The relationship between periodontal diseases and diabetes: an overview

Diabetes mellitus, caused by the malfunction of insulin-dependent glucose and lipid metabolism, presents with the classical triad of symptoms: polydypsia, polyuria, and polyphagia which are often accompanied by chronic fatigue and loss of weight. Complications of diabetes mellitus include retinopathy, nephropathy, neuropathy, and cardiovascular disease. Periodontal diseases are infections affecting the periodontium and resulting in the loss of tooth support. The association between diabetes mellitus and periodontitis has long been discussed with conflicting conclusions. Both of these diseases have a relatively high incidence in the general population (diabetes 1% to 6% and periodontitis 14%) as well as a number of common pathways in their pathogenesis (both diseases are polygenic disorders with some degree of immunoregulatory dysfunction). On the one hand, numerous reports indicate a higher incidence of periodontitis in diabetics compared to healthy controls, while other reports fail to show such a relationship. Clarification of this dilemma is occurring as the diagnostic criteria for periodontitis and diabetes mellitus improve, controlled studies with increased sample sizes are carried out, and the studies take into account major confounding variables that impact on the pathogenesis of both diseases. Current studies tend to support a higher incidence and severity of periodontitis in patients with diabetes mellitus. The overview looks at the bidirectional relationship between periodontitis and diabetes. An analysis of the National Health and Nutrition Examination Survey (NHANES) III data set confirms the previously reported significantly higher prevalence of periodontitis in diabetics than in non-diabetics (17.3% versus 9%). The analysis of the data also shows that the prevalence of diabetes in patients with periodontitis is double that seen in the non-periodontitis patients (12.5% versus 6.3%) and that this difference is also statistically significant. The pathogenesis of the 2 diseases is reviewed with an emphasis on common genetic and immune mechanisms. On the basis of the overview, 2 hypotheses for testing the relationship between periodontitis and diabetes are discussed. The first proposes a direct causal or modifying relationship in which the hyperglycemia and hyperlipidemia of diabetes result in metabolic alterations that may then exacerbate bacteria-induced inflammatory periodontitis. The second hypothesis proposes that a fortuitous combination of genes (gene sets) could result in a host who, under the influence of a variety of environmental stressors, could develop either periodontitis or diabetes or both.     

Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective

This review evaluates evidence for a bidirectional relationship between diabetes and periodontal diseases. A comprehensive Medline search of the post-1960 English language literature was employed to identify primary research reports of relationships between diabetes and periodontal diseases. Reports included in the review on the adverse effects of diabetes on periodontal health (DM-->PD) were restricted to those comparing periodontal health in subjects with and without diabetes. Review of adverse affects of periodontal infection on glycemic control included reports of periodontal treatment studies and follow-up observational studies in which changes in glycemic control could be assessed. Observational studies reporting DM-->PD provided consistent evidence of greater prevalence, severity, extent, or progression of at least one manifestation of periodontal diseases in the large majority of reports (supportive evidence in 44/48 total reviewed; 37/41 cross-sectional and 7/7 cohort). Additionally, there were no studies reviewed with superior design features to refute this association. Treatment studies provided direct evidence to support periodontal infection having an adverse, yet modifiable, effect on glycemic control. However, not all investigations reported an improvement in glycemic control after periodontal treatment. Additional evidence to support the effect of severe periodontitis on increased risk for poorer glycemic control comes from 2 follow-up observational studies. The evidence reviewed supports viewing the relationship between diabetes and periodontal diseases as bidirectional. Further rigorous, systematic study is warranted to establish that treating periodontal infections can be influential in contributing to glycemic control management and possibly to the reduction of the burden of complications of diabetes mellitus.     

Th1/Th2/Th17/Treg Balance in Apical Periodontitis of Normoglycemic and Diabetic Rats

IntroductionThe aim of this study was to evaluate the inflammatory profile of T helper (Th) cells in normoglycemic (N) and diabetic rats with apical periodontitis (AP).MethodsTwenty male Wistar rats were divided in 2 groups: N rats and rats with diabetes mellitus (DM). DM was induced using streptozotocin, and AP was induced by dental pulp exposure of the first mandibular molar to the oral environment. After 30 days, the mandibles were removed and processed for histologic analysis, bacterial analysis, and immunochemical assays for interleukin (IL)-6, tumor necrosis factor alpha, IL-17, IL-23, interferon gamma, and IL-10. The Mann-Whitney U test and Student t test were used for statistical analysis (P < .05).ResultsThe DM group showed more intense inflammatory infiltrate with larger sizes of bone reabsorption and a greater presence of bacteria than the N group (P < .05). Proinflammatory cytokine levels in the DM group were also greater than those in the N group (P < .05). However, interferon gamma was more intense in the N group than in the DM group (P < .05).ConclusionsThe inflammatory profile of AP in DM is different from that in the N group, suggesting that Th1 is a secondary strain and the Th17 strain is predominant in DM.     

