Background:
Diabetes mellitus (DM) significantly increases the risk of developing active pulmonary tuberculosis (TB) and experiencing adverse treatment outcomes, such as delayed sputum conversion, treatment failure, and death. While individuals with TB and concurrent DM (TBDM) are known to exhibit systemic hyper-inflammation at the time of diagnosis, the long-term impact of anti-TB treatment (ATT) on this inflammatory pattern remains poorly understood.
Abstract:
Methods: We measured 17 plasma cytokines and growth factors in longitudinal cohorts of pulmonary TB patients with and without DM from India ($n=87$) and Brazil ($n=51$). Assessments were conducted at diagnosis (baseline) and during the 6-month course of ATT; the India cohort was also evaluated one year after treatment completion (month 18).
Results: Principal component analysis showed a clear separation between TBDM and TB patients at baseline, with TBDM groups exhibiting higher levels of nearly all pro-inflammatory analytes in both countries. This systemic hyper-inflammation in TBDM persisted through the end of treatment at month 6. Although inflammation eventually resolved and converged by one year after treatment completion (month 18) in the India cohort, TBDM was initially hallmarked by significantly lower levels of the anti-inflammatory cytokine IL-10.
Conclusions: DM comorbidity is associated with a hyper-inflammatory phenotype that resolves more slowly than in normoglycemic TB patients. This persistent inflammation likely contributes to increased morbidity and risk for TB-related mortality, highlighting the potential benefit of anti-inflammatory host-directed therapies for TBDM patients.
Keywords: diabetes; prediabetes; treatment outcome; Mycobacterium tuberculosis; systemic inflammatio
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- Data de Publicação: 04/07/2019
- Autores: Nathella Pavan Kumar1†, Kiyoshi F Fukutani2,3,4†, Basavaradhya S Shruthi5 , Thabata Alves2,6, Paulo S Silveira-Mattos2,4, Michael S Rocha2 , Kim West7 , Mohan Natarajan8 , Vijay Viswanathan5 , Subash Babu1 , Bruno B Andrade2,3,4,6† , Hardy Kornfeld7
