Periodontitis: Diabetes Complication?

Periodontitis has been called the “sixth major complication” of diabetes, with research suggesting a bidirectional relationship between the two conditions.¹ Studies have suggested that diabetes may increase the risk of periodontitis between two to threefold. Periodontitis may also play a role in the development of diabetes, though the nature of this relationship has yet to be understood. The disease has also been linked to increased severity of diabetic complications, especially cardiovascular and renal disease.²

While predisposing factors for periodontitis include genetic susceptibility and smoking, increased systemic inflammation may also be involved.¹ The underlying mechanism is not completely understood, but the current thinking is that diabetes may increase inflammatory mediators in periodontal tissue, such as interleukin (IL)-1β, prostaglandin (PG)-E2, tumor necrosis factor (TNF)-α, and matrix metalloproteinases (MMPs). The resulting cytokine stimulation increases periodontal tissue injury and furthers disease progression.^1,2

Hyperglycemia also stimulates the formation of reactive oxygen species in periodontal tissues. The interaction between advanced glycation end products (AGEs) and their receptor (RAGE) may play an important role in diabetes complications, including periodontitis.^1,2

Diabetes may also change the local immune environment in periodontal tissues, resulting in subtle differences in the microbiota in periodontal pockets.³

Research has also suggested that periodontal therapy may improve glycemic control by about 0.4%, according to a past Cochrane Review.⁴ One explanation holds that periodontal tissue releases inflammatory mediators into the systemic circulation, and these mediators may interfere with insulin signaling and glucose homeostasis.¹

However, in January 2014, results from the Diabetes and Periodontal Therapy Trial (DPTT), the largest randomized controlled trial to assess the impact of nonsurgical periodontal treatment on glycemic control, called this issue into question.⁵ The 6-month, 5-center trial included 514 participants with moderate to severe periodontitis and T2DM. Participants were randomized to nonsurgical periodontal therapy or no treatment. Recruitment was ended early after interim results revealed no significant difference in glycemic control between treatment and control groups. Researchers concluded that the results did not support a role for nonsurgical periodontal treatment for the purposes of improving glycemic control. 

These results came on the heels of a consensus report on periodontitis and systemic diseases issued in December 2013 by the European Foundation for Periodontology (EFP) and the American Academy of Periodontology (AAP). That report cited evidence that treating severe periodontal disease with nonsurgical therapy may result in a HbA1c reduction roughly equivalent to adding a second antidiabetes medication, and offered oral health guidelines for diabetic patients.⁶

The EFP responded to the DPTT results by issuing a statement highlighting several flaws in the study. The crux of the matter concerned periodontal outcomes, which the EFP believed were not clinically relevant. Without adequate control of periodontal infection, the effects of periodontal treatment on glycemic control cannot be properly ascertained, they argued.⁷

Soon after, a group of researchers issued a critical review, highlighting three main concerns from the study: baseline HbA1c already near goal, periodontal treatment not reaching the accepted standard of care, and “prominent” obesity in the treatment group.⁸

This controversy was covered in January 2014 and July 2014.

Since then, studies that have treated participants to a clinically successful periodontal endpoint have been published, Iain Chapple, PhD, College of Medical & Dental Sciences, Birmingham, UK, said in an email. Dr. Chapple was first author of the EFP/AAP report. These studies, as well as subsequent systematic reviews that include data from the DPTT trial, have shown significant improvements in HbA1c with periodontal treatment, he pointed out.

For example, a recent case-control study of 40 patients with periodontitis and T2DM found that effective nonsurgical periodontal therapy was associated with significantly improved insulin sensitivity, fasting blood glucose, and HbA1c at three months, compared to no treatment.⁹

And, a recent systematic review and meta-analysis of seven RCTs (including the DPTT trial) covering 940 patients found a reduction of glycated hemoglobin 0.48 (95 % CI: 0.18-0.78) after 3 months of nonsurgical periodontal therapy.¹⁰

However, an updated Cochrane Review, which included 35 RCTs published up to December 2014 and covered 2565 participants, found low quality evidence to support that periodontal treatment (scaling and root planning) improves glycemic control. At 3-4 months, the mean reduction in HbA1c was 0.29%, with insufficient evidence to suggest that this decrease was maintained after four months. Studies achieved varying degrees of success in periodontal endpoints. The review emphasized the need for larger, longer-term studies that achieve clinically effective periodontal endpoints.¹¹

Nevertheless, Dr. Chapple commented, “The EFP/AAP guidance has not changed, as the DPTT trial was unable to answer the question of whether treating periodontal disease to defined outcomes of success (rather than periodontal treatment failure) improves HbA1C.”

In early 2017, the EFP will be meeting with the International Dental Forum (IDF), in order to develop consensus guidelines based on the latest research.

Take-home Points

• Periodontitis has been called the sixth major complication of diabetes, with research suggesting a bidirectional relationship between the two conditions.

• Systemic inflammation may underlie the two-way relationship between periodontitis and diabetes.

• Studies have suggested that periodontal therapy may improve glycemic control, though the largest RCT to date has questioned this issue.

• Experts emphasize the importance of treating periodontitis to clinically meaningful endpoints in order to assess improvements in glycemic control, and plan to meet in early 2017 to draw up new guidelines.

References:

1. Gurav AN. Management of diabolical diabetes mellitus and periodontitis nexus: are we doing enough? World J Diabetes. 2016 Feb 25;7(4):50-66.

2. Casanova L, et al. Periodontitis and diabetes: a two-way relationship. Br Dent J. 2014;217:433-437.

3. Preshaw PM, et al. Periodontitis and diabetes: a two-way relationship. Diabetologia. 2012;55:21.

4. Simpson TC, et al. Treatment of periodontal disease for glycaemic control in people with diabetes. Cochrane Database Syst Rev. 2015 Nov 6;(11):CD004714. 

5. Engebretson SP, et al. The effect of nonsurgical periodontal therapy on hemoglobin A1c in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial.  JAMA. 2013;310:2523-2532.

6. Chapple ILC, et al. Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Periodontol. 2013;84(4 Suppl):S106-S112. Accessed online on October 27 2016 at: http://onlinelibrary.wiley.com/doi/10.1111/jcpe.12077/pdf.

7. European Federation of Periodontology. Official Statement on NIH Study. December 18, 2013. Personal email communication with Iaian Chapple

8. Borgnakke WS, et al. The randomized controlled trial (RCT) published by the Journal of the American Medical Association (JAMA) on the impact of periodontal therapy on glycated hemoglobin (HbA1c) has fundamental flaws. J Evid Base Dent Pract. 2014 Sep;14(3):127-132.

9. Mammen J, et al. Effect of non-surgical periodontal therapy on insulin resistance in patients with type II diabetes mellitus and chronic periodontitis, as assessed by C-peptide and the Homeostasis Assessment Index. J Investig Clin Dent. 2016 Jun 10.

10. Teshome A, Yitayeh A. The effect of periodontal therapy on glycemic control and fasting plasma glucose level in type 2 diabetic patients: systematic review and meta-analysis. BMC Oral Health. 2016 Jul 30;17(1):31.

11. Simpson TC, et al. Treatment of periodontal disease for glycaemic control in people with diabetes mellitus. Cochrane Database Syst Rev. 2015 Nov 6;(11):CD004714.