Unique Reciprocal Association Seen Between Latent Tuberculosis Infection and Diabetes Is Due to Immunoendocrine Modulation (DM-LTB-1)

Abstract

AimThe prevalence of latent tuberculosis infection (LTBI) among diabetes patients is poorly studied. In the present study, the prevalence of LTBI among pre-diabetes and diabetes patients was studied, along with immunoendocrine biomarkers (n = 804).MethodsLTBI was screened by Quantiferon TB gold in Normal glucose tolerance [(NGT); n = 170, [Pre-diabetes (PDM; n = 209), Newly diagnosed diabetes (NDM; n = 165) and Known diabetes (KDM; n = 260) subjects. CRP, TNF-α, IL-6, IL-1β, IFN-β, IL-12, IFN-γ, IL-2, insulin, leptin, and adiponectin levels in serum and IFN-γ levels in quantiferon supernatants were quantified by ELISA. The expression of T-bet was quantified using qRT-PCR. Serum TBARS and nitrite levels were quantified by colorimetry.ResultsThe LTBI prevalence was 32% in NGT, 23% in PDM, 24% in NDM, and 32% in KDM groups, with an adjusted OR of 0.61 (p < 0.05). Downregulation of CRP, TNF-α, and nitrites and upregulation of adiponectin could be responsible for LTBI mediated protection against insulin resistance (IR), while the high levels of IL-1β, IL-12, and leptin could be responsible for IR mediated anti-TB immunity. The defective antigen-specific IFN-γ response, as seen in the KDM group, could be responsible for the low detection rate of LTBI and high probability of endogenous reactivation.ConclusionThere appears to be a biphasic relationship between diabetes-latent tuberculosis: At the early stages of diabetes it is reciprocal, while at a late stage it is synergistic, this important phenomenon obviously needs further research.

Immune-endocrine network in diabetes-tuberculosis nexus: does latent tuberculosis infection confer protection against meta-inflammation and insulin resistance?

“…Further, with respect to diabetes, most studies have been carried out only in chronic diabetes subjects, and what happens during the pre- and incipient of diabetes, is still an enigma ( 4 , 18 ). Recently, we carried out LTBI screening, among individuals with various grades of increasing glucose intolerance ( 19 ). We found a decreased prevalence of LTB among pre-diabetes (23%) and newly diagnosed diabetes patients (23%), compared to healthy controls (33%) and chronic diabetes patients (33%) ( 19 ).…”

“…Recently, we carried out LTBI screening, among individuals with various grades of increasing glucose intolerance ( 19 ). We found a decreased prevalence of LTB among pre-diabetes (23%) and newly diagnosed diabetes patients (23%), compared to healthy controls (33%) and chronic diabetes patients (33%) ( 19 ). It is important to note that gender plays an important role in disease susceptibility towards both diabetes as well as LTB.…”

“…It is important to note that gender plays an important role in disease susceptibility towards both diabetes as well as LTB. Male gender was a significant risk factor for both diabetes as well as LTBI ( 19 ). The exact reason for the decreased prevalence of LTBI among pre-diabetes subjects is not known.…”

“…It is characterized by a unique cytokine profile, which includes both innate and adaptive immune cytokines ( 21 , 22 ) ( Table 1 ). Increased circulating levels of innate immune markers including: Type-I interferon (Interferon-β), pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra and TGF-β) ( 19 , 23 , 24 ). TNF-α, IL-1β and IL-6 are known to activate macrophages and restrict mycobacterial growth ( 25 ).…”

Impact of diabetes mellitus on immunity to latent tuberculosis infection

“…These findings clearly reveal that due to metabolic dysfunction, an imbalance in the appearance of pro- and anti- inflammatory adipocytokines arises in TB-DM, which is an important feature that could influence the development of TB pathogenesis ( 63 ). There was a study by Aravindhan V et al., who have shown that inflammatory markers such as IL-1β, IFNγ and adiponectin were significantly elevated in LTBI individuals with newly diagnosed DM (NDM) in comparison to LTBI negative individuals with NDM ( 64 ). Subsequently from the same group, another study demonstrated that there was elevated IL-27 and IL-10 levels in the LTBI NDM, compared to LTBI group ( 65 ).…”