Reduction in HbA1c levels following non-surgical periodontal therapy in type-2 diabetic patients with chronic generalized periodontitis: A periodontist's role.

BACKGROUND: Aim of the study was to compare the response to non-surgical periodontal therapy between patients with and without type-2 diabetes from clinical and metabolic stand point.
MATERIALS AND METHODS: A comparative clinical study was performed between type 2 diabetics and non-diabetics with moderate generalized chronic periodontitis. The study period was six months. Conventional periodontal scaling and root planing were performed, and the response to this treatment was compared between the groups at three and six months, measuring the plaque index, bleeding index, gingival index, and probing depth. In diabetic patients, the clinical response was related to measurements of HbA1c and glucose in blood at three and six months. STATISTICAL ANALYSIS: Multi Variant Analysis of Variance was used to compare following variables between groups and function of time.
RESULTS: Improvement in all clinical variables was observed in both the groups. The improvement observed in blood HbA1c levels in diabetic group confirmed a positive metabolic response to non-surgical periodontal treatment.
CONCLUSION: With this study, we conclude that there is a definite reduction in HbA1c level in diabetic patients after conventional non-surgical periodontal treatment.

INTRODUCTION

Periodontal disease is the periodontal inflammatory process in which the primary etiologic factor may be microbiologic, systemic, or physical injury. It is a condition that affects and destroys the attachment apparatus.[1] Periodontal disease is best considered as the outcome of an ongoing host-parasite interaction between pathogenic microorganism that have colonized the periodontal pocket and host tissues that resist such bacteria or their products.[2] Many systemic disease and disorders have been impacted as risk indicator or risk factor in periodontal disease. One such example is diabetes mellitus.[3]

Diabetes is a syndrome or a set of syndromes resulting from an absolute or relative insulin deficit.[4] Diabetes mellitus is a complex and a globally evolving chronic health problem faced by the world today. The Indian task force on diabetes care have reported that a crude prevalence rate of 9% in urban and 3% in rural population. In 1993, Löe described periodontal disease as the sixth complication of diabetes, after diabetic nephropathy, neuropathy, retinopathy, vascular disease, and delayed healing.[5] Research has been conducted on the relationship between diabetes and periodontal disease, since the 1960s; these studies reported that there was at least two-fold increase in risk of periodontal disease in diabetics, when compared with healthy controls.[6-8] A meta-analysis of four studies with a total of 3,524 adult patients (>18 years old) showed that diabetic patients have a two-fold higher risk of developing periodontal disease compared to non-diabetics.[9]

Diabetes mellitus has been suggested as a risk factor for periodontal disease and periodontal disease is supposed to increase the severity of diabetes mellitus and complicated metabolic control. Thus, it is proposed to be a dual pathway.[10] Studies reported that clinical periodontal variables were improved by the sole use of mechanical treatment. However, the effects of mechanical treatment alone on metabolic control in diabetes are controversial, with some authors observing no influence on metabolic variables,[11-13] and others reporting an improvement.[14-17]

Studies on the effect of combined mechanical and antibiotic treatment on metabolic control in diabetes demonstrated an improvement in metabolic variables, when local or systemic antibiotics were administered.[1819] There are several possible explanations for this effect. The antibiotic used in these studies was doxycycline, which has both antimicrobial and host-response modifying effects, and a possible non-enzymatic inhibitory effect on glycation.

In this aspect, different studies clearly show that estimation of glycated hemoglobin can be an important and reliable parameter to judge the effective periodontal treatment on the level of glycemic control. Keeping this in mind, it was planned to conduct a study to evaluate the effect of periodontal therapy on type-2 diabetic mellitus patients with chronic periodontitis and systemically healthy patients with chronic periodontitis, by measuring the level of the glycated hemoglobin (HbA1c).

MATERIALS AND METHODS

Present study is a prospective, parallel, comparative, longitudinal clinical study, and carried out for the management of periodontal infection in experimental group with type 2 diabetics and control group with non diabetics.

