Abstract
Diabetes mellitus (DM) increases tuberculosis (TB) susceptibility and worsens outcomes. Since inflammation and lipid metabolism are implicated in both diseases, we examined if combined TB and DM (TB-DM) increases inflammation or dyslipidaemia. In plasma from individuals with DM (n = 96), TB (n = 93), and TB-DM (n = 91), we measured 92 inflammatory proteins and 250 primarily lipid-related metabolites, repeating measurements after two months of TB treatment. Inflammation was primarily driven by TB, but higher in TB-DM. In TB-DM, the proteins osteoprotegerin (OPG), signaling lymphocytic activation molecule (SLAMF1), adenosine deaminase (ADA), interleukin-10 receptor subunit beta (IL-10RB), and tumor necrosis factor receptor superfamily member 9 (TNFSR9) were differentially abundant, and IL-17A/C predicted treatment failure. Disease severity correlated with inflammation and dyslipidaemia. Inflammation decreased with TB treatment, both in TB and TB-DM. Dyslipidaemia was primarily driven by DM, but more pro-atherogenic in TB-DM, with elevated VLDL and apolipoprotein B (ApoB). Despite TB treatment, pro-atherogenicity persisted. Stronger inflammation and dyslipidaemia may account for worse disease outcomes in TB-DM and warrant further action to prevent cardiovascular events.