responsible of periodontitis infections onset. At the sight of these statements, we can think that the management of overweight or obesity can improve glycemic control in diabetic patients. More over the first lines for diabetic cares are non-pharmaceutical measures which include the diet. So, in this survey, the reduction of BMI could have contribute to glycemic control. However no significant drop in BMI values has been recorded after 3 months follow-up.

The patients included in this study had moderate to severe periodontitis according to CDC/AAP classification. However, as this case definition does not incorporate measurements from all the six sites, disease can be underestimate. In the CDC/AAP case definitions, the measurements of mid-bucal and mid –lingual are not includes, it means that furcation involvement is not assessed. Additionally, this case definition for periodontal status does not assess bleeding on probing so that informations about current inflammatory status are not incorporate. It means that this classification could not be suitable for a clinical trial but as we used complementary index like Ainamo and Bay index and evaluated changes in PPD and CAL means, the issues of our investigations are as attractive as expected.

As this study was design to evaluate the effects of periodontal treatment on glycated hemoglobin, we did not investigate the evolution of inflammation markers. Moreover, long term effects of the treatment were not determined. Meaning that the adoption of systematic screening and treatment or recommendations requires further studies at large-scale, randomized clinical trials, including measurements of inflammatory mediators to determine the relation between the reduction of HbA1c levels following periodontal therapy and inflammatory markers and longitudinal studies to determine long term effects of scaling and root planning associated to povidone iodine subgingival irrigation on glycaemic control.

The results of this single-blinded randomized and controlled clinical trial show that the addition of periodontal therapy including subgingival irrigation with a 10% povidone-iodine solution to current medical therapy improves glycaemic control in sub-Saharan African type 2 diabetes patients with poorly controlled diabetes.