Understanding the Inter-relationship Between Periodontitis and Diabetes: Current Evidence and Clinical Implications

Rachel A. Schallhorn, DDS, MS

Over the past few decades, the evidence base for periodontal-systemic inter-relationships has grown exponentially. Understanding the effect periodontitis exerts on systemic health, as well as clinical implications for management of patients with concurrent systemic disease, allows the dental practitioner to treat patients comprehensively with an emphasis on full-body health.

Diseases of the periodontium can impact systemic health through both direct and indirect mechanisms. Direct mechanisms involve bacteremia, or systemic dissemination of bacteria, originating from the oral cavity. Indirect mechanisms involve elevation of systemic inflammation resulting from inflammation of the supporting structures of the teeth. Just as periodontal disease has the potential to affect systemic health, uncontrolled systemic disease can influence the oral health of an individual and, specifically, periodontitis. Of the numerous periodontal-systemic inter-relationships studied, diabetes mellitus has been perhaps the most extensively evaluated.

Periodontitis has been referred to as the “sixth classic complication” of diabetes.¹ This article will focus on the evidence and implications of periodontitis related to type 2 diabetes.

Epidemiology of Periodontal Disease and Diabetes

Chronic disease is one of the most significant public health issues facing the US population. Aside from the impact on individual health and quality of life, treatment of chronic disease represents a substantial financial burden, accounting for approximately 86% of national healthcare costs in 2010.² Two of the most prevalent chronic diseases in the United States are periodontal disease and type 2 diabetes.

According to Centers for Disease Control and Prevention (CDC) data from the National Health and Nutrition Examination Survey, approximately 45% of the US population aged 30 years and older is affected with periodontitis. Furthermore, the prevalence of periodontal disease rises dramatically in older populations, with 68% of adults ≥ 65 years of age affected.³ In addition, 9.3% of the US population has diabetes, accounting for approximately 29.1 million individuals. Complications resulting from uncontrolled diabetes can lead to significant morbidity as well as premature death; the World Health Organization expects diabetes to become the seventh leading cause of death worldwide by the year 2030.⁴ Diabetes is the leading cause of kidney failure, lower-limb amputations (nontraumatic), and loss of vision,⁵ all of which significantly impact the affected individual’s quality of life.

Epidemiologic studies evaluating the association between periodontal disease and type 2 diabetes demonstrate a clear relationship. The strength of the association and the degree to which one disease affects the course of the other, however, is not clear. Systematic review and meta-analysis of epidemiologic studies evaluating the relationship between periodontal disease and diabetes suggest individuals with poorer periodontal health, as compared with those who are periodontally healthy, have an increased risk for developing diabetes, worsening glycemic control, and experiencing diabetes-related complications.⁶

Periodontitis–Diabetes Continuum

Central to both chronic diseases is dysregulation of the immuno-inflammatory response, leading to prolonged elevation of inflammation, which is somewhat self-perpetuating. While the mechanisms are not fully understood, it is through immuno-inflammatory pathways that periodontitis and diabetes have the potential to impact one another.

Periodontitis is initiated by bacteria and characterized by inflammation and destruction of the supporting structures of the teeth. While bacteria are necessary for development of the periodontal disease, the severity and progression is dictated by an individual’s inflammatory response. Severe periodontitis has been associated with elevated systemic inflammation as well as bacteremia, which activates the immune system. Furthermore, periodontal treatment is known to decrease the levels of inflammatory markers in the serum, particularly interleukin-6 (IL-6) and C-reactive protein (CRP).⁷

Type 2 diabetes is characterized by insulin resistance, leading to sustained elevation of blood glucose or hyperglycemia. In turn, insulin resistance is positively associated with systemic inflammation, and type 2 diabetes has shown a strong association with chronic systemic inflammation.⁸ Longitudinal studies have identified elevated IL-6 an CRP levels, also known to be associated with periodontitis, as risk factors for insulin resistance and type 2 diabetes.^9-11

Complications of diabetes are related to several mechanisms, including altered immune function,¹² impaired bone metabolism,¹³ and the formation of advanced glycation end-products (AGEs). The “classic” complications of diabetes include retinopathy, nephropathy, neuropathy, macrovascular disease, and deficient wound healing. A significant portion of these complications is attributable to AGE formation and accumulation. AGEs form when glucose irreversibly binds to proteins during sustained hyperglycemia. Examples of proteins that become glycated include serum albumin and collagen. Glycation of collagen, in particular, is thought to be related to the increased incidence and severity of periodontitis in patients with diabetes. Glycated collagen is less susceptible to enzymatic degradation, which can lead to decreased tissue turnover as well as accumulation of glycated collagen within vascular walls. Much like the microvasculature of the retina and glomerulus of the kidney are considered end-organs, the microvessels of the periodontium can also be thought of as an “end-organ” susceptible to AGE-related damage.

