In Brief Periodontitis has been identified as the sixth complication S E T E B A I D D N A of H T L A E . H L A R O / E C I T C A R P O T H C R A E S E R M O R F Advanced glycation end-products, altered lipid mechanisms, oxidative stress, and systemically elevated cytokine levels in patients with diabetes and peri- odontitis suggest that dental and medical care providers should coordinate therapies.

Diabetes and Periodontal : An Update for Health Care Providers

Inflammation of the dence of loss of support that is Periodontitis is a chronic inflamma- often seen as spreading of teeth result- G. Rutger Persson, DDS, PhD tory disease of the mouth that involves ing in open spaces between the teeth (Odont Dr) the gingiva (gum tissues), teeth, and (diastemas). Despite similar plaque supporting . Periodontitis is clini- scores (bacterial deposits), patients cally defined as the loss of connective with poorly controlled type 2 diabetes tissue attachment to the teeth and display more severe gingival bleeding alveolar bone loss. If periodontitis is compared to those with diabetes in left untreated, the involved teeth will good or moderate control.2 Patents exfoliate. with poorly controlled type 2 diabe- In many cases, periodontitis is the tes are at greater risk for periodontal second stage of an inflammatory pro- disease progression than patients with cess that begins with . From well-controlled type 2 diabetes.3 a clinical perspective, gingivitis pres- Treatment of chronic periodon- ents with swollen tissues and increased titis usually includes redness but with no loss of connective instructions, information on the role tissue attachment between root sur- of diet, and professional cleaning of faces and bone. The inflammatory cell the teeth and gum tissues using hand infiltrate in gingivitis is dominated by instruments or ultrasonic devices. In a polymorphonuclear neutrophil infil- trate (acute ), whereas addition, antibacterial mouth rinses, the histopathology of periodontitis is local or systemic , and sur- dominated by a plasma cell infiltrate (chronic inflammation).1 The clinical signs of periodontitis include swelling, redness and bleeding from the , spacing between teeth, loose teeth, and exposure of root sur- faces through loss of bone around the teeth. The disease can present locally, involving a few teeth, or be more gen- eralized. Figure 1 shows the severity of gingival inflammation in a patient Figure 1. Example of severe peri- who had received initial periodon- odontitis in an African-American tal non-surgical treatment 3 months patient with uncontrolled dia- before the photo was taken. betes (A1C > 9.0%) who has not In patients with a systemic disease responded to initial periodontal such as diabetes, the disease is often therapy. Notice the extent of spacing more generalized. Patients with poor between teeth and the severe inflam- glycemic control often present with mation (redness of gum tissues) and severely inflamed gum tissues and evi- (bacterial deposits). Diabetes Spectrum Volume 24, Number 4, 2011 195 gical intervention may be included in periodontal therapy.

Prevalence of Gingivitis and Periodontitis in Relation to Diabetes The prevalence of periodontitis in the United States is subject to controversy. Current data suggest that the preva- lence of periodontitis has decreased across ethnicity, sex, and age-groups to < 10%.4 Different interpretations of the same data suggest, however, that up to 50% of U.S. adults may suffer from various degrees of periodontitis.5 The prevalence of periodonti- tis is significantly higher among middle-aged people with diabetes than in similar-aged people without diabetes.6 Analysis of data from the third National Health and Nutrition Examination Survey has revealed that a self-reported family history of dia- betes, hypertension, high cholesterol, and clinical evidence of bears a probability of 27–53% that the patient has undiagnosed dia- betes.7 Analysis of periodontal status in people with type 1 or type 2 diabe- Figure 2. Levels of select bacteria associated with periodontitis in periodon- tes from a population-based German tal pockets of subjects without a diagnosis of diabetes and in subjects with study has demonstrated an association type 2 diabetes. A similar severity of periodontitis, but with lower bacterial between both types of diabetes and counts, was identified in subjects with diabetes for A. actinomycetemcomi- tooth loss.8 tans serotype Y4 (A.a (b) Y4), P. gingivalis, T. forsythia, and T. denticola, all Attention to oral disease in addi- associated with periodontitis. tion to medical conditions by both medical and dental care providers will than any other organ. Teeth provide a with periodontitis have a lipopolysac- improve the ability to