Association Between Diabetes Mellitus-Tuberculosis and the Generation of Drug Resistance

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the leading infectious causes of death globally, with drug resistance presenting a significant challenge to control efforts. The interplay between type 2 diabetes mellitus (T2DM) and TB introduces additional complexity, as T2DM triples the risk of active TB and exacerbates drug resistance development. This review explores how T2DM-induced metabolic and immune dysregulation fosters the survival of Mtb, promoting persistence and the emergence of multidrug-resistant strains. Mechanisms such as efflux pump activation and the subtherapeutic levels of isoniazid and rifampicin in T2DM patients are highlighted as key contributors to resistance. We discuss the dual syndemics of T2DM-TB, emphasizing the role of glycemic control and innovative therapeutic strategies, including efflux pump inhibitors and host-directed therapies like metformin. This review underscores the need for integrated diagnostic, treatment, and management approaches to address the global impact of T2DM-TB comorbidity and drug resistance.

Keywords: Mycobacterium tuberculosis; T2DM–TB binomial; drug resistance; efflux pumps; innate immune response; metformin; tuberculosis; type 2 diabetes mellitus.

Figure 1

The image presents three cases: one of a person with T2DM, another with TB, and a third with both T2DM–TB simultaneously. This figure illustrates how the immune response is altered in each condition, showing changes in the concentration of immune response cells and cytokines. These changes are represented with blue arrows for increases and red arrows for decreases. Additionally, it highlights that the presence of the T2DM–TB comorbidity promotes the development of DR, which worsens the clinical condition of patients.