The dual disease burden of tuberculosis and diabetes (DM-TB) poses substantial challenges to diagnosis and treatment approach. Hyperglycemia is shown to be associated with severe tuberculosis, delayed culture conversion and poor prognosis. How diabetes impact pulmonary radiological manifestations of patients with tuberculosis is still unclear.
Previous studies demonstrated that hyperglycemia increased the risk of pulmonary TB incidence and was strongly associated with worsen pulmonary radiographic manifestation in TB patients[11]. TB patients with hyperglycemia presented with cavities and alveolar infiltrates more frequently than those with normoglycemia [12, 13]. Patients with uncontrolled diabetics with HbA1c > 9% were more likely to exhibit an increased number of cavity in lower lung field and more lobe involvement on chest CT[12]. HbA1c and FBG are often taken as indexes for glycemia control. Our findings indicated that multiple pulmonary cavities were often associated with changes in these two indexes. We also indicated that severe radiographic manifestations were associated with a systemic hyper-inflammation state characterized by elevation of WBC counts, neutrophil, monocyte, CRP and decreased lymphocyte in serum. Impaired innate immune responses had been described in many studies for patients with diabetes[14, 15]. Hyperglycemia combined with oxidative stress induce higher cytokines IL-17A, IL-8, and IL-10 in the lung which contributes to an exacerbated proinflammatory response[16, 17]. Some other components of innate immunity such as the function of neutrophils, macrophages, DC, NK cells are drastically compromised in individuals with DM which leads to delayed antigen presentation and impaired microbicidal activity [15, 18]. Persistent inflammation has been observed during anti-TB treatment in patients with diabetes [19]. We then inferred that over-expression of cytokines, such as CRP in TB-DM patients were associated with escalating neutrophil recruitment and infiltration, which led to more inflammation and necrosis, and then potentially resulted in cavity formation.
Another mechanism contributing to the severe inflammation is adaptive immune dysfunction. Impaired T helper 1 cell lowers production of IFNγ, which weaken the killing activity of macrophages and leads to failing control of mycobacterium growth[14]. High bacterial load and over inflammation in turn gives rise to development of more extensive lung lesions, cavitation and infiltration extending to more lobes[20]. Of note, our findings also indicated that decreased serum lymphocyte was linked to severe radiographic presentation of pulmonary TB, which also suggested that a compromised adaptive immune system might play an important role in the onset of active TB in patients with diabetes [21].
In addition, we noted from the findings that the level of HGB and ALB were lower in patients with multi-fragment infiltration. Individuals with malnutrition have been reported to be associated with severe pulmonary manifestation[22]. We believed that lower HGB and ALB in serum are indicative biomarkers of malnutrition and severe disease. It is also noteworthy that PCT level is seen to increase slightly in patients with more lung infiltration. PCT used to be taken as a robust biomarker for bacterial infection and sepsis[23]. It has been used to differentiate pulmonary tuberculosis from other pulmonary infections[24]. We thus speculated that bacterial co-infection should be noticed in patients with diffuse lung infiltration. Previous studies showed increased mycobacterial loads and higher proportions of smear positivity in hyperglycemic patients[3, 25, 26], our findings were in agreement and demonstrated that positive microbial results were frequently found in DM patients with pulmonary cavity and severe segment infiltration. The more severe the radiological manifestations, the heavier the bacterial burden.
There are some limitations in our study. Firstly, causal relationship between diabetes and severe radiological manifestation could not be set up according to our cross-sectional study design. Secondly, discrepancies driven by age, from symptom onset to diagnosis, clinical presentation and even other immune compromised factors were not stratified and further analyzed. Nevertheless, this internal analysis demonstrated an association between glycemic status, hyper-inflammation and the presentation of pulmonary lesions in TB-DM comorbidities.