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Year : 2013 | Volume : 1 | Issue : 1 | Page : 17 - 19  


Original Articles
Role of ADA in immunological disorders - Diabetes mellitus and Thyroid dysfunction

Vishnu Madhuri1, V. Sampath Kumar2, Shruti Mohanty3

1 Tutor and 3Professor & Head, Dept. of Biochemistrty, Kamineni Institute of Medical Sciences, Narketpally, Nalgonda(Dist), 2 Associate professor, Dept. of Biochemistry, Malla Reddy Institute of Medical Sciences, Jeedimetla, Hyderabad

Abstract:

Background: Adenosine deaminase (ADA) is a cytosolic enzyme, which participates in development and maintenance of the immune system. Diabetic patients have a higher prevalence of thyroid disorders compared to the normal population because patients with one organ-specific autoimmune disease are at risk of developing other autoimmune disorders. Methods: A total number of one hundred subjects were divided into four groups consist of group A. Type II Diabetic patients, group B. Hypothyroid patients, group C. Hyperthyroid patients and group D. Healthy controls of either sex between age group of 30-70 years. The following biochemical parameters were estimated for all the groups. Fasting plasma glucose, Serum T3, T4, TSH and Adenosine deaminase.

Results: Mean serum ADA levels were raised in diabetic and hypothyroid patients when compared to that in controls and  which was statistically significant (p<0.0001). Unlike hypothyroid, serum ADA levels in hyperthyroid patients were within normal limits. Conclusion: Increase in serum ADA levels in the diabetic and the hypothyroid patients when compared to controls, are suggestive of an association with a common immunological disturbance. Increase in serum TSH levels in diabetes patient increase in fasting blood sugar level in hypothyroid patients, when compared to healthy controls is suggestive of diabetic patients probably suffering from subclinical hypothyroidism and patients with hypothyroidism suffering from impaired glucose metabolism.

Keywords: Adenosine deaminase, Diabetes mellitus, Hyperthyroidism, Hypothyroidism.

 

Corresponding Author: Dr. Sampath kumar, Associate Professor, Dept. of Biochemistrty, Mallareddy Institute of Medical Sciences, Jeedimetla, Hyderabad, India.

Email: sampath.surya76@gmail.com

 

Introduction  

Adenosine deaminase (ADA EC 3.5.4.4) is a cytosolic enzyme, primary function in humans is the development and maintenance of the immune system, which participates in the purine metabolism. [1] Immunological disturbances in diabetic individuals have an association with cell mediated responses and inappropriate T-lymphocyte function, which is vital in this pathogenic condition and has a link with insulin defect. Previously, adenosine deaminase has been reported to be a marker for insulin function. But its connection with the immune system was not yet established in Type II diabetic subjects. [ 2 ]

Studies have revealed that 14 - 32% of Type II diabetic patients develop auto antibodies to islet cell antigens within the first 5 years of diagnosis. These individuals represent a special subset of type II diabetics as seen by their deficiency of insulin secretion, elevated frequency of certain HLA genes, elevated frequency of thyroid or gastric auto antibodies and high risk for requiring insulin treatment. [3] The clinical association of autoimmune diseases has shown that among patients in southern India, autoimmune diseases were diagnosed in 1.68% of persons with diabetes mellitus (147/15,523). Diabetes mellitus was diagnosed in 2.3% of persons with hypothyroidism (33/1435) and in 4.35% with thyrotoxicosis (15/345). [4] Diabetic patients have a higher prevalence of thyroid disorders compared to the normal population because patients with one organ-specific autoimmune disease are at risk of developing other autoimmune disorders. [5] Hypothyroidism is the most common thyroid disorder in the adult population. It is usually autoimmune in origin. By contrast, hyperthyroidism is much less common; with a female-to-male ratio of 9:1. [6]

The presence of thyroid dysfunction may affect diabetes control. Hyperthyroidism is typically associated with worsening glycemic control and increased insulin requirements. There is underlying increased hepatic gluconeogenesis, rapid gastrointestinal glucose absorption, and probably increased insulin resistance. [5] The present study is carried out to make an attempt on the metabolic and immunogenetic aspects of the relationship between diabetes mellitus and thyroid disease and also to assess thyroid function in diabetes and glycemic status in thyroid dysfunction.          

MATERIALS AND METHODS

A total number of one hundred subjects, age group of between 30 - 70 years divided into four groups, (Group A) 25 diagnosed as Diabetic patients, 25 patients diagnosed as Hypothyroidism (Group B) and 25 patients diagnosed as Hyperthyroidism (Group C) of either sex, who were attending medical OPD of KIMS hospital for treatment and follow up. Group D consist of 25 apparently healthy age and sex matched controls with no known systemic disorders were included in this study.

