Association between Periodontitis and Hyperglycemia

Objective The objective of this study was to analyze the prevalence of undiagnosed hyperglycemia in individuals with periodontitis. Methods The sample was composed of randomly selected individuals that had signed-up for treatment at the Newton Paiva University dental clinic. The volunteers were divided in two groups, the first composed by individuals without periodontitis (n = 30) and the second by individuals with periodontitis (n = 20). All participants answered a questionnaire about habits and overall health condition. Salivary flow was quantified and periodontal examination evaluated bleeding when probed, probing depth and clinical attachment level. Through laboratory tests, the fasting glucose and the glycated hemoglobin levels were quantified. Results In the sample studied a higher percentage of individuals with hyperglycemia among those with periodontitis than those without periodontitis was identified. Conclusion It is suggested, therefore, that the request of laboratory tests to check glucose levels becomes a part of the dental treatment protocol of individuals with periodontitis. Indexing terms: Complications. Diabetes Mellitus. Periodontitis.


INTRODUCTION
Diabetes Mellitus (DM) constitutes of a group of alterations characterized by hyperglycemia, resulting from the deficiency of production and/or resistance to the role of insulin [1].It represents one of the main public health problems, being the fourth cause of death in Brazil [2].DM is classified, according to its etiopathogeny, in type 1 DM, type 2 DM, gestational DM and other specific types [3].
According to the World Health Organization, the average prevalence of DM worldwide is of 10% [4].In Brazil, nearly five million individuals are diabetic, having an expectancy of a 50% increase to that number by 2025 [5].According to studies made by the Ministry of Health, the total number of individuals with the disease increased 40% between 2006 and 2012 [6].Around the world, nearly 4 million deaths per year are directly related to DM, since it also favors the worsening of systemic diseases [7,8].
Hyperglycemia contributes for the development of classic complications associated to DM, such as visual changes, nephropathies, cardiovascular diseases, neuropathies, susceptibility to infections and periodontitis [3].
Immune-inflammatory alterations present in diabetic individuals increase the susceptibility of developing periodontitis, inflammatory disease that affects the supporting tissues of the teeth, being considered the sixth classic complication of DM.Epidemiological studies have emphasized that DM is a risk factor for periodontitis, increasing its probability of occurring by three times [9,10].DM is also associated with greater severity of periodontitis [11].The immune-inflammatory process resulting from the bacterial aggression, is the main responsible for the damage observed on the periodontal tissues, clinically characterized by bleeding to probing (BP), increase in probing depth (PD) and insertion loss, followed by bone tissue destruction.The evolution of periodontitis may eventually lead to loss of the dental element [12,13].
The present study aims to evaluate the prevalence of hyperglycemia not yet diagnosed in individuals with periodontitis.

Sample
The convenience sample was composed by 50 randomly selected individuals from those that had signed up for dental treatment at the Newton Paiva University Center dentistry course, between the months of August and November 2015.The individuals were subdivided into two groups: without periodontitis (n=30) and with periodontitis (n=20).All the participants were informed about the objectives of the study and were only included as part of the study after manifesting interests by signing an informed consent form (ICF).
The inclusion factors were the presence of a minimum of 12 teeth, 18 years of age or older and absence of any contraindication for periodontal examination.Any individuals previously diagnosed with DM, submitted to antibiotic therapy or periodontal therapy during the last three months and carriers of the acquired immune deficiency syndrome (AIDS), were excluded.
The study was previously submitted and approved by the Ethics Committee under the number CAAE 37644314.6.0000.5097.

Behavioral and biological social characteristics
With a structured questionnaire, the following data were collected: gender, age, tobacco use, hypertension and family history of DM.The participants were also questioned about the presence of the following symptoms that are characteristic to DM: polydipsia, polyuria, polyphagia, unexplained wait loss and visual alteration.

Medical data
Weight and height of the participating individuals were registered to calculate the body mass index (BMI).According the BMI the individuals were classified as underweight (BMI below 18.5), normal weight (BMI between 18.5 and 24.9), overweight (BMI between 25.0 and 29.9) and obesity (BMI above 30.0)[4].
All the participants performed, at the same laboratory, the fasting glycaemia and glycated hemoglobin (A1c) exams.Glycaemia was considered altered for fasting glycaemia and glycated hemoglobin values above 99mg/dL and 5.6%, respectively [3].