Selection criteria

The following were the inclusion criteria

Patient's age between 30-70 years,

Presence of type 2 diabetes, criteria for diagnosis of diabetes mellitus are -symptoms of diabetes plus HbA1c≥6.0%, random blood glucose concentration of 200 mg/dl, fasting plasma glucose≥126 mg/dl (Harrison's 15th ed, Principles of Internal Medicine),

Clinical diagnosis of moderate generalized chronicperiodontitis defined by loss of clinical attachment of 4 to 6 mm in all quadrants. Radio-graphically assessed bone loss of 30-50%,

Presence of ≥10 teeth per dental arch, excluding third molars,

No previous periodontal treatment taken,

Signing informed consent, and commitment to post treatment follow-up visits,

No modification in medication for two months, before or during the study.

The following were the exclusion criteria

Presence of systemic disease that could influence the course of periodontal disease or hemoglobin levels in blood,

Intake of anti-inflammatory antibiotics for four weeks before the study,

Current smokers or ex-smokers of <5 years,

Pregnancy or intention to be pregnant during the six months of study.

Sample size

After applying the inclusion and exclusion criteria for the two groups of patients consecutively selected: 15 patients, with type 2 diabetes visiting diabetes out-patient department (OPD), Department of Medicine R.N.T Hospital, having periodontal disease were selected as an experimental group, and 15 patients, with moderate chronic generalized periodontitis came to OPD of Department of Periodontology, Darshan Dental College and Hospital, Udaipur, were selected as a control group.

Study design

After their selection for the study, the patients underwent an initial examination including the following: General medical history, O.P.G. for radiographic assessment of bone loss, determinations of HbA1c and glucose in blood, periodontal examination, and provision of information/instructions on periodontal disease, oral hygiene, and supra-gingival prophylaxis. At the second visit, the conventional treatment indicated for moderate generalized chronic periodontitis was started. Thus, the sessions of scaling and root planing using Gracey curettes under local anesthesia, if required, were started. After the active periodontal treatment, follow-up examinations at three and six months included all elements of the initial examination (determinations of HbA1c and glucose in blood, periodontal examination, provision of information/instructions on periodontal disease and oral hygiene, and supra-gingival prophylaxis), except for the general medical history and radiography.

The following periodontal examinations were assessed in all teeth present, excluding third molars: Plaque control record (O’learys index), the gingival bleeding index of Ainamo and Bay, gingival index (Sillness and Loe), and probing depth.

RESULTS

This study was being conducted on 30 patients; 15 diabetics and 15 non-diabetics, with chronic generalized periodontitis, were enrolled.

Out of 15 diabetic subjects, male were 6 (40%) and female were 9 (60%). Mean age in diabetics were 50.46 years. In non-diabetic subjects, 9 (60%) were male and 6 (40%) were female, with mean age of 40.73 years [Table 1].

Table 1

Demographics of study population shows mean age and % of male and female participated in both the groups

The mean values and standard deviation (SD) of all the parameters (plaque index (PI), bleeding index (BI), gingival index (GI), periodontal pocket depth (PPD), fasting blood sugar level (FBS), and HbA1c) were estimated at baseline, three months, and six months. Multi Variant Analysis of Variance (ANOVA) was used to compare following variables between groups and function of time: HbA1c in blood, glucose in blood, plaque index, bleeding index, gingival index, and periodontal probing depth (diabetic group: [Tables 2 and 3] and non-diabetic group: [Tables 4 and 5]).

Table 2

Clinical and metabolic parameters in diabetic group, at baseline, 3 months, and 6 months in response to conventional periodontal treatment shows mean and standard deviation of all clinical and metabolic parameters in diabetic group

Table 3

Differences in clinical and metabolic parameters in diabetic group, after conventional periodontal treatment shows difference in clinical and metabolic parameter at period of time interval (P value)

Table 4

Clinical and metabolic parameters in non-diabetic group, at baseline, 3 months, and 6 months in response to conventional periodontal treatment shows mean and standard deviation of all clinical and metabolic parameters in non-diabetic group

Table 5

Differences in clinical and metabolic parameters in non-diabetic group, after conventional periodontal treatment shows difference in clinical and metabolic parameter at period of time interval (P value)

Periodontal parameters

Plaque index

The mean plaque index score was 92.93±12.85 at baseline, which declined to 36.86±16.83 and 64.53±16.72 at three months and six months, respectively, after the periodontal therapy in diabetic group, and in non-diabetic group, mean plaque score is 93.46±10.63 at base line, which reduced to 33.60±9.72 and 70.66±17.26 at three months and six months, respectively [Figure 1]. The mean difference was 0.5894. The mean reduction in the plaque index was statistically significant (P<0.05) at all interval.

