THE RELATIONSHIP BETWEEN TYPE-2 DIABETES AND TUBERCULOSIS.

According to the experimental and clinical investigations, innate and adaptive immune disorders play a significant role in T2-D subjects to become more susceptible to TB. It was shown that the functions of neutrophils, macrophages, NK cells and other components of innate immunity areis markedly compromised by metabolic disorders in T2-D. The number of evidences suggests that reduction in TH1:TH2 cytokines ratios may have significant influence on susceptibility of TB infection in T2-D subjects. Hormonal changes in T2-D also may increase susceptibility to TB, including 2 hormones -ghrelin and leptin that are involved to in controlling blood glucose levels related to malnutrition during TB. According Based on the experimental and clinical results resistin, being a key molecule that links obesity and TB2-D, is considered as a protein contributing contributor to the development of insulin resistance, being a key molecule that links obesity and TB2-D. Subjects with T2-D showed higher levels of resistin in serum associated with reduced possibility of human macrophages to enhance the production of reactive oxygen species (ROS) in vitro against a challenge with TB. Immunological impairment has an important role in susceptibility to TB infection for patients with T2-D. It has been revealed that IFN-y and IL-22 markedly discriminate diabetes from nondiabetic individuals. It was also established that aside from this many cytokines such as IL-17A, IFN-B, TNFα, IL-10, IL-18, IFN-Y and IL-22 are the most significant and consequently potentially related to the effects caused by diabetes caused effects in the pathogenesis of active pulmonary TB. The endothelial system plays significant role in the pathogenesis and progression of TB infection. It was demonstrated that endothelin "B" receptor antagonist leads to vasoconstriction precluding inflammatory cell infiltration in lung tissue, suggesting that ET-1 proinflammatory action involves ET "B" receptor. It was also shown that sputum endothelin-1 level is associated with active pulmonary tuberculosis and effectiveness of treatment. Reduction ins sputum ET-1 level has significant role in the assessment of anti-tuberculosis treatment efficacy. Alterations in microbiota in T2-D subjects may influence on immunity against TB infection. As it was established the amount of bacteria producing short-chain fatty acids (SCFA) markedly decrease in T2-D, and treatment with SCFA reduced induction of TFN-α, IL-10 and IL-17 cytokines in contrast to IL-6, IFN-y and IL-22, without modification of their induction after using of SCFA. Vitamin "D" deficiency in T2-D may also play a role ion the immune response against TB. A number of evidences suggest the correlation between its diminished levels and TB or TB-T2-D. In conclusion it is suggested that different risk factors, including immunological and hormonal changes as well as alterations in different cytokine production and microbiota, endothelial dysfunction and vitamin "D" deficiency are the main contributors leading to comorbidity of T2-D and in TB.