Sialometry
Sialometry was employed for quantitative analysis of resting and stimulated saliva.In order to collect the saliva the participants remained 30 minutes without eating or drinking and 2 minutes without performing any chewing, swallowing or talking movements.For resting and stimulated sialometry, the individuals collected, Periodontitis and Hyperglycemia in a millimeter tube, all the saliva produced during 5 minutes.During the stimulated sialometry the individuals chewed on sialogogo.The quantity of saliva and foam produced was verified directly on the collector during the five minutes.The total volume collected was divided by 5, obtaining a result in mL/min.The participants were grouped, according to the obtained salivary flow, in normal (flow from 1.5 to 3.0 mL/min), hypossalivation (flow from 0.05 to 1.45 mL/min) and sialorrhea (flow above 3.0 mL/min) [14].

Periodontal clinical examination
The periodontal exam was performed to analyze the clinical parameters of BP, PD and clinical attachment level (CAL) of all teeth present.Mesial, distal, buccal and lingual measurements were registered for each tooth.The periodontal exam was performed by two researchers (MTGO and PGSF), who were previously calibrated, using a millimeter probe, model UNC-15 North Carolina (Hu-Friedy, Chicago, USA).
The inability to determine the cementoenamel limit, presence of gingival morphology alteration, extensive carious lesion, iatrogenic restorative procedures or excess calculus that could difficult the periodontal exam were considered exclusion criteria for the teeth [15].
The bleeding exam was conducted while probing, by gently and carefully introducing the probe into the gingival sulcus until reaching its base.The bleeding was analyzed 30 to 60 seconds after probing.The occurrence of BP was registered for each surface in a dichotomy manner, indicating its presence or absence.The probing depth was obtained by measuring the distance from the gingival margin to the sulcus base or periodontal pocket.The CAL was determined by the distance between the cementoenamel junction and the periodontal sulcus or pocket base.The criteria used to diagnose periodontitis was the presence of four or more teeth with at least one site PD ≥ 4 mm and CAL ≥ 3 mm associated to BP at the same site [16].

Statistical analysis
The comparison between the groups for the variables of interest was performed by the Chi-square, Mann-Whitney and Fishers' Exact tests when appropriate.The results were considered significant with a probability below 5% (p < 0.05).All the statistical analysis was made with SPSS program (version 17.0).

RESULTS
Table 1 presents the characterization of the sample in the groups with and without periodontitis.The groups were considered similar according to the majority of the evaluated criteria.Among the DM symptoms investigated, visual alteration was more frequently reported by the individuals with periodontitis.The individuals from the group with periodontitis had significantly higher average fasting glycaemia than the individuals without periodontitis.However, when fasting glycaemia was categorically measured the difference was not maintained.The same occurred with glycated hemoglobin, when evaluated quantitatively and categorically.The participants with periodontitis presented a 97.7 mg/dL average fasting glycaemia, while for the participants without periodontitis the average was 85.5 mg/dL.The characterization of the periodontal condition of the sample in the groups with and without periodontitis is presented in table 2. As expected, individuals with periodontitis presented greater percent of locations with altered PD and with BP, although the total number of teeth were similar between groups.