Figure 1

Mean plaque score at various time intervals as well as comparison between both the groups

Bleeding index

The mean BI was 85.92±13.30 at baseline, which declined to 53.74±14.56 and 54.66±12.10 at three months and six months, respectively, after the periodontal therapy, in diabetic group. In non-diabetic group, the BI which was 86.66±13.54, from baseline, reduced to 50.50±10.23 at three months and 57.24±8.24 at six months [Figure 2]. Mean reduction in BI at baseline to three months and six months, after periodontal therapy, was statistically significant (P<0.05) in both the groups.

Figure 2

Mean bleeding index score at various time intervals as well as comparison between both the groups

Gingival index

Following the treatment, the GI dropped from 1.81±0.61 at baseline to 1.05±0.30 and 1.22±0.29 after three months and six months, respectively, in diabetic group, and the reduction in GI from 1.93±0.36 at baseline to 1.21±0.25 and 1.26±0.20 after three months and six months, respectively, in non-diabetic group [Figure 3]. Reduction in the GI was statistically significant (P<0.05) in both the groups, at baseline to three months and baseline to six months.

Figure 3

Mean gingival index score at various time intervals as well as comparison between both the groups

Probing pocket depth

Following the non surgical periodontal treatment, PD decreased from 3.16±0.65 baseline to 2.72±0.39 and 1.67±0.43 after three months and six months, respectively, in diabetic group. While in non-diabetic group, readings were 3.04±0.64 at baseline, and 2.41±0.41 and 2.03±0.45 after three months and six months, respectively [Figure 4]. Reduction in PD was statistically significant (P<0.05) in both the groups, at baseline to three months and baseline to six months, while mean reduction in both the groups at three months to six months of interval was not statistically significant (P>0.05).

Figure 4

Mean reduction in pocket probing depth at various time interval as well as comparison between both the groups

Metabolic parameters

Fasting blood sugar level

The mean FBS was 159.53±32.53 at baseline, which reduced to 140.50±22.83 at three months and 126.39±16.04 at six months, in diabetic group [Figure 5]. Mean reduction of FBS was statistically significant (P<0.05) in baseline to six months of interval only.

Figure 5

Mean fasting blood sugar levels at various time intervals as well as comparison between both the groups

Glycated hemoglobin

The mean HbA1c value at baseline was 8.18±1.56, which reduced to 7.20±1.37 and 6.73±1.07 at three months and six months, respectively, after the periodontal therapy, in diabetic group [Figure 6]. The mean reduction in HbA1c values from baseline to six months after the periodontal therapy which was statistically significant (P<0.05), while HbA1c reduce between baseline to three months and three months to six months of interval, but it was not statistically significant (P<0.05).

Figure 6

Mean HbA1c level at various time intervals as well as comparison between both the groups

DISCUSSION

Periodontitis is a complex multi-factorial disease. Similarly, diabetes mellitus is a complex metabolic syndrome. It is the complexity of both of these processes which has contributed to the controversies and their probable interrelationship in the literature.[20]

Our aim of present study was that after control over periodontal infection, to evaluate metabolic control of diabetes by means of improvement in blood HbA1c level after three and six months. Primary methods used to diagnose diabetes mellitus and monitor blood glucose levels have been fasting blood glucose and glucose assay has been developed which does not require fasting, does not rely on patient compliance and gives indication of blood glucose level over an extended period of time past three to four months, is HbA1c assay.

This HbA1c assay is of interest, as it offers advantages over traditional blood glucose monitoring methods. Numerous proteins in the body are capable of being glycated. Glycated hemoglobin is formed continuously in erythrocytes as a product of the non-enzymatic reaction between the hemoglobin protein, which carries oxygen molecules and glucose. Binding of glucose to hemoglobin is highly stable; thus, hemoglobin remains glycated for the life-span of erythrocyte approximately 123±23 days.[21]

There are principally three methods of HbA1c examination: Flow cytometry, high performance liquid chromatography, and turbidimetric inhibition immunoassay (TINIA). The method used in this study is by TINIA by COBAS® auto analyzer.

