IJTLD review examines animal models to further explore the dual burden of tuberculosis and diabetes

A recent review, published in the International Journal of Tuberculosis and Lung Disease (IJTLD) looks at the basic research that has been undertaken to model the tuberculosis-diabetes mellitus (TB-DM) interaction, using mice, rats and guinea pigs. The review, authored by researchers from the University of Massachusetts Medical School, aims to define the current state of knowledge, enabling the identification of gaps that may be addressed in future studies. The paper summarises findings from a number of animal studies that help to explain the clinical features of TB-DM comorbidity in humans.

The paper, Tuberculosis and diabetes: From Bench to Bedside and Back is published as part of the States of the Art series, available to subscribers to the ITJLD, including Union members.

The article lays out the current limitations of clinical research in TB in humans, including the inability to readily access samples from the major site of the disease in the lungs, and also the inability to study early events after M. tuberculosis infection. Regarding these limitations, one of the authors, Dr Hardy Kornfeld, says: “the animal model data implicate a delayed innate immune response to inhaled M. tuberculosis, which would be a major factor contributing to the later increased severity of TB disease.  By the time of diagnosis, this innate immune response is long back in the past, meaning that it could not have been discovered purely by clinical research approaches.”

While findings from research done using rodent models don’t always apply to humans, the authors of this review suggest that these models offer the best approach to overcome barriers that limit researchers’ ability to study early effects of disease. Despite the physiological differences between rodents and humans, the authors argue that animal models of TB-DM are sufficiently robust to explore fundamental disease mechanisms and novel therapies, while ensuring that subsequent clinical trials are optimised in terms of safety, efficacy, and cost-effectiveness.

Dr Hardy Kornfeld says “Understanding the mechanisms from the animal model data explain some of the clinical features of TB-diabetes comorbidity, and a combination of basic and clinical research can be applied to further validate the animal model data in people and to develop host-directed therapies that might be applied prior to TB infection.”

Diabetes increases a person’s likelihood of developing TB three-fold. Despite the recognised significance of DM as an acquired TB risk factor, the mechanisms behind this susceptibility are not fully understood. The authors suggest that further research should aim to increase understanding of the mechanisms driving TB susceptibility in people living with diabetes in order to influence the development of national TB programmes, as well as clinical and therapeutic interventions.

The authors of the paper are Dr Nuria Martinez and Dr Hardy Kornfeld from the Department of Medicine at the University of Massachusetts Medical School.

The International Journal of Tuberculosis and Lung Disease (IJTLD) is the official publication of The Union. It is distributed in over 165 countries world-wide. Further information about the journal and how to take out a subscription is available on The Union website.