Would Better Control of Diabetes Improve Oral/Periodontal (Gum) Health? A Short Narrative Review of how Dental Practitioners can contribute

Risk factors for Periodontal Disease, What are the implications?

Diabetes has indisputably been confirmed as one of the factors that increase the signs of periodontitis [2, 5, 7, 9, 14, 15, 16], with some studies suggesting up to a three-fold [1, 2] increase in risk. Other established risk factors for PD include cigarette smoking, stress and poor diet. Evidence illustrates that hyperglycaemia is biologically linked to periodontal tissue destruction by disturbing and altering the immuno- inflammatory response. These alterations are displayed by the production of local mediators such as cytokines (e.g interleukins) [2, 17] which highlights the clinical signs of the disease, particularly in Type II diabetes [18]. In a normal body homeostasis in relation to hyperglycaemia; glycosylation of proteins occurs frequently which result in the formation of advanced glycation end-products (AGE). The rate of AGE formation is markedly elevated in people with diabetes [2]. RAGE is a receptor for AGE, and the binding of these receptors advance the increase in the levels of inflammatory mediators (e.g IL-1B, TNF-α and IL-6) which can all promote the tissue change within the periodontium [17] and further periodontal tissue destruction [1, 2, 19]. Glycohemoglobin is formed continually in the human body, by the binding of haemoglobin and glucose [1]. This forms HbA1c. The level of circulating HbA1c in the body provides an estimate of an individual’s two-three months glycaemic control [8]. Thus, high levels reflect the increase of this inflammatory marker, leading to diabetic complications [1].

Another important source of cytokines is adipose tissue. Adipose tissue is abundant in obesity which is one of the manifestations of Type II diabetes. It is evident now, that adipose tissues play a role in the active endocrine secretion of cytokines, such as IL-6 and TNF-α13, and adipokines (e.g leptin and adiponectin). The levels of leptin are directly proportional to the number of adipose tissues; playing an important part in the inflammatory response, which in return correlates to the increased risk of developing Type II diabetes, and inevitably PD. Adiponectin, however, has an opposite effect to that of leptin; whereby, it is an anti- inflammatory. It is indirectly proportional to the number of adipose tissue present, therefore low numbers are associated with periodontal changes [2, 20, 21].

Longitudinal studies of the relationship between diabetes and Periodontal Disease started as long as forty years ago, by Cohen, et al. [22]. Recent to that, Seppälä, et al. [7], went to study the effect of Type I diabetes on PD over two years. It looked into subjects from three different departments of Medicine where they investigated a variety of dental examinations focused on the periodontium, comparing poor and well controlled glycaemic patients. Seppälä’s subjects were aged from 35-56 years [7]. Of the 50 subjects initially participating, only 22 completed the study. A very similar pattern of subjects leaving the experiment was shown in a cohort study, Cohen, et al. [22]. The reason for this study dropout rate was thought to be due to diabetic patients requiring urgent treatments as oppose to long term regular check-ups; observed by Thorstensson, et al. [23]. The only set back is the small number of participants. This reduces the validity of the study. However, the study did conclude that the incidence of Periodontitis was higher in poorly controlled diabetic individuals to that of controlled. These results were in conformity with previous studies [7]. Kaur, et al. looked into the association between Type I and Type II DM as to whether there is a risk of a deteriorating effect to the periodontal tissue health [15]. The research viewed the homogenous adult population in North Germany. The data was collected to examine if there was an increased prevalence to the extent of periodontal damage in those who had diabetes in comparison to those who are non-diabetics. Results were significant (Table 1) and the association of both diseases to PD were plausible. As this was a cross- sectional designed study, it lacked details that impacted on its conclusion; such as glucose intolerance tests, previous periodontal treatments, and previous glucose tests. More importantly, data on whether previous teeth were extracted due to worsening periodontal state was not noted, as the remaining dentition may not represent the long-term periodontal status. This particular study was distinctive, due to the high number of recruited participants; more than 4,000 individuals. Hideaki Hayashida, et al. [8] went to look further into the matter but in a different perspective. They examined the relationship of periodontitis and the levels of HbA1c in non-diabetic subjects. The study was also cross sectioned to small community-based residents, lacked the number of participants and mainly focused on elderly patients. It was concluded that periodontal characteristics were related to the high levels of HbA1c in non-diabetic individuals [8]. A large number of clinical research studies were undertaken to study the extent of diabetes mellitus as a risk factor for PD.

