The causes of type 1 diabetes are unknown, although the role of genetics is likely, since we can observe an association with some histocompatibility antigens, like HLA-DR3,-DR4 and DQ2; in particular, among genetic factors some haplotypes like HLA-DRB 09 seems to be linked to higher frequency of pulmonary tuberculosis associated with diabetes, while HLA-DQB has a “protective” role against the association. Besides, the higher frequency of both diseases in migrant populations stress the importance of the “environment” as a trigger. The link between these two diseases could be justified by immunological impairments that characterize diabetes, like lower CD4/CD8 ratio, impaired number and function of blood cells like granulocytes and monocytes. Literature shows that patients with both the diseases in response to protein purified derivative (PPD) have an overexpression of some inflammatory cytokines such as IL-2, IL-8, TNF-alpha and IFN-gamma (key Th1 cytokine, critical for tuberculosis control and usually up-regulated by M. tuberculosis). Among several hypothesis suggested to explain this paradoxical finding, the most plausible is focused on a modification in protein functions due to an increase in glycation products, which is responsible for a massive suppression of downstream signal transduction of Th1 lymphocytes and innate immunity cytokines, essential against Mycobacterium tuberculosis. One other possibility justifies the increased level in production of Th1 cytokines that is constantly observed in diabetic patients, with higher bacterial load in the lung in the early stage of tuberculosis, since, in fact, the increase in risk infection is a typical diabetic feature.
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