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Wawasan tentang Koinfeksi TB dan Diabetes

Pembicara: Dr.Arati Shahande

Consultant Physician & Diabetologist, Member- Diabetic Foot Society of India Governing Council, Pune

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Keterangan

Coinfection of tuberculosis (TB) and diabetes presents a complex healthcare challenge. TB-diabetes co-infection is increasingly prevalent due to the global rise in both diseases, particularly in countries with high TB incidence. Diabetes increases the risk of TB infection, and TB can worsen glycemic control in diabetics, creating a dangerous feedback loop. Co-infected individuals often face more severe TB symptoms, delayed treatment response, and a higher risk of TB drug resistance.Diabetes impairs the immune response, making individuals more susceptible to TB infection and complicating treatment.Accurate diagnosis can be difficult due to overlapping symptoms and the need for specialized tests to confirm both diseases. Managing both TB and diabetes simultaneously requires careful coordination of medications, as some anti-TB drugs may affect blood sugar levels.Routine screening for diabetes in TB patients and vice versa is crucial to identify coinfections early and provide appropriate care.Collaborative efforts between TB and diabetes healthcare teams are essential to ensure comprehensive care and better outcomes for co-infected individuals.

Ringkasan

  • Diabetes mellitus (DM) and tuberculosis (TB) are significant global health concerns, with DM ranked as the 9th leading cause of mortality in 2019 and TB ranked 13th. The combined impact of TB and HIV significantly elevates mortality rates beyond the sum of their individual contributions. India is expected to introduce its first adult TB vaccine, developed by the Serum Institute of India, within a year.
  • Global efforts are focused on ending TB by 2030, aiming for an 80% reduction in TB incidence and a 90% reduction in TB-related deaths. Key risk factors for TB include undernutrition, HIV/AIDS, smoking, alcohol use, and DM. DM significantly increases the risk of TB, with a prevalence overlapping significantly in low and middle-income countries.
  • TB and DM have a causal relationship. Systematic reviews reveal that DM increases the susceptibility to TB by approximately threefold, with this risk being higher in countries with high TB incidence. While race doesn't seem to be a direct factor, increased risk is associated with regions where TB and HIV prevalence are elevated.
  • In TB, approximately 30% of exposed individuals develop latent TB infection, where the immune system restricts but doesn't eliminate the bacteria. In DM, innate and adaptive immunity are impaired. The defects are more apparent during periods of extreme metabolic disturbance and are particularly evident in nosocomial infections. While vaccine efficacy generally remains intact, extreme hyperglycemia in T1DM can affect it.
  • DM-specific defects in innate and adaptive immunity, especially in the presence of extreme metabolic disturbances, impact the ability to clear TB infection. DM increases the likelihood of latent infection progressing to active TB. Lower T-lymphocyte response, impaired neutrophil function, and reduced antioxidant systems contribute to this increased susceptibility.
  • Microangiopathy and macroangiopathy, especially diabetic nephropathy, elevate the risk of TB. Precursor monocytes and alveolar macrophages in DM patients have reduced phagocytic activity, hindering their ability to kill bacilli. Chemotaxis is also affected, especially in the presence of high sugar levels, impairing phagocyte recruitment.
  • TB in DM patients leads to a higher susceptibility to active TB, a faster rate of conversion from latent to active infection, and a higher bacterial load. Clinical presentation can be atypical, leading to delays in diagnosis and an increased risk of drug-resistant TB, higher morbidity, mortality, and relapse.
  • TB can induce hyperglycemia through insulin resistance, persistent inflammation, and drug-drug interactions. A significant percentage of TB patients are diagnosed with new-onset diabetes. Metabolic changes associated with TB, such as dysregulation of lipid metabolism and elevated free fatty acids, can lead to insulin resistance.
  • MTV infection affects adipose tissue, leading to hypertrophy, immune cell infiltration, and altered adipokine production (less adiponectin, more leptin and resistin). This induces inflammation and releases more free fatty acids, further contributing to insulin resistance. Pro-inflammatory cytokines such as TNF-alpha and monocyte chemoattractant factor 1 (MCT1) are released, creating a vicious cycle.
  • MTV modulates the inflammatory process to favor its survival, leading to a non-resolving inflammation. TLRs (TLR2 and 4) are involved in signaling cascades for both hyperglycemia and immune response, further exacerbating the situation. MTV proteins induce glucose uptake in macrophages, leading to foamy macrophages, and disrupt host metabolic homeostasis.
  • Clinically, DM patients with TB can have pulmonary and extra-pulmonary TB. There is an increased risk of patient delay in diagnosis, and the disease is severe with multi-lobar involvement. Atypical radiographic patterns with lower lung involvement in older individuals cause further delay in diagnosis. Poor glycemic control is linked to cavity formation.
  • There are no evidence-based recommendations for DM and TB management. Optimal glycemic control should be achieved early, though achieving this is challenged by nausea, vomiting, reduced appetite, and unpredictable effects of TB treatment. Insulin is often the preferred choice due to fewer drug interactions. Metformin concentrations can be affected by rifampicin, potentially leading to hypoglycemia.
  • DM patients with TB often have low rifampicin levels, increasing the risk of MDR-TB. Therapeutic drug monitoring may be warranted. Factors affecting TB management in DM patients include active TB inflammation, behavioral problems, and healthcare system limitations. Long-term prognosis depends on diabetes management and TB drug sensitivity. Patient education and self-glucose monitoring are crucial.
  • WHO recommends collaborative activities for DM and TB, including coordinated surveillance, intensified TB detection, infection control, and high-quality TB treatment and DM management. Future research should focus on the effect of glycemic control on TB outcomes, screening techniques, prophylactic treatment, and healthcare delivery models in low and middle-income countries.

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