A number of meta-analyses were conducted to obtain a valid concensus of the relationship. Khaders, et al. [16] undertook a cross-sectional comparison study, comparing 18 literatures from 1970-2003 of the periodontal statuses in diabetics compared to non-diabetics. The use of a very strict inclusion criteria for the subjects in an attempt to qualify and quantify any significance was undertaken, and it was concluded that DM severely increases the extent of PD [16].

However, a smaller meta-analysis of ten interventional studies [24] assessing the impacts of periodontal treatment on diabetic control, found a non-significant reduction in HbA1c following the provision and intervention of periodontal treatment. It should be noted that this meta-analysis had a more lenient inclusion criteria, allowing for studies with smaller sample sizes. Furthermore, with studies focused on a Type I diabetic majority cohort, this can lead to further criticism of the outcomes. With Type I diabetic patients being more cautious of their glycaemic control of insulin to that of Type II patients [24], their HbA1c would be less likely to be significantly altered, thereby affecting the conclusion of the analysis. Khaders, et al. [16] utilising a stricter inclusion criteria, greater patient cohort (1,835 diabetic and 17,410 non-diabetic participants with ages ranged from 5 to 78 years) with a wider demographic (including patients from America, Argentina, England, Sweden, France, Turkey and Mauritius) improved the reliability and quality of the papers findings.

Evidence of How Dentists Can Improve Glycaemic Control

Periodontal treatment may be approached in either a surgical or non-surgical manner. Treatment aims at reduction in the subgingival oral biofilm in order to achieve homeostasis [25]. This can be achieved via debridement using scalers coupled with intensive oral hygiene instruction and patient motivation. Emerging evidence suggests that periodontal treatment in conjunction with systemic antibiotics may provide significantly improved outcomes for patients with severe periodontitis than non-surgical therapy alone [25, 26]. The effect of treating PD on diabetic patients is promising with a positive impact on glycaemic control [2]. Many studies tested this relationship in many perspectives. The meta-analyses of Janket, et al. [24] illustrated that after a periodontal intervention, HbA1c levels reduced by 0.38%. Other researchers went as far as providing systemic antibiotics (e.g doxycycline) to lower the inflammation markers such as C-Reactive Protein (CRP) and other immuno- inflammatory mediators. Those studies were criticised for a potential systemic bias as the antibiotics provided an external measure to accommodate the high levels of the inflammatory markers as oppose to dental intervention alone [24]. This type of arbitration would likely lead to over-estimation of the positive effect of the glycaemic control.

Normal interventions such as scaling and root debridement with subgingival irrigations were studied by Al-Mubarak [27]. The team looked into both types of DM in a randomised controlled trial. Measurements included systemic mediators (TNF-α and IL-1B) and HbA1c. Although the number of participants was small (52 subjects) it was conducted in a single diabetic centre, and showed significant results. It has proved that such interventions can play a positive value into periodontal health in diabetics [27]. However, the study overlooked if the subjects were smokers or not. Smoking has systemic implications which could manipulate the final results [28]. Commiso [9] undertook a study observing oral health and Type II diabetic glycaemic control. The study was small and unconvincing. Of the initial 118 patients that took part, only 9 patients went to be tested. Regardless of their significance in reduction of the HbA1c levels [9]; this is strongly criticised to show any significance due to the low number of participants that undertook the study, as they do not reflect a great spectrum of patient’s data. An Australian population was studied by Fitzsimmons, et al. [28]. The research looked at 939 subjects, 430 of whom had periodontitis, and sought to examine the link between local and systemic mediators (IL-1B and CRP) on the periodontal health. Their results proved significant, with a number of mediators also showing a significant association with a history of diabetes. The limitations to this study were their periodontal measurements; being inclusive to 3 sites instead of the normal 6, and their reliance on the subject’s declaration of medical and social history without confirming it from patient records [28]. Santos, et al. [29] had also shown that dental intervention could improve periodontal status with Type II diabetics. However, their results were based on a very short intervention time compared to a normal eight- week intervention. Hence a more longitudinal long-term data is required to reflect a true extent of periodontal association and glycaemic control [29].