DISCUSSION
DM is a prevalent condition with high rates of morbidity and mortality.Its early diagnosis can contribute to the reduction of associated diseases and an improvement in prognosis.The fact that DM presents, in the majority of cases, a chronic evolution makes it remain undiagnosed for a long period of time, until symptoms and classic complications manifest themselves [9].Periodontitis is a known complication to DM [17,18] and can aid in the detection of undiagnosed hyperglycemia.
The results from the present study evidence that individuals with periodontitis present increased levels of blood glucose than individuals without periodontitis.Average fasting glycaemia values were higher for individuals with periodontitis when compared to individuals without periodontitis.Although there was no statistical significance,  When the sample was characterized considering the groups of patients with normal and altered fasting glycaemia (table 3), the individuals with altered fasting glycaemia presented greater PD, prevalence of periodontitis and lower amount of teeth present, although these differences were not statistically significant.The percent of sites with BP was statistically higher for the group with altered fasting glycaemia (p=0.007).For the analysis of the sample considering the groups of individuals with normal and altered glycated hemoglobin there was no statistically significant difference between the groups with regards to the evaluated periodontal parameters, with exception to the number of teeth which was significantly higher in the group of individuals with normal levels of glycated hemoglobin (table 4).
Periodontitis and Hyperglycemia glycated hemoglobin levels were more elevated in individuals with periodontitis.The reduced sample size is a limitation to the study that can explain the difference among the statistical results for the fasting glycaemia and glycated hemoglobin exams.However, the two exams present high level of agreement and are indicated for diagnosis of hyperglycemia [3].
Due to the multifactorial character of DM, scientific studies must consider the presence of confounding variables that could compromise the results.Increased age and high BMI, for example, are considered risk factors for DM [19].In this study, however, the individuals with and without periodontitis were considered to be similar with regards to age and BMI, which increases the credibility in the obtained results.
In contrast, smoking is a risk factor for periodontitis [20].The habit of smoking interferes on the pathogenesis of periodontitis by altering vascularization, immuneinflammatory response and homeostasis of the tissues, increasing the susceptibility to the disease and causing greater destruction of periodontal tissues [21].In the present study there was a greater prevalence of smokers in the group with periodontitis, although this difference was not statistically significant.
Additionally, DM is proved to be a risk factor for periodontitis.Immune and inflammatory system alterations are associated to the prevalence and increased severity of periodontitis in individuals with hyperglycemia.The neutrophils have reduced functioning, while monocytes and macrophages are found to be hyper reactive with increased production of proinflammatory cytocines [22].The results evidenced that the prevalence of periodontitis was bigger for individuals with increased glycemic levels, although not statistically significant.Again, the reduced sample size could have affected the identification of the statistical significance.
Even though periodontitis is the most prevalent DM oral complication, some studies have also shown a reduction to salivary flow in individuals with hyperglycemia [17].However, the elevated age that is a risk factor for diabetes must be considered because it may be associated to the reduction of salivary flow, which could difficult result interpretation [19].On the other hand, other studies have not identified salivary flow reduction among diabetic individuals.In the present study there was not salivary flow difference between groups with or without periodontitis.

CONCLUSION
Periodontitis is a classic complication of DM and its presence can help identify glycemic alterations not yet diagnosed.In the sample studied a greater prevalence of individuals with undiagnosed hyperglycemia in the group with periodontitis was identified.Therefor, dental appointments can be opportune moments to monitor periodontal patients' glycemic levels.It is believed that periodontitis diagnosis can be an important indicator of the presence of hyperglycemia and a tool capable of identifying future candidate to develop DM.It is suggested, therefore, that the request of exams to evaluate glycemic levels becomes part of the dental appointment service protocol of individuals with periodontitis.

Collaborators
MTG OLIVEIRA, bibliographic gathering, creation of forms for data collection, data collection and periodontal examination, creation of the database, writing of the final article.PGS FURTADO, bibliographic gathering, creation of forms for data collection, data collection and periodontal examination, creation of the database, writing of the final article.RFC CARDOSO, bibliographic gathering, data collection and periodontal examination, creation of the database, writing of the final article.ACD SOUZA, study design, bibliographical gathering, supervision of examining researchers, writing of the final article, review of the article.RPE LIMA, study design, bibliographical gathering, creation of forms for data collection, calibration of grant students and volunteers, supervision of examining researchers, statistical analysis of the data, writing of the final article and article submission.SMS MENDONÇA, study design, bibliographical gathering, creation of forms for data collection, calibration of grant students and volunteers, supervision of examining researchers, statistical analysis of the data, writing of the final article and article submission.

Table 1 .
Characterization of the sample groups with and without periodontitis.

Table 2 .
Characterization of the periodontal condition in the groups with and without periodontitis.

Table 3 .
Characterization of the periodontal condition of the sample for the groups with normal and altered fasting glycaemia.

Table 4 .
Characterization of the periodontal condition of the sample for the groups with normal and altered glycated hemoglobin.