A population-based study of periodontal care among those with and without diabetes

Background: Our objectives were to describe the prevalence of periodontal care (a marker of periodontitis) among persons with and without diabetes and to examine the association between periodontal care and diabetes. Methods: We conducted a cross‐sectional analysis, using 5 years of electronic data from a population‐based cohort (N = 46,132), aged 40 to 70 years, with dental and medical insurance, and ≥1 dental and ≥1 medical visit. Periodontal care (yes/no) was defined by dental claims codes for procedures used to manage periodontitis. The association between periodontal care and diabetes was determined using logistic regression adjusted for and stratified by age, sex, insurance type, smoking status, body mass index (BMI) (in kilograms per square meter), and resource utilization band (RUB) (a measure of expected health care utilization attributable to comorbidity). Results: Overall, 11.2% (5,153 of 46,132) met diabetes criteria. The age‐adjusted prevalence of periodontal care among those with and without diabetes was 39.1% and 32.5%, respectively (P <0.0001). The association between diabetes and periodontal care decreased with increasing age (interaction, P <0.0001), adjusting for BMI and RUB. The aged‐stratified, adjusted odds ratio (OR) for periodontal care associated with diabetes was highest among those aged 40 to 44 years [OR, 1.6; confidence interval (CI), 1.30 to 1.97] and lowest among those aged 60 to 64 years (OR, 0.97; CI, 0.81 to 1.15) and was significant only among those aged 40 to 54 years. Conclusion: We found that the prevalence of periodontal care was significantly higher among those with diabetes compared to those without diabetes and that the magnitude of this association decreased with increasing age.     

Salivary and Serum Markers Related to Innate Immunity in Generalized Aggressive Periodontitis

Background: Host inflammatory and immune responses play an important role in aggressive periodontitis (AgP). Thus, this study aims to evaluate levels of the innate immunity‐related markers calprotectin, colony‐stimulating factor (CSF)‐1, macrophage migration inhibitory factor (MIF), monokine induced by interferon‐γ (MIG), and matrix metalloproteinase (MMP)‐8 in serum and saliva from patients with generalized AgP and those with gingivitis or a healthy periodontium. Methods: This study enrolled 40 individuals (17 males and 23 females; mean age 33.30 ± 9.31 years), 15 with generalized AgP, 15 with gingivitis, and 10 who were periodontally healthy. Full‐mouth periodontal examinations were performed, and serum and saliva were collected. Levels of calprotectin, CSF‐1, MIF, MIG, and MMP‐8 were measured using enzyme‐linked immunosorbent assays. Results: In serum, mean levels of calprotectin were 2.06‐fold higher in patients with AgP than in healthy patients (P = 0.01). Serum levels of MMP‐8 were significantly elevated in patients with AgP compared with both healthy patients and those with gingivitis, by 2.60‐fold and 2.77‐fold, respectively (P = 0.03 and P = 0.009, respectively). In saliva, levels of MMP‐8 were 5.66‐fold higher in patients with AgP than in healthy patients (P = 0.02). CSF‐1, MIF, and MIG levels in both serum and saliva did not differ significantly among the groups. Conclusions: Serum levels of calprotectin and MMP‐8 are elevated in patients with AgP. MMP‐8 levels are also increased in saliva from patients with AgP. These results support involvement of innate immune response in the pathogenesis of AgP.     

Periodontitis and gestational diabetes mellitus: exploring the link in NHANES III

OBJECTIVES: The authors hypothesized that women with a history of gestational diabetes mellitus (GDM) during pregnancy would exhibit more severe periodontal disease than controls without a history of diabetes during pregnancy. METHODS: Data from NHANES Ill provided information for 4,244 women ages 20-59. One hundred and thirteen had a history of GDM (GDM+), while 4,131 had no history of diabetes before or during their pregnancies (GDM-). Women were further classified by the presence or absence of diabetes mellitus (DM+ or DM-) at the time of their NHANES Ill examination. Periodontal disease (PD) was defined as one or more teeth with one or more sites with probing depth > or = 4mm, loss of attachment > or = 2mm, and bleeding on probing. RESULTS: The PD prevalence among women who were GDM+DM- was 9.0% and 4.8% for those who were GDM-DM-. PD prevalence for women who were GDM+DM+ was 30.5% and 11.6% for GDM-DM+ subjects, respectively. A logistic regression model, controlling for age, calculus, smoking, and income estimated women who were GDM+DM+ were more likely to have periodontal disease than women who were GDM-DM- and women who were GDM-DM+. The GDM+DM- group also tended to be more likely to have PD than the GDM-DM- and GDM-DM+ groups. However, the odds ratios were not statistically significant. CONCLUSIONS: These results support the hypothesis that women with gestational diabetes mellitus (GDM) during pregnancy may be at greater risk for developing more severe periodontal disease than pregnant women without GDM.     

