Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil

Abstract

BackgroundDiabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil.MethodsOral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed.ResultsThe majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB.ConclusionsSustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted.

Severe pulmonary radiological manifestations are associated with a distinct biochemical profile in blood of tuberculosis patients with dysglycemia

“…Again, discrepancies driven by epidemiologic, clinical and even microbiologic factors may explain the conflicting findings. Despite the differences in clinical presentation, several studies reported similar results to those reported here, showing increased mycobacterial loads in sputum smears in hyperglycemic vs. normoglycemic patients [11,13,[26][27][28][29]. A multinational, harmonized, clinical study is necessary to formally demonstrate the effect of DM and/or PDM on TB disease presentation and to test if such effect is independent on the bacterial loads in sputum.…”

“…We have previously reported that patients with hyperglycemia more frequently present with multiple TBrelated symptoms compared to those with normoglycemia [11]. In addition, TB-DM patients more commonly required transfer from a primary care center to hospitals in order to have access to more complex care [11].…”

“…Both local and international agencies recommend both continuous screening for dysglycemia and tight glycemic control in people with active TB [9]. However, several factors limit the ability of individuals to properly monitor glycemic status/control [10,11].…”

“…The mechanisms underlying the clinical outcomes of patients with TB-DM comorbidity are poorly understood. Poor glycemic control seems to exacerbate the clinical presentation of TB [12][13][14], increasing the frequency symptoms [11] and the radiographic manifestations of pulmonary TB [15]. Other studies, however, have failed to demonstrate that DM impacts radiographic signs of TB [16].…”

Prediabetes is associated with the modulation of antigen-specific Th1/Tc1 and Th17/Tc17 responses in latent Mycobacterium tuberculosis infection

“…PDM has been shown recently to be associated with an increased risk of latent TB infection [7], to be associated with pulmonary TB in individuals with respiratory symptoms [8], and to be associated with dysregulated cytokine responses in pulmonary TB [9]. In addition, the prevalence of PDM has been reported to be as high as 25% in individuals with active TB [10].…”