Immunological Study of Type 2 Diabetic Patients with Periodontal Disease

Immunological Study of Type 2 Diabetic Patients with Periodontal Disease

1, Khalid Hassan Khan 2. Shahab Adil 3. Bilal Hassan Khan 4. Zafarullah Khan
5. Abdul Hafeez Sheikh

1. House Officer, Khyber College of Dentistry, Peshawar 2. Asstt. Prof., Khyber College of Dentistry, Peshawar
3. Student Final year, Bacha Khan Medical College, Mardan 4. Consultant Endocrinology, MoH, Saudi Arabia
5. OMF Surgeon, MoH, Saudi Arabia

ABSTRACT

Objective: To evaluate the IgA, IgG and IgM levels in the serum samples of type 2 diabetic and Periodontal patients of the Peshawar area having different life style set up.

Study Design: Case control study

Place and duration of Study: This study was carried out on subjects who fulfilled our criteria and agreed to participate in the study were included. They were residents of Peshawar area and visited OPDs of Khyber College of dentistry, Peshawar during July, 2012 to June, 2013.

Patients and Methods: Among 120 participants, 30 were healthy, 30 were with periodontitis, 30 had diabetes and the remaining 30 had both diabetes and periodontitis. All of them had at least 20 natural teeth. Diabetic patients had the disease history minimum of five years while the periodontal patients had clinically confirmed the disease. Blood samples were collected from each of the participant and immunoglobulins A,  G and M were measured. The observed data were analyzed accordingly through standard statistical methods.

Results: Male patients were found more as compared to females (ratio 1: 0.87) in the two diseases. The age range was 35 to 54 years with the mean 44+5. As per HBA1C results; 40 % had good control of diabetes, 26 % moderate while in 34 % control was poor.

Immunoglobulin A and G levels were found significantly higher (p < 0.05) in the three disease groups as compared to control group. Whereas the concentration of IgM was not changed by the said diseases.

Besides, the gender has no influence on the levels of the three immunoglobulins. The IgG levels increased with the increase in severity of the Periodontitis disease. While IgA showed slight decrease with the increase in clinical grades of the Diabetes disease.

Conclusion: The result of the current study indicates the role of humoral immune response in the two  mentioned diseases. The higher levels of immunoglobins particularly IgA and IgG might be  due to protective mechanism against the weak immune response and the increased bacterial challenge in diabetes and periodontitis.

Key Words: Immunoglobulins, Periodontitis, Diabetes Mellitus.


 

INTRODUCTION

Diabetes mellitus is a metabolic disease and a major health problem throughout the world.  Its prevalence is increasing not only due to genetic factors but also due to stress and changing lifestyle modification. The number of estimated cases of diabetes increased from 30 million in 1985 to 135 million in 1995 and is projected to increase to 366 million by the year 20301. About 1.5 million cases of diabetes with age above 20 were diagnosed in a single year, 20052.  Only in the United States, about 18 million people are suffering from this disease3. The prevalence of diabetes mellitus in our country is ranked 8th in the world1 and its figure is 1.49% in the Khyber PukhtoonKhwa Province4.

In diabetes, the body metabolism fails to utilize glucose for the production of energy and hence its levels increase in the blood. Besides, glucose levels in the saliva also increase, which act as a fuel substrate for the bacteria in the mouth and hence favor the growth of pathogens in periodontal pockets.  In addition, diabetic patients develop dry mouth a condition that predisposes to infection. Bacteria and infection in the mouth are a risk factor for initiation and progression of periodontitis. An early study described that people with poor blood glucose control tend to develop periodontal disease more severely and more frequently than people with good control of their diabetes5. The dental clinicians also highlighted that Periodontitis is the most widely noted manifestation of Diabetes mellitus6.

Both diabetes mellitus and periodontal disease are contributing to the dysfunction in the immune system. Besides, self mediated immunity is reported to play a protective or aggressive role in the pathogenesis of periodontal disease7. Altered immune function in diabetic patients with periodontitis have been reported by several studies7,8. They used salivary immunoglobulins as parameters to assess the status of humoral immunity. Another scientist investigated immunoglobulins in the gingival tissue of diabetic patients with periodontitis9. But there are no such data regarding  serum samples, particularly of our population; having different nutrition, lifestyle, environment and socioeconomic condition. The present study was, therefore, undertaken to evaluate the immune profile (IgA, IgG and IgM) in serum among patients  and control of this particular area (Peshawar).