Aside from damage resulting directly from hyperglycemia, altered immune function contributes to the complications observed in patients with type 2 diabetes. Neutrophil adherence, chemotaxis, and phagocytosis are reduced, thus limiting bacterial killing and promoting periodontitis.¹⁴ Conversely, while neutrophil function is known to be impaired, macrophages and monocytes can become hyper-responsive and upregulate production of proinflammatory cytokines, which, in turn, increases systemic inflammation.¹⁵

Numerous studies have assessed the effect of treatment and control of periodontal disease and type 2 diabetes on one another within patient populations. A review of clinical studies demonstrates periodontal treatment can improve glycemic control; however, some investigations have demonstrated minimal-to-no effect. Recent meta-analyses and systematic reviews have indicated periodontal treatment has the potential to improve glycemic control in patients with type 2 diabetes.^16,17 The average reduction of HbA1c in the aforementioned studies ranged 0.36% to 0.65%. While the change appears relatively minimal, an HbA1c reduction of 1% is associated with a 30% decrease in microvascular complications related to diabetes.¹⁸

Examining the impact of diabetes on periodontal disease demonstrates a strong, positive association between worsening glycemic control and severity of periodontitis.7 In addition, epidemiologic studies indicate patients with well-controlled diabetes have a significantly lower risk for periodontitis as compared to individuals with poorly controlled diabetes.¹⁸

While the significance and strength of the association varies according to the available evidence, it is well accepted that uncontrolled diabetes can impact a patient’s periodontal health and stability over time. In addition, reducing periodontal inflammation can have a positive systemic impact and may aid in improving glycemic control, thus reducing the risk for complications over time.

Discussion and Conclusions

Dental professionals should understand the relationship between periodontal and systemic health, particularly the impact of untreated or uncontrolled periodontitis on systemic inflammation and physiology. Dental practitioners play a vital role in managing patients’ health over a lifetime. Recent data from the CDC indicate nearly half the people in the United States have periodontal disease. With an aging population, managing chronic disease will become an even larger portion of healthcare. As such, collaboration with medical colleagues is key to providing patients with comprehensive dental care, placing an emphasis on total-system health. Further research and collective efforts will continue to improve prevention and control strategies for both type 2 diabetes and periodontal disease. For example, recently published studies have identified potential value in assessing patients’ blood glucose levels in the dental office for screening and monitoring purposes. Identification of individuals with undiagnosed diabetes, in particular, holds significant value, especially as research suggests periodontitis is a risk factor for type 2 diabetes.^19,20

Treatment of periodontitis is known to reduce an individual’s systemic inflammatory burden. Reduction of systemic inflammation may, in turn, reduce the risk for complications of chronic disease. In the US population, chronic disease is reaching epidemic proportions. Minimizing risk is a key factor in preventing complications related to chronic disease over time. While the strength of the association between periodontitis and diabetes or other systemic diseases of inflammatory origin is difficult to quantify and is not fully elucidated, treating periodontitis and helping patients maintain periodontal health over a lifetime can reduce the systemic inflammatory burden and minimize overall risk for systemic disease and related complications.

About the Author

Rachel A. Schallhorn, DDS, MS
Private Practice
Aurora, Colorado

References

1. Löe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16(1):329-334.

2. Gerteis J, Izrael D, Deitz D, et al. Multiple Chronic Conditions Chartbook. Rockville, MD: Agency for Healthcare Research and Quality; 2014. AHRQ Publications No. Q14-0038.

3. Eke PI, Dye BA, Wei L, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015;86(5):611-622.

4. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442.

5. Centers for Disease Control and Prevention. National Diabetes Fact Sheet, 2011. Atlanta, GA: US Dept. of Health and Human Services, Centers for Disease Control and Prevention: 2011.

6. Borgnakke WS, Ylöstalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. J Periodontol. 2013;84(4 suppl):S135-S152.

7. Mealey BL, Oates TW; American Academy of Periodontology. Diabetes mellitus and periodontal diseases. J Periodontol. 2006;77(8):1289-1303.

8. Dregan A, Charlton J, Chowienczyk P, Gulliford MC. Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: a population-based cohort study. Circulation. 2014;130(10):837-844.

9. Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327-334.

10. Ndumele CE, Pradhan AD, Ridker PM. Interrelationships between inflammation, C-reactive protein, and insulin resistance. J Cardiometab Syndr. 2006;1(3):190-196.

11. Wang X, Bao W, Liu J, et al. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013;36(1):166-175.

12. American Academy of Periodontology. Diabetes and periodontal diseases [position paper]. J Periodontol. 1999;70(8):935-949.

13. Liu R, Bal HS, Desta T, et al. Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation. J Dent Res. 2006;85(6):510-514.

14. McMullen JA, Van Dyke TE, Horoszewicz HU, Genco RJ. Neutrophil chemotaxis in individuals with advanced periodontal disease and a genetic predisposition to diabetes mellitus. J Periodontol. 1981;52(4):167-173.

15. Naguib G, Al-Mashat H, Desta T, Graves DT. Diabetes prolongs the inflammatory response to a bacterial stimulus through cytokine dysregulation. J Invest Dermatol. 2004;123(1):87-92.

16. Engebretson S, Kocher T. Evidence that periodontal treatment improves diabetes outcomes: a systematic review and meta-analysis. J Periodontol. 2013;84(4 suppl):S153-S169.

17. Sgolastra F, Severino M, Pietropaoli D, et al. Effectiveness of periodontal treatment to improve metabolic control in patients with chronic periodontitis and type 2 diabetes: a meta-analysis of randomized clinical trials. J Periodontol. 2013;84(7):958-973.

18. Tsai C, Hayes C, Taylor GW. Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community Dent Oral Epidemiol. 2002;30(3):182-192.

19. Holm NC, Belstrom D, Ostergaard JA, et al. Identification of individuals with undiagnosed diabetes and pre-diabetes in a Danish cohort attending dental treatment. J Periodontol. 2016;87(4):395-402.

20. Harase T, Nishida W, Hamakawa, T, et al. Clinical implication of blood glucose monitoring in general dental offices: the Ehime Dental Diabetes Study. BMJ Open Diabetes Res Care. 2015;3(1):e000151. doi:10.1136/bmjdrc-2015-000151.