Introduction
Diabetes mellitus is a chronic metabolic disorder virtually affecting every organ system in the human body.1 HbA1C is regarded as the gold standard for assessing glycemic control in diabetic patients.2 Individuals with DM have three times the risk of developing TB and there are now more individuals with TB-DM co-morbidity than TB-HIV co-infection.3 Tuberculosis has been a major cause of suffering and death since times of immemorial.4 India has the largest number of TB cases estimated globally to be 2 million per annum and accounts for more than 60 million people with type 2 diabetes.5 After Introduction of Revised national tuberculosis control programme RNTCP there is significant improvements in case detection and control of TB disease, but tuberculosis is complicating diabetes.6 Another important challenge is the growing body of evidence suggesting diabetes as a risk factor for new as well as reactivated old TB cases.7 As a protocol those patients with tuberculoses having diabetes should kept on insulin to achieve glycemic control and good TB treatment outcome. But practically majority of these patients are kept on oral hypoglycemic agents (OHA) alone. This adversely affects tuberculosis treatment outcome. There is strong interaction between OHA’s and anti tuberculosis drugs leading to worsening of glycemic control.8 Poor glycemic control results in higher levels of HbA1c. On careful observation those patients kept on insulin alone with DOTS recovered fast from TB infection by showing early sputum conversion and achieved glycemic control.9 These patients showed lower level of HbA1c as compared with other two groups. This study aims at influence of glycemic control on treatment outcomes in patients with type 2 diabetes mellitus with various forms of tuberculoses.
Materials and Methods
The present study comprises patients with tuberculosis and known diabetic state registered under revised national tuberculosis control programme (RNTCP) in Dept of Pulmonology, PESIMSR, Kuppam, Chittoor district, Andhra Pradesh. Adult aged 30yrs to 80 yrs of both genders were included. Total 60 samples were tested among those 20 were OHA alone patients (Group I), 20 were OHA plus Insulin (Group II) and 20 were insulin alone (Group III) samples were analyzed at clinical Biochemistry lab PESIMSR, Kuppam. The patients with end stage complications of DM such as proliferative retinopathy and nephropathy and with history suggestive of bleeding diathesis or fits with creatinine levels ≥2 mg/dl were excluded from study. 5ml of blood was collected from the patients from the cubital vein under aseptic precautionary measures with 5ml syringe out of this 2ml was collected in EDTA tube for estimation of HbA1C. Remaining 3ml was collected in clot activator tube for blood glucose estimation. Measurement of HbA1C done by fully automatic Bio-Rad D10 - HbA1c Analyzer. Blood glucose levels were estimated by auto analyser VITROS 250.
Statistical Analysis and Results
Statistical data calculated by using SPSS software, analysis of variance (ANOVA) has been used to find the significance of study parameters between three or more groups of patient (Table 1). Post hoc test has been employed to find the pair wise significance (Table 2). A P value <0.05 was considered as significant.
Table 1
Comparison of study variables in three groups by one-way ANOVA
|
Study variables |
Group I |
Group II |
Group III |
p value |
|
HbA1C |
11.21 ± 1.08 |
8.92 ± 0.38 |
6.91 ± 0.57 |
<0.001** |
|
Random blood glucose |
321.85 ± 85.53 |
251.4 ± 97.05 |
161 ± 18.71 |
<0.001** |
Table 2
Pair wise comparison in three groups by multiple comparison post-hoc test
|
Study variables |
Group I vs Group II |
Group I vs Group III |
Group II vs Group III |
|
HbA1C |
<0.001** |
<0.001** |
<0.001** |
|
RBS |
<0.01* |
<0.001** |
<0.001** |
The Table 1, Table 2 and Figure 1, Figure 2 shows that there was significant increased HbA1C and blood glucose levels in group I patients compared with other two groups. The mean levels of HbA1C and blood glucose in group III were 6.91 ± 0.57 and 161.2 ± 18.71 and group II the mean levels of HbA1C and blood glucose were 8.92 ± 0.471 and 215 ± 97.05. In group I the mean levels of HbA1C and blood glucose were 11.21 ± 1.08 and 321.85 ± 85.53. The level was significantly increased (p<0.001) in the group I as compared with group II and group III people.
Discussion
Glycemic status should be strictly watched while diabetic patients kept on DOTS. HbA1c is considered to be a contributory factor to tissue hypoxia by increasing the affinity of hemoglobin-oxygen, while low tissue oxygen concentration is detrimental and causes oxidative stress.10 It has come to light that oxidative stress plays a crucial role in the activation and anti-TB action of isoniazid.11, 12 Rifampicin increases the hepatic metabolism of all sulphonylurea derivatives, the most widely used class of oral diabetes drugs worldwide. This effect on sulphonylurea derivatives has great inter-individual variation, which makes dose adjustments difficult and increases a patient’s risk of hyperglycaemia or hypoglycaemia. Inter-individual variation in the induction of the metabolism of diabetes drugs makes dose adjustment difficult when rifampicin treatment is interrupted or stopped; the same is true for most other oral antidiabetes drugs.13, 14 Then the oral hypoglycemic agents are rapidly eliminated. Isoniazid antagonizes the action of sulphonylureas and worsens glycemic control.15 In some situations, isoniazid decreases the metabolism of oral antiglycemic agents and increases their plasma levels, such as cytochrome P2C9 (CYP2C9) involved in the metabolism of sulphonylureas.16 That’s what oral hypoglycemic patients difficult to achieve glycemic control. Most recently, some investigators have suggested that for TB-DM patients, higher blood glucose levels contribute to the occurrence of drug resistance by delaying sputum conversion.17, 18 Glycosylated haemoglobin was very high in the patients who kept on OHA alone. Those patients kept on insulin and insulin with OHA was achieving glycemic control. The study showed improvement in insulin alone and along with OHA’s with DOTS showed improvement in glycogen control and lowered HbA1C levels as compared to OHA group patients.
Conclusion
The association between DM and TB is well documented and there is substantial evidence to support this fact. There is adverse interaction between anti-TB drugs and oral hypoglycemic agents. Particularly rifampcin is a potent inducer of hepatic enzyme cytocrome P450. cytocrome P450 rapidly metabolizes the oral hypoglycemic agents particularly sulfonylureas and brings the diabetic patients to uncontrolled glycemic status. Isoniazid decreases the metabolism of oral antiglycemic agents and increases their plasma levels, such as cytochrome P2C9 (CYP2C9) involved in the metabolism of sulphonylureas. Those patients kept on OHA alone there is more failure rates as compared with other two groups. TB patients kept on insulin and insulin with OHA showed better response and early sputum conversion, lowered blood glucose levels and HbA1C as compared with OHA people. Limitations of present study: small sample size.
