Tuberculosis and diabetes mellitus: a narrative review on the growing syndemic in low- and middle-income countries

Tuberculosis (TB) and diabetes mellitus (DM) represent major global health challenges, with their increasing coexistence forming a growing syndemic in low- and middle-income countries (LMICs). Type 2 diabetes (T2D) is reaching epidemic levels, exacerbating the burden of infectious diseases like TB—a leading global infectious disease—by increasing susceptibility and complicating management in resource-constrained settings. The interaction between TB and DM is bidirectional, with significant pathophysiological and clinical implications. This narrative review synthesizes current evidence on the epidemiology, pathophysiology, and clinical management of TB-DM co-infection in LMICs. It examines the bidirectional relationship where DM (hyperglycemia) impairs immunity (macrophages/neutrophils), while TB-induced inflammation (TNF-α, IL-6) leads to insulin resistance and worsened glycemic control, creating a feedback loop that complicates patient outcomes. The rising prevalence of DM, coupled with persistent TB epidemics in regions like South Asia and Sub-Saharan Africa, places substantial strain on overburdened healthcare systems in LMICs. Globally, India (27% of global TB cases, 75 million DM cases), China (10% of global TB cases, 98 million DM cases), and South Africa (TB incidence: 513 per 100,000, 11% DM prevalence) are among the top 3 high TB burden countries, collectively accounting for 87% of the world’s TB cases (WHO, 2023; IDF Diabetes Atlas, 2021). DM increases the risk of developing TB (relative risk [RR] 3.11, 95% CI 2.27–4.26, p<0.00001), with poorly controlled blood glucose further heightening susceptibility, while TB exacerbates glycemic control, necessitating complex clinical management. Diagnostic challenges, insufficient resources, workforce shortages, inadequate training, and a lack of integrated care models contribute to delays in diagnosis and treatment of co-infected patients. Addressing the TB-DM syndemic in LMICs requires a multifaceted approach, integrating expertise in infectious and chronic disease management. Task-shifting, digital health tools, and coordinated multidisciplinary care offer promising solutions to mitigate the dual burden. This review underscores the urgent need for tailored interventions and policies to improve patient care and public health outcomes in the context of TB-DM co-infection.