Diabetes & tuberculosis: a dangerous liaison & no white tiger

Indian Journal of Medical Research, July, 2009 by Fiona Young, Julia Critchley, Nigel Unwin

Diabetes mellitus (DM) is becoming a global epidemic and India, in particular, is noted as hosting a high proportion of this disease burden. There are approximately 41 million prevalent cases of DM in India and as per the International Diabetes Federation (IDF) estimates by 2025 this will rise to about 70 million, the largest number for any country (1). As well as nationally predicted rises in DM rates, regional studies have also shown increasing rates of disease, with the largest reported increases in low and middle income countries occurring amongst urban populations(2). Surveys conducted in Chennai, India, in 1989 and subsequently in 1995 showed a 40 per cent rise in the prevalence of diabetes over this period (3). However, India not only faces the public health difficulties associated with newly increasing rates of chronic diseases such as DM, but as with other low and middle income countries, endures sustained rates of infectious diseases (such as TB) which remain to be brought under control.

One-fifth of the global TB incidence is from newly diagnosed cases within India; approximately 2 million people acquire TB yearly. Around 45 per cent of these incident cases will be individuals who have active TB, and are thus infectious to others, further increasing the high TB disease rates (4). It is estimated that annually around 331,000 people in India die from TB (5). The recent WHO report indicates that the prevalence of tuberculosis in India is 283 per 100,000 population with approximately 2.8 per cent of prevalent cases being problematic multi drug resistant (MDR) TB (5). It should however be noted that although TB rates are high in India, by 2006 directly observed treatment short-course (DOTS) was being provided nationally. In India, case detection is estimated to have increased from below 20 per cent up to 67 per cent as DOTS was set up throughout all 30 districts (4).

Rather than just existing alongside each other as diseases of high burden, TB and DM are thought to be associated with one another. Each disease is thought to be able to exacerbate the other and when an individual presents with both diseases concomitantly disease outcomes may be poorer. Reports on the association between DM and TB are found as far back as 1000 A.D. when Avicenna noted that 'phthisis', (a Greek term for tuberculosis), often complicated diabetes and that the presence of diabetes resulted in an increased risk of developing TB (6).

However, recently it has gone unmentioned in many global TB guidelines and in the most recent national guidelines has only been mentioned as something needing more research (5,7). If not acknowledged and dealt with appropriately, the association could pose a threat both to successful TB control and DM treatment.

Diabetes as a risk factor for TB

Patients with diabetes mellitus have been found to have a higher than average risk of contracting tuberculosis. A study carried out at the Regional Institute of Medical Sciences, Imphal, found the prevalence of pulmonary tuberculosis in people with diabetes to be 27 per cent by radiological diagnosis and 6 per cent by sputum positivity (8). In a study in Mumbai, tuberculosis was found to be the most commonly occurring concomitant illness in DM patients with 5.9 per cent of individuals in a cohort of over 8000 being co-morbidly affected (9).

A meta-analysis demonstrated that having diabetes was associated with an overall relative risk (RR) of 3.11 for contracting TB (10). A systematic review (11) reporting on the association found 9 studies in which diabetes was estimated to increase the risk of TB infection from 1.5 to 7.8 fold (11). Gender seems to have no bearing upon this relationship, however the RR for contracting TB amongst individuals with DM does vary by age, being highest in the younger groups (11).

In order to illustrate the potential public health importance of diabetes as a risk factor for TB, Stevenson et al (11) estimated the population attributable risk (PAR) for TB from DM within India. They calculated that diabetes could account for approximately 14.8 per cent of incident pulmonary tuberculosis (PTB) in India, and around 20 per cent of sputum positive cases (12). This calculation highlights the impact the diabetes epidemic could have upon TB rates in India, perhaps active case finding amongst people with diabetes will become appropriate in order to help control TB.

TB as a risk factor for diabetes

The majority of studies identify and discuss the presence of diabetes as a risk factor for TB but could the relationship between DM and TB be bi-directional? Engelbach (13) and Nichols (14) posited that not only could having diabetes increase an individual's likelihood of developing TB but that having TB could lead to the presentation of diabetes. Studies have also shown both a high prevalence of diabetes and of impaired glucose tolerance (IGT) in patients with tuberculosis (15). However, it is often not known if DM or IGT were present prior to TB infection as a high proportion of people with diabetes and especially IGT are unaware of their status.