The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease

Epidemiological studies have implicated periodontitis (PD) as a risk factor for development of cardiovascular disease (CVD). Persistent infections such as periodontitis induce inflammatory and immune responses which may contribute to coronary atherogenesis, and, in conjunction with other risk factors, may lead to coronary heart disease (CHD). In this review, mechanisms are described that may help explain the association between periodontal infections and CHD. Periodontal diseases are bacterial infections associated with bacteremia, inflammation, and a strong immune response, all of which may represent significant risk factors for the development of atherogenesis, CHD, and myocardial infarction (MI). Several mechanisms may participate in this association, including those induced by oral organisms, and those associated with host response factors. This review will focus on host factors. Oral pathogens and inflammatory mediators (such as interleukin [IL]-1 and tumor necrosis factor [TNF]-alpha) from periodontal lesions intermittently reach the bloodstream inducing systemic inflammatory reactants such as acute-phase proteins, and immune effectors including systemic antibodies to periodontal bacteria. This review will describe the potential role of various inflammatory as well as immunologic factors that may play a role in periodontitis as a possible risk factor for CHD.     

Periodontal and Systemic Responses in Various Mice Models of Experimental Periodontitis: Respective Roles of Inflammation Duration and Porphyromonas gingivalis Infection

Background: The great variability of periodontal and systemic responses to experimental periodontitis reflects the inherent pathogenic complexity of mice models and could limit the resulting interpretations and their extension to human diseases. This study compared the effect of Porphyromonas gingivalis (Pg) infection and experimental periodontitis duration at local and systemic levels in various models. Methods: Periodontitis was induced in C57BL/6J mice by ligatures previously incubated with Pg (LIGPG group) or not (LIG group) or by oral gavage (GAV) with Pg ATCC 33277. Blood samples were taken, and mice were euthanized at different times. Periodontal tissue destruction, osteoclast number, and inflammation were assessed by histomorphometry, tartrate‐resistant acid phosphatase histoenzymology, and cathepsin B (CATB) and matrix metalloproteinase 9 (MMP9) immunochemistry. Serum levels of interleukin‐6 (IL‐6) and IL‐1β were measured using enzyme‐linked immunosorbent assay bioplex methods. Results: Periodontal tissue destruction and osteoclast numbers were significantly elevated in LIGPG models compared to LIG and GAV models. They increased with time with the exception of osteoclast numbers in the LIG model. CATB and MMP9 expression was related to bone destruction processes and Pg infection. The highest serum levels of IL‐6 and IL‐1β were observed in the LIGPG group. A decrease of IL‐6 and an increase of IL‐1β serum level were observed with time in LIGPG group contrary to LIG group. Conclusions: These data indicate that Pg infection worsened periodontal tissue destruction through specific pathogenic pathways and modified systemic response to periodontal inflammation. Furthermore, the blood cytokine response to ligature models showed their relevance for evaluating the systemic impact of periodontal disease.     

Ⅱ型糖尿病牙周炎及牙周基础治疗对其影响的现状研究

Ⅱ型糖尿病是引起慢性牙周炎的主要危险因素之一,慢性牙周炎增加了Ⅱ型糖尿病的患病风险,但至今为止糖尿病牙周炎的发病机制尚未明确。牙周基础治疗不仅可以改善牙周炎患者的牙周状况,而且在一定程度上改善了糖尿病牙周炎患者的血糖状况。随着分子生物学技术的不断发展,研究人员对糖尿病牙周炎疾病在微生物、免疫及炎症因子方面的研究不断深入,该文对糖尿病牙周炎的微生物指标,免疫、炎症因子指标,临床指标及牙周基础治疗对疾病的影响做一综述。     

Periodontitis prevalence and severity in Indonesians with type 2 diabetes

Background: The prevalence of diabetes mellitus type 2 (DM2) in Indonesia is high and still rising. Periodontitis is associated with DM2. No study has investigated this association in Indonesia, nor has any study investigated this association using a variety of methods to operationalize periodontitis. The present study compares prevalence and severity of periodontitis in patients with DM2 to healthy controls, using different methods to operationalize periodontitis. Methods: A total of 78 subjects with DM2 and 65 healthy control subjects underwent a full‐mouth periodontal screening assessing probing depth, gingival recession, plaque index, and bleeding on probing. Using these measurements, the prevalence and severity of periodontitis was operationalized in various ways. Differences in the prevalence and severity of periodontitis between subjects with DM2 and healthy subjects were analyzed using univariate analyses. In regression analyses, the prevalence and severity of periodontitis were predicted on the basis of DM2 presence, controlling for confounders and effect modification. Results: Prevalence of periodontitis was significantly higher in subjects with DM2 compared to healthy subjects, showing odds ratios of 5.0 and 6.1. Likewise, periodontitis severity was significantly higher in subjects with DM2. Conclusion: Indonesian subjects with DM2 had more prevalent and more severe periodontitis than healthy Indonesian subjects, independent of confounding factors or the methods used to operationalize periodontitis.