Frequency of tuberculosis among diabetic patients in the People’s Republic of China

Wang, Hong-Tian; Zhang, Jing; Ji, Ling-Chao; You, Shao-Hua; Bai, Yin; Dai, Wei; Wang, Zhong-Yuan

A previous study has demonstrated that DM not only increases the risk of TB but also adversely affects anti-TB treatment. 9 DM greatly diminishes the immune function of the human body, causing decreased protein synthesis and increased protein consumption, leading to a decreased ability to produce immunoglobulin and hindering lymphocyte transformation for immune protection. The populations of T cells, B cells, and antibodies are reduced and their functions are impaired. 10 Simultaneously, hyperglycemia can decrease the mobility, adhesion, and bactericidal phagocytosis of white blood cells. TB is more likely to occur in young, thin, and frail patients with DM, lipidemia, or vitamin A deficiency. Increased blood fatty acids provide good nutrition for tubercle bacillus proliferation. Vitamin A deficiency also facilitates Mycobacterium tuberculosis infection, as the bacterium is resistant to immune cells. 11 Vitamin A also influences the immune system and affects autoimmunity. One study found that blood retinol levels in type 1 diabetic rats were lower than in controls, indicating a close relationship between type 1 DM and vitamin A deficiency. 12 The DRB1*09 allele is susceptive to PTB complicated with type 2 DM, while the DQB1*05 allele may be protective to PTB complicated with type 2 DM. The DRB1*09 and DQB1*05 alleles may affect the incidence of PTB complicated with type 2 DM, or other real effect genes may link with them. 13 Gonzalez-Curiel et al 14 found that antimicrobialpeptide gene expression increases during progressive TB, which could be used as a biomarker for reactivation. In contrast, patients with type 2 DM have a lower gene expression of antimicrobial peptides, suggesting that these patients have an enhanced risk for TB reactivation. Two genes, HK2 and CD28, have been considered potential culprits in DM-increased TB susceptibility. 15 Compared with pre-DM status, the expression of both genes in DM decreased in each individual without exception. The HK2 gene encodes hexokinase 2, which is a critical mediator of aerobic glycolysis, the unique energy source for macrophages. HK2 has been implicated in the development of insulin resistance and DM in experimental studies. 15 Decreased expression of HK2 may impair macrophage function, thus increasing the risk of TB. The CD28 gene encodes T-cell antigen cluster of differentiation 28. The T-helper (Th)1 response plays a key role in activating macrophages in immunity against TB. After phagocytizing Mtb, proinflammatory macrophages present mycobacterial antigens to the T-cell receptors on the surfaces of cluster of differentiation (CD)4+ T lymphocytes. With costimulation by interleukin (IL)-12, mycobacterial antigens activate naïve CD4+ T cells and induce the generation of Th1 cells. In this process, the activation of T lymphocytes by the T-cell receptor complex after antigen recognition requires co-stimulation by CD28. Decreased CD28 expression in DM may impair CD4+T-cell activation and the Th1 response, thus increasing susceptibility to TB. 16, 17