Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis.

[{"label":"BACKGROUND","text":"Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses."},{"label":"METHODS","text":"We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had sub-groups with or without dysglycemia at baseline. Participants were enrolled from RePORT-Brazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TB-normoglycemia (n=64); c) non-TB\/dysglycemia (n=31); d) non-TB\/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11\u03b1-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE (metabolite of PGE2, TN-E), 9\u03b1-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF\u03b1 (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy."},{"label":"RESULTS","text":"PGE-M and LTE values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p<0.001). In addition, there was a significant decrease in PGI-M and LTE levels from baseline to month 6 in the TB-dysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status."},{"label":"CONCLUSION","text":"The urinary eicosanoid metabolite profile was associated with TB-dysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia."},{"copyright":"Copyright \u00a9 2022 Arriaga, Karim, Queiroz, Ara\u00fajo-Pereira, Barreto-Duarte, Sales, Moosa, Mazibuko, Milne, Maruri, Serezani, Koethe, Figueiredo, Kritski, Cordeiro-Santos, Rolla, Sterling, Leslie, Andrade and the RePORT Brazil and South Africa consortia."}]