identify individ- nonshedding surface with a complex charide (LPS) capsule with endotoxins uals unaware of their diabetic status. containing bacteria that are and heat-shock proteins. Pretreatment should establish referral pat- in balance with the host, but bacterial profiles of serum antibody titers to terns, communicate with physicians, species with high virulence can also different heat shock proteins and LPS and use dental screening as a tool for be identified. levels from Porphyromonas gingiva- referral of patients with severe gin- Periodontitis has a complex infec- lis, an anaerobe commonly found in gival or periodontal inflammation.9 tious etiology, and the establishment periodontitis lesions, can predict the It would be advantageous if blood of infection is usually slow. A bacterial outcome of periodontal therapy in glucose assessments were performed biofilm of both aerobic and anaero- patients with diabetes such that those in dental offices for patients at risk bic bacteria, including > 500 species, with elevated titers have a more favor- for type 2 diabetes. Likewise, physi- may be found in periodontal pockets able treatment outcome.14 cians should refer patients with type around teeth.11 Bacteremia is rarely Unpublished data based on 282 2 diabetes to dentists for treatment of identified in periodontitis. However, subjects, among whom 9.3% had gingival or periodontal inflammation. endotoxins from bacteria identified type 2 diabetes with similar severity This is especially important because in periodontal pockets and associ- of periodontitis, suggest that patients the pathophysiology of periodontal ated with periodontitis can be found with type 2 diabetes may have fewer inflammation is not limited to the oral in serum in > 30% of nondiabetic bacteria in periodontal pockets but cavity and can have important effects patients who present with early signs the same severity of disease. These on glycemic control. Indeed, periodon- of periodontitis.12 data suggest that the inflammatory titis has been identified as the sixth In general, the bacterial infec- response to infection in people with complication of diabetes.10 tion in periodontitis does not differ type 2 diabetes is more severe than in between nondiabetic patients and nondiabetic subjects (G.R.P, unpub- Pathophysiology of Periodontitis as a those with type 2 diabetes. However, lished observations). This may be Complication of Diabetes the immune response to periodon- explained by a lack of ability to pro- The oral cavity, as part of the gas- tal bacterial infection does differ in duce functional antibodies against trointestinal tract, is populated by that patients with type 2 diabetes do bacteria in periodontal infection. a diverse and large microbiota and not develop antibodies to pathogens This is illustrated in the diagram in has been identified as a location with associated with periodontitis.13 Many Figure 2, which includes four bacterial a more dense bacterial colonization of the anaerobic bacteria associated species associated with periodontitis. 196 Diabetes Spectrum Volume 24, Number 4, 2011 This observation is consistent with the oxidative stress.22 Clinical data have about the need for good oral health. general perception of an increased sus- suggested that the presence of AGEs Referral of patients S E with T E B A I D D N A uncontrolled H T L A E H L A R O / E C I T C A R P O T H C R A E S E R M O R F ceptibility to infection among patients in patients with diabetes is associated diabetes for dental evaluation and with type 2 diabetes. with the biofilm on teeth, indicat- periodontal treatment may result in Periodontal infections trigger the ing an increased risk for periodontal better control of blood glucose levels. release of pro-inflammatory cytokines damage.23 Although a survey of the oral cav- both at the site of the periodontal ity should be included in a thorough infection and throughout the endothe- Impact of Periodontal Therapies on medical examination, health care lial cell system.15 Studies of gingivitis Glycemic Control providers other than those within the in humans with or without type 1 From a Cochrane-based review, 24 dental team usually are not aware of diabetes have shown that both dia- the authors concluded that there what clinical signs of periodontitis betic and nondiabetic subjects react is some evidence of improvement to consider. An increased redness of to experimental plaque accumulation in metabolic control in people with the gum tissues along the teeth is a with gingival inflammation. However, diabetes after treatment of periodon- classic sign of gingivitis, a condition subjects with type 1 diabetes develop tal disease but also recognized that that indicates that there is an active an earlier