Inclusion criteria: The patients those who were diagnosed already as hypothyroidism, hyperthyroidism and diabetes mellitus on treatment with no known complications.

Exclusion criteria: Patients, those who are suffering from malignancy, tuberculosis, coronary artery disease, renal disease and subjects on drugs interfering with glucose and thyroid hormone metabolism.

Sample collection and methods of estimation of parameters: After obtaining approval from Institutional ethical committee informed consent was taken from all the subjects. 5ml of venous sample was collected in two separate sterile, clean and dry sample collecting bottles and centrifuged at 3000 rpm for 10 minutes for the preparation of plasma and serum for the estimation of following biochemical parameters. Plasma fasting blood glucose was determined by GOD-POD method, Serum T3, T4 and TSH by ELISA method and Serum adenosine deaminase (ADA) by Guisti and Galanti method.

 

RESULTS

In the present study, of the 25 diabetic patients 14 were males and 11 females. It was noted that there were more male diabetic patients in our study involving the local population. However, there were 12 females and only 4 males in 30-50 years age group and 6 females and 3 males in 50-70 years age group of the 25 hypothyroid patients suggesting that hypothyroidism is more common in females in the local population. Of the 25 hyperthyroid patients 21 patients were in the age group of 30-50 years, of which 11 were females and 10 males suggesting 84% of the hyperthyroid patients belong to 30-50 years age group in the present study.

 

Table 1: Serum ADA levels in Diabetics (Group A),

Hypo thyroidism (groupB), Hyper thyroidism(group C) and Controls (Group D)

 

Group

    ADA (U/L)

P value

  Mean + SD

Diabetes   (A)        

28.78 + 6.61

     <     0.0001

Hypothyroidism (B)

27.83 + 6.64

     <     0.0001

Hyperthyroidism(C)

10.87 + 2.60

0.0461

Controls(D)

12.19 + 2.22

 

 

Serum ADA levels in Diabetics (Group A), Hypothyroidism (group B), Hyperthyroidism (group C) and Controls (Group D) are shown in the table 1.

The serum ADA in diabetics was increased (28.78 + 6.61) compared to controls (12.19 + 2.22) which was statistically highly significant (p<0.0001).On comparing serum ADA in hypothyroid patients it was observed that serum ADA was elevated (27.83 + 6.64) when compared to healthy controls (12.19 + 2.22) and was statistically highly significant (p<0.0001).     Unlike hypothyroid patients the serum levels of ADA in hyperthyroid patients (10.87 + 2.60) was within the normal range as with the control group (12.19 + 2.22) without any statistical significance.

Thyroid profile in diabetic patients as shown in the table 2

In our study we observed that the TSH levels were increased in diabetic patients (7.56 + 8.4) when compared to controls (2.75 + 2.00) which were statistically significant. However serum T3 andT4 levels were within the normal range.

 

Table 2: Thyroid profile in diabetic patients and controls

Group

TSH

T3

T4

(normal:                                 0.39-6.16µIU/ml)

(normal:                     0.52-1.85ng/ml)

(normal:                 male:4.4-10.8µg/dl, female:4.8-11.6µg/dl)

  Diabetics   (n=25)

       7.56 + 8.4

       0.93 + 0.44

       6.87 + 2.41                              

    Controls   (n=25)

       2.75 + 2.00

       1.00 + 0.35

       7.40 + 2.05

 

Blood glucose in thyroid patients are shown in table no: III

In our study we observed that fasting blood glucose levels were markedly increased in hypothyroid patients (121.17+ 38.95) when compared to controls (87.64 + 16.39) which were statistically significant. However the fasting serum blood glucose was within the normal range in the hyperthyroid patients.

 

Table 3: Blood glucose in thyroid patients

 

Parameter

Controls

Hypothyroidism

Hyperthyroidism

FBS (mg/dl)

87.64

121.17

97.21

(mean + SD)

+ 16.39

+ 8.95

+ 27.79

 

 Table 4: Comparison of serum ADA in diabetic patients.

