Periodontal disease can increase the risk of developing diabetes or affect its control and treatment.


Periodontal disease can increase the risk of developing diabetes or affect its control and treatment.


Periodontitis and diabetes are chronic diseases of ever-growing worldwide prevalence. Ninety percent of the population is estimated to have some type of oral infectious disease, including caries and gingivitis, and up to 50% of all adults (60% of those over 65 years) are thought to have periodontitis. Meanwhile, the World Health Organization predicts that 439 million people will have diabetes in the year 2030 (currently estimated at 346 million).

Periodontitis is a chronic inflammatory disease initiated by a microbial infection, which triggers an innate immune response at first, and later, an acquired immune response, potentially causing major destruction to connective tissues and alveolar bone, and eventually tooth loss.

The onset of diabetes is preceded by an inflammatory process which leads to pancreatic beta-cell dysfunction and apoptosis, and favours the development of insulin resistance. It is therefore reasonable to acknowledge that comorbidities that cause an inflammatory immune system response are associated with an increase in risk for diabetes development or that they may affect its control and treatment, and therefore its morbidity and mortality.

Epidemiological studies have been performed relating a loss of dental attachment to an increase in HbA1c levels, so that each additional periodontal probing mm would correspond to a 0.13% increase in HbA1c levels. Patients with probing depths ≥6 mm would therefore have a 3.45 times greater risk of developing diabetes than those not suffering from periodontal disease.

Despite these data, evidence of the relationship between periodontal disease and glycaemic control is scarce, and studies representing the overall population are needed, as well as the use of a universal definition of periodontal disease. Nevertheless, it has been pointed out that patients with worse periodontal hygiene are at greater risk for poor glycaemic control and for experiencing diabetes-related complications, and even the development of diabetes in patients who do not already have it.

Pathogenic mechanisms

One of the main causes of diabetes and its associated complications is a poorly regulated immune system. Systemic cytokine alterations are key to the pathogenesis of Type 2 Diabetes Mellitus (DM2). These immunological changes can trigger insulin resistance and apoptosis in the islets of Langerhans (insulin-producing β-cells) leading to insulin deficiency.

Cytokine testing is therefore crucial in the pre-clinical diagnosis, development and treatment of diabetes.

The impact of diabetes on the pathogenesis of periodontitis and the impact of periodontitis on diabetes are hereby examined.

a) Impact of diabetes on the pathogenesis of periodontal disease

  • Microbial factors

There is no evidence in the currently available literature of the impact diabetes may have on periodontal microbiota, and so the presence of DM1 or DM2 and levels of glycaemic control do not seem to have significant influence on the composition of periodontal microbiota.

  • Cytokines and Adipokines

Diabetes can qualitatively and quantitatively alter the cytokine profiles of periodontitis patients.

The levels of proinflammatory cytokines such as IFN-gamma, IL-1B, IL-6 and PGE2, as well as chemokines such as MIP-2 and MCP-1 (macrophage inflammatory proteins) are higher in patients with diabetes and periodontitis compared to patients with a similar level of periodontitis not suffering from diabetes.

TNF-alpha may be associated with a prolongation of the immune response to biofilm in diabetic patients, promoting the development of periodontitis. However, there is not enough evidence regarding its role, as studies were conducted on animals, and no clinical trials were conducted.

Moreover, diabetes-induced hyperglycaemia can lead to dysregulation of immune responses through direct effects on immune cells. Levels of RANKL (nuclear factor-kappaB) and OPG (osteoprotegerin) can be modified in periodontitis patients with DM2, which is associated with poor glycaemic control, as are the levels of IL-1B and IL-6, that are correlated with the level of HbA1c.

  • Immune cell function

Evidence for altered function of monocytes and T-cells in diabetic patients with periodontitis is limited. Clinical and animal studies provide evidence of defective neutrophil function in diabetes and periodontitis, but the complexity of the functions of neutrophils and the diversity of the experimental results make precise identification of the functional changes and their relationship to pathogenesis difficult.

  • Hyperglycaemia and cellular stress

Average to poor glycaemic control, caused by elevated levels of protein kinase C and its activity, causes an increase in the number of neutrophils. Furthermore, hyperglycaemia can lead to oxidative stress through a number of routes with corresponding effects on inflammatory response, but there is insufficient evidence to establish a connection with the pathogenesis of periodontitis.

Reactive Oxygen Species (ROS) have effects on osteogenesis and also on a newly discovered metabolic pathway, Wnt signalling, and the activation of FoxO transcription factors in regulating osteoblast activity could link diabetes to periodontitis.

Hyperlipidaemia, which is common in diabetes and obesity, can also contribute to oxidative stress and exacerbate the effects of hyperglycaemia in the proinflammatory response.

