|LETTER TO THE EDITOR
|Year : 2016 | Volume
| Issue : 3 | Page : 160-162
Tuberculosis and diabetes mellitus: A dual burden
Department of Pulmonary, Critical Care and Sleep Medicine, VMMC and Safdarjung Hospital, New Delhi, India
|Date of Web Publication||7-Oct-2016|
Dr. Pranav Ish
B-1, 1st Floor, Green Park Extension, New Delhi - 110 016
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Ish P. Tuberculosis and diabetes mellitus: A dual burden. MAMC J Med Sci 2016;2:160-2
It has been known for a long time that tuberculosis (TB) and diabetes mellitus (DM) have complex interactions, the mechanisms of which are not completely known yet. TB may have a different presentation in diabetics, and similarly, diabetic status is affected by TB and its treatment. It is important to understand these interactions as neither of them are an uncommon disease.  In fact, the interest in this dimension is increasing as it becomes more and more clinically relevant, with rampant TB and ever-growing DM population in our country.
Even though HIV infection is a strong risk factor for TB, it has been postulated that TB in DM is a big burden and needs to be addressed.  To be able to tackle this bidirectional association, we must understand the mechanisms and pathophysiology. In this article, the available literature will be reviewed, and the few official guidelines and recommendations available shall be discussed.
The burden of TB is ever rising. Increased life span and various socioeconomic factors have led to rise in prevalence in DM, especially specially type 2. The largest contribution has been from developing countries like India. With increasing prevalence of multidrug resistance TB (MDR-TB), the relationship is re-emerging as a public health problem. ,,
As far as latent infection is concerned, some studies did prove that diabetics are at a greater risk of acquiring TB; ,, however, there is ample evidence that the prevalence of TB is not increased in DM, if all other confounding variables are matched. , Diabetes was detected in 5.6% patients with active TB in a study performed in India. Nearly half of them had their diabetes diagnosed for the first time when their TB was detected.  There are multiple pathophysiological mechanisms postulated for this - decreased cell-mediated immunity, decreased cytokine response, low levels of gamma-interferon, micronutrient deficiency, and pulmonary microangiopathy. ,
Young patients with type 1 diabetes on insulin have a higher susceptibility to TB. Duration of disease, dose of insulin, ethnicity, and control of DM have been documented to be important risk factors. ,,
It has also been suggested that increased active TB is because of increased exposure and contact to patients due to frequent hospital and health-care center visits.  Both primary and reactivation of TB are common and frequent in DM, both type 1 and 2.  In summary, DM is a risk factor for active TB in all large-scale studies, independent of the prevalence of TB and type of study. 
There was conflicting evidence on the effect of DM on symptoms and clinical characteristics. However, it is prudent to say that extrapulmonary TB is less common and cavitary forms of TB are more common in DM, especially those on insulin and uncontrolled glycated hemoglobin (HbA1c) levels.  The common belief that lower lobe lung involvement is more common than upper lobe is unproven though lower lobe TB is more evident in DM when compared to nondiabetics. 
Delayed sputum conversion, underlying nephropathy, obesity with lower plasma levels of anti-TB drugs, and increased weight gain during treatment leading to therapy failure have been shown to be associated with worse outcome. , In conclusion, studies examining the effect of DM on TB are difficult to compare, and few of them have used bacteriological endpoints. There is no evidence to recommend alternative anti-TB regimen for diabetics. Consequently, treatment of TB is similar between diabetics and nondiabetics. 
Glucose intolerance and transient hyperglycemia have been reported in previously controlled diabetics. Inflammation caused by interleukin-6, tumor necrosis factor-alpha, hyperglycemic effects of isoniazid, rifampicin, and pyrazinamide, and drug interactions have been believed to be involved though a definite causation is yet to be established. ,,,,
It has been shown that screening for DM in TB can improve case detection, early treatment of both and prevent spread of infection. This is particularly relevant for India because the yield of screening increases with the prevalence of TB, and TB is widely rampant here. However, there are currently no special guidelines for screening for TB in this special population. It is prudent to screen any diabetic having cough for more than 2 weeks, weight loss, fever, or an abnormal imaging study for the presence of active TB. There is currently insufficient evidence for more active screening measure. , The American Thoracic Society has recommended performing tuberculin skin test with purified protein derivative for all diabetic patients. If the induration is 10 mm or more, prophylactic treatment with isoniazid is recommended for 6-12 months, unless the patient has had a history of TB.  Many other authorities have questioned the actual benefit and refuted this old recommendation. 
Screening for DM is recommended in all tubercular patients, even in India under Revised National Tuberculosis Control Programme where a random blood sugar is measured in all TB clinics before starting directly observed treatment short course chemotherapy.
According to the WHO, the preferred method for screening has not been determined. Fasting blood glucose, random blood glucose, 2 h postprandial glucose (2hPG), urine glucose, HbA1c, and performance of glucose tolerance test have been suggested. In Asian populations, the sensitivity of 2hPG is reportedly higher than fetal bovine serum and HbA1c. The WHO also recommends HbA1c as a diagnostic test for DM. However, it is expensive, and use of this test is still difficult on a large scale. 
The best time for screening is not yet clear. Some recommend screening later in the disease process, as an infectious disease, TB may transiently elevate blood glucose and an infection-related hyperglycemia may result in misclassification as DM.  On the other hand, early screening for DM has some benefits including initiation of treatment, patients' education, and correction of hyperglycemia, which could have positive effects on the outcome of TB treatment.
In addition, national TB programs in many countries refer TB patients to peripheral facilities where laboratory investigations are difficult to perform. Therefore, screening for diabetes is recommended at the start of TB treatment.  As hyperglycemia may regress after treatment of TB, verification of DM after cure of TB is necessary. Subsequent monitoring is also necessary because history of impaired fasting glucose is a strong predictor of subsequent diabetes. Due to these reasons, some recommend screening both at the time of diagnosis of TB and 3 months later after initiating treatment.  In India, screening is performed at the time of diagnosis of TB and start of treatment.
Recent studies in Southern India have shown that screening for TB in DM and vice versa are feasible and economical thereby helping in early detection of either and better treatment of both. It can be easily implemented using standard Revised National Tuberculosis Control Programme (RNTCP) and Adenosine Deaminase (ADA) guidelines. This is particularly useful in countries like India where prevalence of both is very high. 
Screening for TB among patients with DM is a good way to increase case finding for TB, which will lead to early detection, reduce transmission, and allow better management of TB. However, the advantage of bidirectional screening from the point of view of DM is not very clear. Patients with DM identified by this method are likely to be a fraction of the total load of DM. 
As mentioned before, it is imperative to understand and recognize this bidirectional relationship of TB and DM as screening and early treatment will prevent both mortality and morbidity. The interactions are complex and need to be studied in greater details on a large scale to deal with them in an efficient way. It may be the high time to start a joint program at the national level, perhaps similar to HIV-TB collaboration to control this mammoth joint epidemic. Well-designed large-scale studies are required to formulate guidelines on screening; whom and when to screen with what techniques, especially in view of newer tests such as cartridge-based nucleic acid amplification tests, and an era of emerging MDR-TB.
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Conflicts of interest
There are no conflicts of interest.
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