Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

Figure 1 Pathophysiological relationships between tuberculosis and diabetes mellitus and impacts of exogenous and endogenous factors. Both tuberculosis and diabetes mellitus show a bidirectional relationship at various points as depicted, which are affected by exogenous and endogenous factors. GH: Growth hormone; HCV: Hepatitis C virus; ART: Antiretroviral therapy; CTLA-4: Cytotoxic T-lymphocyte associated protein 4; PD-1: Programmed cell death protein 1; PDL-1: Programmed cell death ligand 1; IR: Insulin resistance; TB: Tuberculosis; COVID-19: Coronavirus disease 2019; HIV: Human immunodeficiency virus; MDR: Multi-drug resistant; XDR: Extreme drug resistance; TDR: Total drug-resistance; IL: Interleukin; TNFα: Tumor necrosis factor alpha.

Figure 2 Mechanistic insights into the pathophysiologies of tuberculosis and diabetes mellitus interactions. Mtb: Mycobacterium tuberculosis; IFN: Interferon; HDT: Host-directed therapy; Eis: Enhanced intracellular survival; ESAT-6: Early secretory antigenic target; ESX-1: Secretion system-1; vitD3: Vitamin D3; ROS: Reactive oxygen species; LAP: Microtubule-associated protein light-chain 3-associated phagocytosis; VDR: Vitamin D receptor; CAMP: Cathelicidin antimicrobial peptide; iNOS: Inducible nitric oxide synthase; RAAS: Renin–angiotensin–aldosterone system; IR: Insulin resistance; PXR: Rifampicin activates pregnane X receptor; N-CoR: The nuclear receptor corepressor; PPAR: Peroxisome proliferator-activated receptor; RXR: Retinoic acid receptor; ORF: Open reading frame; OATP2: The sinusoidal transporters organic anion transporting protein 2; DDIs: Drug-drug interactions; RIF: Rifampin.