Effects have also been observed in other cell types, such as decreased collagen production and increased collagenolytic activity of gingival and periodontal ligament fibroblasts and extreme inflammatory response by oral epithelial cells.

  • Hyperglycaemia, advanced glycation end products (AGEs) and their receptor (RAGE)

A chronic effect of hyperglycaemia, comprising the enzymatic glycosylation of proteins and lipids, leads to the formation of AGEs. These AGEs can cause cellular stress by promoting proinflammatory / oxidative effects directly or through interaction with cell surface receptors, including periodontitis. The expression of AGEs could be significantly associated with the extent of periodontitis in DM2 patients.

AGEs can also interact with TLR2, TLR4 and TLR9 receptors in the gingival tissues of periodontitis patients with diabetes, and tend to be higher than in periodontitis patients not suffering from diabetes. These receptors, particularly TLR4, are also involved in proinflammatory responses.

Hyperglycaemia and diabetes lead to the irreversible formation of AGEs, which has pro-inflammatory and pro-oxidant effects on cells. When AGEs bind to its receptors, RAGE, inflammation and oxidative stress further increase, worsening the restorative function of tissues and increasing periodontal tissue destruction. Periodontitis worsens these effects.

  • Hyperglycaemia and alveolar bone homeostasis

Hyperglycaemia in patients with diabetes may regulate the RANKL / OPG bone resorption mediator rate in periodontal tissues, and this could partly explain why alveolar bone destruction is greater in diabetes patients.

It has been observed that AGE-RAGE might contribute to osteoclastogenesis and to the duration of inflammatory response, via an increase in RANKL expression, and to decreased OPG, besides gingival cytokine IL-17 and IL-23 activity.

b) The impact of Periodontal disease on diabetes

  • Microbial factors

It has been observed that both glycaemic control and cytokine induction (particularly IL-1B, IL-8, IL-12 and TNF-alpha) can be affected by P. gingivalis.

However, very few studies have determined the impact of periodontal microbiota on diabetes, and therefore, not enough evidence exists to suggest that periodontal microbiota may have a direct impact on diabetic state or on glycaemic control.

  • Inflammatory factors

Dysregulation of peripheral cytokine pool in DM1 and DM2 is considered a main pathogenic factor in diabetes. Circulating mediators (CRP, TNF-alpha and IL-6) may increase in the presence of periodontal disease.

Therefore, periodontal inflammation could have an effect on diabetic state.

Below is an overview of the correlation between diabetes-induced physiological/metabolic processes and their possible impacts on periodontitis:


Patients with diabetes have 2 to 3 times the risk of developing chronic periodontitis. In fact, periodontal disease is considered to be the sixth complication of diabetes after hypertension, stroke, heart disease, kidney disease and retinopathy.

Haemoglobin A1c (HbA1c) reflects the levels of serum glucose, and is therefore a direct parameter for measuring glycaemic control. HbA1c control is adversely affected by systemic inflammation. Therefore, if an effective treatment for periodontitis can modify glycaemic control, periodontal treatment may contribute to patient treatment programmes in relation to lifestyle changes and medication.

Thus, periodontal treatment could improve metabolic parameters, by measuring HbA1c. In a meta-analysis of studies conducted so far, we have obtained a mean reduction of 0.36% in HbA1c levels among treatment groups. Given that the majority of patients with DM2 take medication besides metformin, and that scaling and root planing can improve metabolic control by almost 0.4%, this effect can be compared to the effects of additional medication besides metformin.

It is also important to keep in mind that when periodontal treatment is performed in conjunction with systemic antibiotics, these can potentially mask the effects of scaling and root planing by controlling HbA1c, because they can also act against non-oral sources of infection. Therefore, a decrease in HbA1c levels may possibly not be attributed only to a local reduction of the periodontal bacterial load. Furthermore, this decrease could reduce the risk of diabetes-related complications such as retinopathy, nephropathy and neuropathy.

The main limitation is the absence of multicenter randomized clinical trials involving large populations to validate these results. Other limitations include disease definition and the ultimate goal of treatment.

  1. Chapple ILC, Genco R, and on behalf of working group 2 of the joint EFP/AAP workshop. Diabetes and periodontal diseases: consensus report of the Joint EFP/ AAP Workshop on Periodontitis and Systemic Diseases. Journal of Clinical Periodontology; 40 (Suppl. 14): S106–S112.
  2. Borgnakke WS, Ylöstalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. Journal of Clinical Periodontology; 40 (Suppl. 14): S135–S152.
  3. Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. Journal of Clinical Periodontology; 40 (Suppl. 14): S113–S134.
  4. Engebretson S, Kocher T. Evidence that periodontal treatment improves diabetes outcomes: a systematic review and meta-analysis. Journal of Clinical Periodontology; 40 (Suppl. 14): S153–S163.