The rising prevalence of diabetes mellitus (DM) is undermining global efforts to eliminate tuberculosis (TB). Most studies found that patients with pulmonary TB and DM have more cavitary lung lesions, higher mycobacterial burden on the lungs, longer periods of infectiousness, and worse outcomes. Both human and animal studies indicate that TB-DM is associated with impaired innate and adaptive immune responses, resulting in delayed bacterial clearance. Similar observations have been noted in other infections, such as those caused by Klebsiella pneumoniae, where DM contributes to increased susceptibility and worse outcomes due to compromised immune functions including defective phagocytosis and impaired early immune cell recruitment. This review delves into the mechanisms of immune dysfunction in TB-DM, exploring how DM increases TB susceptibility and severity. By elucidating these complex interactions, this review aims to offer insights into more effective strategies for managing and improving outcomes for patients with this challenging comorbidity.

diabetes-tuberculosis

advanced glycation end products

Mycobacterium bovis bacille Calmette-Guerin

bone marrow derived macrophages

bronchoalveolar lavage

C-type lectin receptor

cytotoxic T lymphocytes

damage-associated molecular pattern

granulocyte colony-stimulating factor

high mobility group box 1

low- and middle-income countries

tumor necrosis factor alpha

Macrophage receptor with collagenous structure

monocyte-derived macrophages

Multi-drug resistant TB

major histocompatibility complex

Mycobacterium tuberculosis

matrix metalloproteinase

neutrophil extracellular traps

nicotinamide adenine dinucleotide phosphate

programmed death ligand 1

phorbol myristate acetate

reactive oxygen species

receptor for advanced glycation end products

latent tuberculosis infection

type 2 diabetes mellitus

Tuberculosis

Diabetes

Hyperinflammation

© 2025 The Author(s). Published by Elsevier Ltd.