Project

The current epidemiology and future projections for tuberculosis (TB) and diabetes (DM) are frightening. In 2012, 9 million people will be diagnosed with TB, and 1.2 – 1.4 million will die from the disease. Globally, an estimated 366 million people live with diabetes mellitus (DM), a number expected to grow to at least 552 million by the year 2030, by which time over 80% of adult cases are expected to reside in low- or middle income countries.

Those with DM have three times the risk of developing active TB compared to the non-DM population and there are more TB patients with concomitant DM than are co-infected with HIV. It is estimated that DM now accounts for over 10% of TB cases worldwide, and this will increase significantly in the coming decades.

There is an urgent need for basic knowledge to help understand and control the linked epidemics of TB and DM. While the association between TB and DM is not mentioned in most international and national treatment guidelines and screening is not routinely carried out, awareness of the potential public health and clinical importance of the relationship between these two diseases is increasing. In 2011 the International Union Against TB and Lung Disease and the World Health Organization published a ‘Collaborative Framework for Care and Control of Tuberculosis and Diabetes’, to establish a co-ordinated response to the co-epidemic. From a clinical-operational point of view important data are lacking to improve care for patients with concomitant DM and TB.

From a pathophysiological point of view, data on the interaction of TB and DM are scarce. Therefore, there is an urgent need for involvement of basic sciences to help unravel the causal relationship between DM and TB, in order to design more effective strategies for control of both diseases.

The TANDEM consortium will address this vital issue. Our central hypotheses are that:

• Screening and management of DM among TB patients can be greatly improved and simplified with a major impact on control of TB-DM co-morbidity.
• The effect of DM on TB susceptibility and outcome is regulated, at least partly, by hyperglycemia, which dysregulates the cellular response to M. tuberculosis (Mtb), and by genetic variation common to both diseases.

To address these hypotheses we will use a comprehensive and integrated approach combining clinical, epidemiological and cutting edge expertise in laboratory sciences. We have brought together a multi-disciplinary consortium linking field sites in 4 TB-endemic countries that are experiencing a rapid growth of DM (Romania, Peru, South Africa, Indonesia), with leading laboratories in 4 European countries (Germany, United Kingdom, Netherlands, Romania).

We will address the following four objectives:

1. To identify feasible, accurate and cost-effective ways of screening TB patients for diabetes, and determine the prevalence of DM among TB patients and of TB in DM patients in different geographic areas.
2. To determine the level of DM management required during and after TB treatment, and the effect of glucose control on TB treatment outcome.
3. To identify key pathways which may account for enhanced susceptibility to, and poorer treatment outcomes of TB-DM by comparing gene expression and biomarker profiles in TB patients with, compared to those without, DM.
4. To establish the cellular and molecular basis responsible for the causal link between diabetes and TB, and in particular to determine the effect of hyperglycemia and genetic variation on the host protective response to Mtb.