MATERIALS AND METHODS

One hundred and twenty patients who visited Khyber College of dentistry, Peshawar, for treatment during July, 2012 to June, 2013, fulfilled our criteria and agreed for this case control study were investigated. The subjects were divided into four groups as described in table-1. Information regarding age, sex, education level, occupation, dietary history,  family income and previous laboratory investigation were also collected from each of them.

The age range of all volunteers of the four groups was between 35 to 54 years. All of them had at least 20 permanent teeth in the mouth and without caries. Diabetic patients had history of the disease at least for the past 05 years. Periodontal patients had clinical attachment loss ≥ 2mm and pocket depth ≥ 4 mm in each quadrant of their mouth. Patients having severe respiratory tract infections, hypertension, liver disease, coexistent lesions, rheumatoid factor above 500 iu/ml, Albumin above 07 g/dl, allergy or autoimmune disorders  were excluded from the study.

Participants were explained the objectives of the study and assured of the confidentiality.  Informed consent was obtained from each subject enrolled in the study. The work was approved from the local ethical research committee of the institute. Five  ml fasting venous blood was collected from all the patients and serum was separated. The specimens were stored at -200C till immunoglobulin estimations was carried out.

Immunoglobulins A, G and M were quantitatively determined with the help of  diagnostic kits as used for instrument, Cobas Integra 400 Roche company10. The normal reference ranges as described by this method are 0.7 to 4.0 g/l for IgA, 7.0 to 16.0 for IgG and 0.4 to 2.3 g/l for IgM. The observed data was tabulated. Karl Pearson correlation test was used to correlate the association between various parameters.  Comparison of different parameters between control and disease groups was done by t-test. A p-value less than 0.05 were considered statistically significant.

RESULTS

Sixty three (52.5 %) males and 57 (47.5 %) females were investigated in the present study. Their education levels are described in figure-1. Twenty two patients had diabetes for the past 20 years, 24 for the past 10 years, whereas 14 patients had duration of the disease in between 05 to 09 years. Figure-2 is regarding control of the disease( as per HbA1C result)  among diabetic patients.

The reasons to visit the dentist are described in table-2. Besides, 58 % of the participants mentioned that they had visited the dental hospital for the first time. The most common reasons mentioned for the hesitation of no dental visits was viral transmission due dental instruments, unpleasant/time consuming dental procedure and the expensive treatment.

The average concentrations of the three immunoglobulins  are described in table-3. Males and females had the same pattern of the three immunoglobulins among all the groups. The IgA and IgG levels were found significantly higher (p < 0.05) in the serum of the three disease groups as compared to control group. Whereas the concentration of IgM was not changed and showed almost similar patterns in  all the four groups.  Besides, the IgG levels increased with the severity of the periodontal disease. While IgA showed slight decrease with the increase in clinical grades of the diabetes disease. Both these immunoglobulins A and G decreased in all subjects with the progress of the age.

Table No.1:  Distribution of subjects by sex.

Subject

Males

%age

Females

%age

Healthy

15

50.0%

15

50.0%

Periodontitis

17

56.7%

13

43.3%

Diabetes

16

53.3%

14

46.6%

Diabetes with Periodontitis

15

50.0%

15

50.0%

Total

63

52.5%

57

47.5%

Table No.2: Reasons to visit the dentist among the total.

Reason

Number of subjects

Percent

Tooth pain

36

30.0 %

Mouth Infection

24

20.0 %

Bleeding with a brush

22

18.3 %

Extraction

21

17.5 %

Periodontal problem

17

14.2 %

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Figure No.1: Education Levels of the  Participants

Table No.3:  Mean Immunoglobulin Levels among Participants.

Group

IgA (g/l)

IgG (g/d)

IgM (g/l)

Healthy

2.3

10.21

1.05

Periodontitis

4.3

15.93

0.96

Diabetes

4.8

14.52

0.87

Diabetes with Periodontitis

5.3

16.34

0.81

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Figure No.2: Control of disease among diabetic patients

DISCUSSION

The humoral immune response plays an important role in the two diseases i.e. diabetes and periodontitis. We also found altered immunoglobulin levels in the mentioned diseases. The  literature review highlighted that periodontitis is a frequent complication of diabetes, and diabetic subjects often exhibit decreased immune response and more complications9. Besides, like our study, other study also documented that the oral complications of diabetes increase with the age and poor control of the disease11.