 

Author

Serum ADA (U/L)               Mean +   SD

         P value

  M Shiva Prakash et al

37.2 + 9.29

P < 0.0001

  Present Study

28.78 + 6.61

P < 0.0001

Table 5: Incidence of abnormal thyroid hormone levels in diabetic patients

Author

       Number of diabetic patients

    Hypothyroidism

  Hyperthyroidism

C.E.J.Udiong et al

161

26.60%

19.90%

Present Study

25

20%

20%

 

DISCUSSION

A variety of thyroid abnormalities may coexist and interact with diabetes mellitus. The hypo and hyper functioning thyroid gland influences carbohydrate metabolism at the levels of pancreatic islets and glucose utilizing target tissues, posing important therapeutic and diagnostic questions. Moreover, thyroidal and islet cells are affected by diseases that are clinically and genetically associated, and where parallel autoimmune pathogenesis is very highly suspected. [7] In this study serum ADA was estimated to assess the role of ADA as an immunological marker enzyme for etiopathology of diabetes and thyroid disorders.

Comparison of serum ADA in diabetic patients is shown in table-IV:

The serum ADA values in this study showed statistically highly significant (P < 0.0001) difference between cases and controls. This is in accordance with the study of M. Shiva Prakash et al [6] who suggested that serum ADA were increased in subjects who were diabetic (p < 0.0001). An increase in ADA activity in type 2 diabetic patients has been reported, While the mechanism that increases serum and tissue ADA activity is not well known, with higher ADA activity in insulin-sensitive tissues, the level of adenosine, which increases glucose uptake into cells, will be reduced. Thus, if ADA activity is suppressed, insulin sensitivity may be improved, and cellular proliferation, inflammation, and T-cell activity, all of which are associated with the pathophysiology of insulin resistance, can also be affected. Therefore, insulin resistance may have an important relationship with ADA activity. However, it is difficult to conclude whether changes in ADA activity are the cause or result of actual insulin. [7] However a study conducted by Ogbu I.S.I et al [8] showed no significant difference between cases and controls regarding serum ADA. In our study, serum ADA levels were raised in diabetic patients when compared to that in controls (p<0.0001). This could be due to autoimmune destruction of pancreatic β cells resulting in insulin deficiency or resistance to insulin action.

In the present study serum ADA was compared in patients with hypothyroid, hyperthyroid and in healthy controls. It was observed that there is an increase in serum ADA levels in hypothyroidism (27.83 +/- 6.64) when compared to healthy controls which was statistically significant (p<0.0001) suggesting the role of autoimmunity. Unlike hypothyroid patients serum ADA levels in hyperthyroid patients were within normal limits (10.87 +/- 2.60). Litvinenko [9] observed that there is increase in ADA activity up to 72% in hypothyroidism. Mitchell E. Geffner et al [10] reported that combined immunodeficiency secondary to adenosine deaminase deficiency developed in thyroid failure of probable autoimmune origin manifested by linear growth deceleration, marked bone-age delay and myxoedema in children. The diagnosis of auto immune thyroid disease was suggested by the presence of anti thyroglobulin antibodies in the serum and by decreased, patchy uptake of iodine123 on a thyroid scan.    

Incidence of abnormal thyroid hormone levels in diabetic patients are depicted in Table no:V    In a study conducted by C.E.J.Udiong et al, [11] out of 161 diabetic patients 26.6% were hypothyroid and 19.9% were hyperthyroid patients. In the present study, out of 25 diabetic patients, 5 had increased TSH and normal T3 and T4 suggesting subclinical hypothyroidism. The present study depicted that there was an increase in fasting blood glucose levels (121.17 + 38.95) in hypothyroid patients unlike in hyperthyroid patients (97.21+ 27.79) when compared to controls (87.64 + 16.39). This is suggestive of impaired tolerance by the hypothyroid patients. Though there could be some metabolic cause for increased blood glucose levels in hypothyroid patients but immunological disturbances cannot be ruled out because of increased ADA levels, since diabetes mellitus and thyroid disorders have a common autoimmune etiology hypothyroid patients having increased blood sugar could be due to disturbance in the immunity.

A total number of one hundred subjects were divided into four groups of 25 in each. This number is not enough to draw the conclusion but it may acts as a guide towards some scientific opinion. This is the limitation of our study.

CONCLUSION

In present study we observed that hypothyroid and diabetic patients had increased blood ADA levels suggestive of a common autoimmune pathogenesis. Serum ADA estimation can be used as an immunological marker enzyme in both diabetes mellitus and thyroid disorders. Therefore patients diagnosed as diabetics must also undergo thyroid profile to exclude thyroid disorders. Likewise, thyroid dysfunction patients should monitor blood glucose to exclude impaired glucose metabolism.

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          Changes in Adenosine Deaminase Activity in    Patients with Type 2 Diabetes Mellitus and Effect

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Source of support: Nil.

Conflict of interest: Not Declared

 

 

 

 

 





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