In agreement with study of Ricardo Faria-Almeida, Ana Navarro, and Antonio Bascones (2006), significant improvement was seen in plaque control throughout the present study.[22] Also, diabetic group plaque score reduction [Table 3] from baseline to three months, from three to six months, and from baseline to six months, from all examinations P<0.00, was suggestive of highly significant improvement. In non-diabetic group, plaque score reduction, [Table 5] from all examinations P<0.00, was suggestive of highly significant improvement.

Significant changes (P<0.05) in bleeding index and gingival index were also evident in the study in both the groups [Tables 3 and 5]. Other studies by Christgau et al.[23] Patricia et al.[24] Ricardo et al.,[22] and Kiran et al.[25] also showed similar results.

Statistically significant differences (P<0.05) in mean probing depth were found between the two groups (diabetic and control groups), with better outcomes for the control group. However, both groups showed significant improvements (P<0.05) at baseline to three months and baseline to six months [Tables 3 and 5]. Probing depth observed in our study are in agreement with Grossi et al.[26] who, using doxycycline, showed reductions of 17% at three months, 23% at six months, in type 2 diabetic patients. The reduction in probing depth observed in study of Débora C. Rodrigues[27] were 25% after three months.

The change in FBS from baseline to three months is 19.03±9.71 mg/ml (P>0.05), 3 months to 6 months is 14.10±6.83 mg/ml (P>0.05), and baseline to six months is 33.14±16.54 mg/ml (P<0.05), which shows that values of FBS couldn’t reach up to statistically significant improvement in all examinations. FBS is highly variable, with transient fluctuation in blood glucose level at the time of sampling. It couldn’t be considered for long term metabolic control.

In the present study, reduction in HbA1c level, in diabetic group [Tables 2 and 3], was from baseline to three months was 12%, from three to six months was 6.5%, and from baseline to six months was 18.5%. These results were suggestive of non-surgical periodontal therapy that lead to the reduction in HbA1c levels, especially in patients with an elevated degree of diabetes mellitus severity and periodontal disease. Thus, it is possible that treatment of chronic periodontitis improve glycemic status of diabetics. Reduction in HbA1c levels in the present study confirms results of prior studies as described as follows: In the study of Débora C. Rodrigues,[17] both the groups showed reductions in HbA1c levels. The change in HbA1c levels was 4% in G1 (one stage full mouth scaling and root planing plus amoxicillin/clavulanic acid, 875 mg) and 11% in G2 (one stage full mouth scaling and root planing alone), with a statistically significant difference between groups. Stewart et al.[28] in a retrospective study, evaluated patients who received scaling and root planing without antibiotics; after 10 months, glycated hemoglobin examinations were performed, and revealed an average reduction of 17% from baseline HbA1c levels. HbA1c levels, in non-diabetic control group [Tables 4 and 5], was at baseline, 5.33±0.45, after treatment for three months, it was at 5.21±0.37, after treatment for six months, it was at 5.26±0.39. This also shows non-diabetic status of control group in comparison with diabetic group, throughout the study.

Hence, there is a two-way relationship between diabetes mellitus and periodontitis, with the former producing a greater severity of periodontal disease and the latter compromising blood glucose control in diabetic patients. Treatment of periodontitis in diabetic patients would lead to a reduction in the soluble mediators responsible for periodontal tissue destruction and would lessen the insulin resistance of the tissues. The findings of this study showed that effective periodontal treatment resulted in lower glycemic levels, which can be measured with the help of HbA1c assay – a reliable long term marker of glycemic control, and in the reduction of clinical parameters of periodontal infection, confirming the existing interrelationship between diabetes mellitus type-2 and periodontitis. Therefore, periodontal treatment should be included in diabetes preventive measures.

CONCLUSIONS

Both patient groups improved clinically, after basic non-surgical periodontal treatment,

A statistically significant improvement in clinical variables was found in both the groups between baseline to three and six months (P<0.05),

The control group showed a greater reduction in probing depth, as a result of the periodontal treatment,

The diabetic patients showed statistically significant improvement in their metabolic control from baseline to six months, as measured by HbA1c levels (P<0.05), as a result of the conventional periodontal therapy.

Clinical implications

The periodontist and physician must work together as a team to achieve rigorous metabolic control of diabetes in their patients.