Slow radiological improvement and persistent low-grade inflammation after chemotherapy in tuberculosis patients with type 2 diabetes

Abstract

Background: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease.Methods: Newly diagnosed pulmonary TB patients with or without DM (TB n=40; TB-DM n=40) were recruited in Dhaka, Bangladesh. Clinical symptoms, sputum smear and culture conversion as well as chest radiography were assessed. Peripheral blood and sputum samples were collected at the time of diagnosis (baseline) and after 1, 2 and 6 months of standard anti-TB treatment. Blood samples were also obtained from healthy controls (n=20). mRNA expression of inflammatory markers in blood and sputum samples were quantified using real-time PCR.Results: The majority of TB-DM patients had poor glycemic control (HbA1c>8%) and displayed elevated pulmonary pathology (P=0.039) particularly in the middle (P<0.004) and lower lung zones (P<0.02) throughout the treatment period. However, reduction of clinical symptoms and time to sputum smear and culture conversion did not differ between the groups. Transcripts levels of the pro-inflammatory cytokines IL-1β (P=0.003 at month-1 and P=0.045 at month-2) and TNF-α (P=0.005 at month-1) and the anti-inflammatory cytokine IL-10 (P=0.005 at month-2) were higher in peripheral blood after anti-TB treatment in TB-DM compared to TB patients. Conversely in sputum, TB-DM patients had reduced CD4 (P<0.009 at month-1) and IL-10 (P=0.005 at month-1 and P=0.006 at month-2) transcripts, whereas CD8 was elevated (P=0.016 at month-2). At 1- and 2-months post-treatment, sputum IL-10 transcripts were inversely correlated with fasting blood glucose and HbA1C levels in all patients. Conclusion: Insufficient up-regulation of IL-10 in the lung may fuel persistent local inflammation thereby promoting lung pathology in TB-DM patients with poorly controlled DM.