Both males and females exhibited a similar pattern of immunoglobulins in the controls as well as in the diseased subjects. Similar findings were observed earlier7. The level of serum IgA and IgG in the diseased group was found elevated. Another study also showed increased levels of IgA and IgG in the diseased group as compared to the healthy subjects9.  The most probable reason for this elevation might be the tissue alterations in the same disease and increased antibody production as required for neutralization of toxins. Some scientists demonstrated that IgA and IgG play a protective role in the pathogenesis of periodontal disease12. While Vaziri and his coworkers reported no significant difference in the salivary IgA levels between control and diabetic subjects13.

The IgG levels increased with the increase in severity of the Periodontitis disease. The reason might be that more antibodies are needed for chronic infection. Other scientists also agreed with such findings9.  While IgA showed  slight decrease with the increase in clinical grades of the diabetes disease. This may be either due to the weak response of the diabetes or special homeostatic mechanism of the body. The literature review is not clear regarding this point. Moreover, immunoglobulins A and G decreased with the progress of the age in the present study. This is in agreement with normal physiological function.

The IgM level was not changed in the diseased group. These findings are in accordance with the previous studies7,9. The possible explanation may be that local synthesis of immunoglobulin M does not occur in the periodontitis and hence there is no diffusion of IgM unlike IgA and IgG in the blood stream from a local source.  In addition, the synthesis of the same immunoglobulin is slow in diabetes and increase usually in the autoimmune diseases and viral infections14. Hence the information regarding the immune response in the two diseases is contradictory and has not been studied extensively in our country. Therefore, it should be given special attention  and further study comprising of large sample size including other parts of the country has to be designed so as to clarify all these observations.

CONCLUSION

The result of the current study indicates the role of humoral immune response in the two  mentioned diseases. The higher levels of immunoglobins particularly IgA and IgG might be  due to protective mechanism against the weak immune response and the increased bacterial challenge in diabetes and periodontitis.

REFERENCES

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3.       Barcelo A, Rajpathak S. Incidence and prevalence of diabetes mellitus in the Americas. Rev Panam Salud Publica 2001; 10: 300–8.

4.       Khan A and Sandbar M. Role of diet, nutrients, spices and natural products in diabetes mellitus. Pak J Nutri 2003; 2(1): 1-12.

5.       Muller LM, Gorter KJ, Hak E, et al. Increased Risk of Common Infections in Patients with Type 1 and Type 2 Diabetes Mellitus. Clin Inf Dis 2005; 41: 281-8.

6.       Chandna S, Bathla M, Maadan V. Diabetes Mellitus-a risk factor for periodontal disease. Int J Family Prac 2009; 9 (1):4-8.

7.       Kinane D, Laffin DF. Clinical, Pathological and immunological aspects of periodontal disease. Acta Odontologica Scandinavica 2001;59(3):154-60.

8.       Southerland JH, offenbacher S. Diabetes and periodontal infection: making the connection. J Clin Diabetes 2005; 23 (4): 171-8.

9.       Anil S. immunoglobulin concentration in gingival tissue of type 2 diabetic patients with periodontitis. Ind J Dent Res 2006;17(4): 151-154.

10.    Brostoff J, Scadding GH, Male D, Roit IM. Clinical immunology, London: Gower Medical Publishing;1991.p.1-8.

11.    Alnzha MM, Almatoug MA, Alhathi SS. Diabetes Mellitus in Saudi Arabia. Saudi Med J 2004;25 (11): 1603-10.

12.    Yen-Tung A Teng. The role of acquired immunity and periodontal disease progression. J Oral Biol and Med 2003;14(4): 237-52.

13.    Vaziri PB, Vahidi M. Evaluation of salivary glucose, IgA and flow rate in diabetic patients: A case control study. J Dent 2010;7(10):13-18.

14.    Dispenzieri A Gertz MA, Kyle RA. Retrospective cohort study of 148 patients with polyclonal gammopathy. Mayo Clin Proc 2001; 76: 476-87.

 

Address for Corresponding Author:

Dr. Khalid Hassan Khan

House Officer,
Khyber College of Dentistry,
Peshawar.

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