Diabetes and tuberculosis: an emerging syndemic

Abstract

The intersection between diabetes mellitus (DM) and tuberculosis (TB) constitutes a significant and challenging public health concern. Tuberculosis, etiologically linked to the intracellular bacterium Mycobacterium tuberculosis (MT), remains one of the primary causes of infectious disease mortality globally. Within the epidemiological context of Argentina, diabetes mellitus represents the second most prevalent comorbidity associated with tuberculosis, surpassed only by the Human Immunodeficiency Virus (HIV). Importantly, diabetes mellitus triples the risk of developing active tuberculosis, whereas the active bacterial infection concurrently impairs glycemic regulation. This close bidirectional interaction establishes a pathological synergy (syndemic) that impedes early diagnosis, complicates therapeutic management, and critically compromises clinical outcomes.

Hyperglycemia induces severe alterations in both innate and adaptive immunity against MT. Key immunological impairments include reduced efficacy in bacterial recognition and phagocytosis, impaired recruitment of antigen-presenting cells, and delayed activation of the cellular immune response. Consequently, comorbid patients exhibit more extensive pulmonary disease, bilateral involvement, and a higher frequency of cavitary lesions.

Atypical clinical presentations—characterized specifically by lower lobe lesions—are observed in 10% of patients with DM compared to only 3% in the general population. These atypical radiographic findings are significantly more frequent in individuals with poorly controlled glycemic levels.

From a diagnostic perspective, individuals co-affected by TB and DM frequently present with positive sputum smear microscopies showing higher bacillary loads. Consequently, the TB-DM comorbid cohort is designated as a priority group for the utilization of rapid molecular assays, mycobacterial cultures, and drug-sensitivity testing. These patients face an elevated risk of clinical relapse, drug resistance, and mortality.

With respect to therapeutic management, patients with diabetes mellitus experience suboptimal treatment responses. This is partly driven by pharmacokinetic interactions, as rifampicin exhibits clinically significant drug-drug interactions with non-insulin pharmacological agents, such as sulfonylureas and metformin. Furthermore, clinical monitoring must be exceptionally rigorous due to a higher incidence and severity of adverse drug reactions associated with anti-tuberculosis therapy (ADRs) in this population. Specifically, comorbid patients face a fourfold increase in the risk of experiencing adverse therapeutic events, including peripheral and ocular neuropathies, steatosis-induced hepatotoxicity, and renal impairment.

Consequently, it is of paramount importance to consolidate an integrated, interdisciplinary approach that systematically implements the following clinical protocols: systematic screening for diabetes mellitus in all patients diagnosed with active tuberculosis. Active screening for tuberculosis in diabetic individuals presenting with persistent respiratory symptoms or refractory, unexplained metabolic dysregulation.