and more severe local the evidence was weak because of inflammatory response to bacterial inflammatory response to a compa- statistical lack of power from avail- infection. The use of a or rable bacterial challenge.16 able studies. Data from another a toothpick to gently touch the gums Further studies have shown that meta-analysis of available literature of diabetic patients with inflammation two biological markers of inflamma- on periodontal intervention and the will provoke bleeding that will cease tion, IL-1b and MMP-8, which are effects on metabolic control in type within minutes. Health care provid- typically elevated in the fluid from 2 diabetic patients25 suggest that ers should suggest a thorough dental inflamed periodontal pockets, are periodontal intervention has posi- examination if such bleeding is com- more elevated in people with diabe- tive effects on blood glucose levels. mon throughout a patient’s mouth. tes.17 People with type 2 diabetes also In patients with A1C levels > 9.0%, Also, the presence of white or gray have higher levels of several other periodontal therapy may reduce A1C deposits on teeth suggests that dental cytokines (i.e., interferon-γ, osteo- by 0.6% in the absence of changes in treatment may be necessary. Spacing protegrin, tumor necrosis factor-α medication and by 1.4% if changes between upper front teeth and mobile (TNF- α), and interleukin 17 and 23) in diabetes medications are intro- teeth are other signs of periodontitis. at the site of periodontal infection but duced.26 After periodontal therapy, Likewise, dentists and dental also exhibit a downregulation of inter- a tendency toward a decrease of the hygienists should refer their patients leukin 4.18 TNF- α, A1C, soluble E-selectin, and who respond poorly to initial peri- An increasing severity of periodon- highly sensitive C-reactive protein lev- odontal therapy or have advanced titis has been linked to the development els in patients with diabetes has been periodontitis without obvious signs of of glucose intolerance,19 likely because demonstrated.27,28 poor oral hygiene for diabetes screen- of increased inflammation leading Periodontal therapy with adjunc- ing. In fact, it might be advantageous to increase in interleukin-6 (IL-6). tive systemic antimicrobial treatment for dental offices to monitor the blood The liver is an important target for may improve glycemic status of glucose levels of patients considered to IL-6 action, leading to an increased patients with uncontrolled type 2 be at risk for diabetes. inflammatory response with impaired diabetes by a decrease in serum A1C In summary: insulin signaling and action and resul- amounting to 0.2% from an average • Diabetes and periodontitis are tant decreased insulin production.20 of 9.9% before treatment.29 both common chronic Patients with impaired insulin produc- These findings are supported by in adults and specifically in older tion are therefore unable to control other investigators who identified that, individuals. for IL-6 activation and the enhanced although nonsurgical periodontal • There is substantial evidence of the inflammation induced by IL-6.20 therapy eliminates local and systemic impact of periodontitis on systemic Elevated IL-6 serum levels have been infection and inflammation via inflammatory markers. identified in people with untreated decreases in TNF-α, it is insuffi- • Periodontal treatment of patients chronic periodontitis.21 These studies cient alone for significantly reducing with diabetes may have limited suggest that the presence of elevated A1C levels without strict glycemic effects on slightly elevated A1C serum levels of pro-inflammatory control in poorly controlled diabetic levels, but in patients with more cytokines in patients with type 2 dia- patients.30 Thus, clinical collabora- severe diabetes, such treatment betes caused by periodontitis may tion between physicians and dentists may reduce A1C levels significantly aggravate inflammatory responses in is an important component of holistic if coordinated with blood glucose other organs commonly affected in successful treatment of patients with control. patients with diabetes. diabetes. • Signs of periodontal inflamma- Other pathological factors in dia- tion, including gingivitis, can betes affecting the periodontal tissue Conclusions be assessed easily by all medical are linked to elevated glucose levels in Patients with diabetes are usually health care providers. serum with development of advanced poorly informed about the relationship • Patients with periodontitis with glycation end-products (AGEs), altered between periodontitis and diabetes.31 severe gingival inflammation who lipid mechanisms, and oxidative stress. 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