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EFFECT OF DYSGLYCEMIA ON URINARY LIPID MEDIATOR PROFILES IN PERSONS WITH PULMONARY TUBERCULOSIS
Eicosanóides urinários
Mediadores lipídicos
Tratamento antituberculose
Mycobacterium tuberculosis
Urinary eicosanoids
Lipid mediators
Antituberculosis treatment
Author
Arriaga, María B.
Karim, Farina
Queiroz, Artur T. L.
Pereira, Mariana Araújo
Duarte, Beatriz Barreto
Sales, Caio
Moosa, Mahomed-Yunus S.
Mazibuko, Matilda
Milne, Ginger L.
Maruri, Fernanda
Serezani, Carlos Henrique
Koethe, John R.
Figueiredo, Marina C.
Kritski, Afrânio L.
Santos, Marcelo Cordeiro
Rolla, Valeria C.
Sterling, Timothy R.
Leslie, Alasdair
Andrade, Bruno B.
Karim, Farina
Queiroz, Artur T. L.
Pereira, Mariana Araújo
Duarte, Beatriz Barreto
Sales, Caio
Moosa, Mahomed-Yunus S.
Mazibuko, Matilda
Milne, Ginger L.
Maruri, Fernanda
Serezani, Carlos Henrique
Koethe, John R.
Figueiredo, Marina C.
Kritski, Afrânio L.
Santos, Marcelo Cordeiro
Rolla, Valeria C.
Sterling, Timothy R.
Leslie, Alasdair
Andrade, Bruno B.
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, Perú.
University of KwaZulu-Natal. Nelson R. Mandela School of Medicine. Department of Infectious Diseases. Durban, South Africa.
Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Salvador. Salvador, BA, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Salvador. Salvador, BA, Brasil.
Africa Health Research Institute. Durban, South Africa.
University of KwaZulu-Natal. Nelson R. Mandela School of Medicine. Department of Infectious Diseases. Durban, South Africa.
Vanderbilt University School of Medicine. Department of Medicine. Division of Clinical Pharmacology. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Faculdade de Medicina. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-Graduação em Medicina Tropical. Manaus, AM, Brasil / Universidade Federal do Amazonas. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Africa Health Research Institute. Durban, South Africa / University College London. Division of Infection and Immunity. London, United Kingdom.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Universidade Salvador. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
University of KwaZulu-Natal. Nelson R. Mandela School of Medicine. Department of Infectious Diseases. Durban, South Africa.
Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Salvador. Salvador, BA, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Salvador. Salvador, BA, Brasil.
Africa Health Research Institute. Durban, South Africa.
University of KwaZulu-Natal. Nelson R. Mandela School of Medicine. Department of Infectious Diseases. Durban, South Africa.
Vanderbilt University School of Medicine. Department of Medicine. Division of Clinical Pharmacology. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Faculdade de Medicina. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-Graduação em Medicina Tropical. Manaus, AM, Brasil / Universidade Federal do Amazonas. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.
Africa Health Research Institute. Durban, South Africa / University College London. Division of Infection and Immunity. London, United Kingdom.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Universidade Salvador. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Abstract
Background: 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 M. tuberculosis (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. Methods: We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had subgroups with or without dysglycemia at baseline. Participants were enrolled from RePORTBrazil (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) TBnormoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE₁ (metabolite of PGE2, TN-E), 9α-hydroxy11,15-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-PGF₁α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE₄). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy. Results: PGE-M and LTE₄ 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 LTE₄ 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 LTE₄ at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status. Conclusion: The urinary eicosanoid metabolite profile was associated with TBdysglycemia 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.
Keywords in Portuguese
DisglicemiaEicosanóides urinários
Mediadores lipídicos
Tratamento antituberculose
Keywords
DysglycemiaMycobacterium tuberculosis
Urinary eicosanoids
Lipid mediators
Antituberculosis treatment
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