Characteristics of PTB and non-TB patients.

<p>Patients with respiratory symptoms (n = 892) were screened for pulmonary tuberculosis (PTB) and classified as non-PTB or PTB according to culture positivity. Frequency data were compared using the Fisher’s exact test and continuous variables (age and BMI) were compared using the Mann-Whitney test. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#pone.0153590.t001" target="_blank">Table 1</a> for abbreviations.</p

Clinical, radiographic and microbiological profiles of patients with TB-diabetes comorbidity.

<p>(A) Prevalence of indicated TB-related symptoms were compared between patients with TB-diabetes (TBDM) comorbidity and non-diabetics (TB). (B) Frequency of lung lesions identified by chest radiography was compared between the study groups. Prevalence of AFB positive smear in TB patients with or without lung cavitary lesions (C) and in diabetic or non-diabetic patients (D) is shown. (E) AFB distribution profile in patients with or without cavitary lung lesion from either TB without DM or in TBDM patients. The Fisher’s exact test was used to assess statistical significance in in (A-D) whereas the chi-square test was used to compare data in (E).</p

Associations between cigarette smoking, glycemic control and pulmonary tuberculosis.

<p>(A) Frequency of smokers in the entire study population. (B) Frequency of TB diagnosis in smoking and non-smoking individuals with respiratory symptoms. (C) Prevalence of TB-related symptoms was compared between smoking and non-smoking PTB patients. (D) Frequency of AFB+ in sputum smears from smoking and non-smoking TB patients. In (B), (C) and (D), data were compared using the Fisher’s exact test. (E) Frequency of non-DM, pre-DM, DM (stratified according to HbA1c values) and those who referred previous diagnosis of DM in the groups of smoking or non-smoking individuals. Data were compared using the chi-square test. (F) Multinomial regression analysis adjusted for age, gender and BMI, was perform to test the association of the indicated conditions and pulmonary TB. The odds associated with the covariates used in the model adjustment are displayed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#pone.0153590.s001" target="_blank">S1 Table</a>.</p

Glucose metabolism disorder is associated with TB in patients with respiratory symptoms.

<p>(A) Stratification of patients presenting with respiratory symptoms based on HbA1c levels. (B) Frequency of abnormal HbA1c levels in patients diagnosed with pulmonary TB. (C) Frequency of TB cases in patients without previous DM diagnosis who were classified in non-DM, pre-DM and DM based on Hb1Ac. (D) Frequency of AFB+ in sputum smears from the entire study population. (E) Frequency of TB patients with different AFB smear grades in sputum classified according to altered HbA1c levels. (F) Prevalence of TB-related symptoms relative to the study population was compared between non-DM, pre-DM and DM TB patients without previous DM diagnosis. (G) Individuals were further categorized in polysymptomatic (> 3 symptoms) or non-polysymptomatic (≤ 3 symptoms). In (C), (D), (F) and (G), data were compared using the chi-square test.</p

Characteristics of population with previous diagnosis of diabetes according to the glycemic control status.

<p>Patients with respiratory symptoms who referred previous DM diagnosis (n = 80) were classified according to the glycemic control status based on HbA1c levels. Frequency data were compared using the Fisher’s exact test and continuous variables (age and BMI) were compared using the Mann-Whitney test. No patients in these groups referred illicit drugs use. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#pone.0153590.t001" target="_blank">Table 1</a> for abbreviations.</p

Characteristics of patients classified according to Hb1Ac levels.

<p>Patients with respiratory symptoms (n = 892) were screened for diabetes (DM) and classified as non-DM, pre-DM or DM following the American Diabetes Association criteria (non-DM: HbA1c < 5.7%, pre-DM: HbA1c 5.7–6.4%, DM: referred DM or HbA1c ≥ 6.5%). Frequency data were compared using the chi-square test and continuous variables (age and BMI) were compared using the Kruskal-Wallis test. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#pone.0153590.t001" target="_blank">Table 1</a> for abbreviations.</p

TB-diabetes comorbidity is associated with higher frequency of patient transfer to tertiary health care centers.

<p>(A) Frequencies of total undesirable events upon ATT initiation (death and transference to tertiary health care centers) in patients with TB or TBDM. (B) Frequencies of total undesirable events upon ATT initiation between patients with TB or TBDM with severe TB disease according to a composite score. (C) Frequency of death or transfer to tertiary health care centers in TB and TBDM patients. (D) Multinomial logistic regression analysis adjusted for age and gender was used to test association between TBDM comorbidity and the transfer to tertiary health care centers (OR, Odds ratio; 95%CI, 95% confidence interval). In (A) and (C), data were compared using the Fisher’s exact test. In (B), data were compared using the chi-square test.</p

TB-diabetes comorbidity is associated with increased TB severity assessed by a composite score.

<p>(A) The differences in median values (and IQR) between clinical score (left panel; only symptoms were considered) and composite score (right panel; symptoms, presence of cavitation and AFB+ in smear samples were considered) obtained in TB and TBDM groups were compared using the Mann-Whitney test. (B) Patients were further categorized in mild TB (<4points) or severe TB (≥4 points) using the clinical score (left panel). A similar stratification in mild TB (≤5 points) or severe TB (>5 points) was performed using the composite score. The frequency profile of TB and TBDM patients classified into severity categories was compared using the Fisher’s exact test. (C) Linear regression analysis were compared for clinical and composite score adjusted for age and gender was utilized to determine the association between increases of 1 point in the severity scores and presence of TB-diabetes comorbidity (OR, Odds ratio; 95%CI, 95% confidence interval).</p

Worse glycemic control is associated with pulmonary TB.

<p>(A) Left panel shows Hb1Ac levels in individuals who self reported previous diagnosis of diabetes. Full line represents median value (Hb1Ac = 8.45%). Dotted lines represent thresholds of Hb1Ac used to define normoglycemic levels (5.7%) and uncontrolled DM (7.0%) according to the ADA criteria [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#pone.0153590.ref018" target="_blank">18</a>]. Right panel shows frequency of individuals with respiratory symptoms who had referred previous diagnosis of diabetes and presented with poor glycemic control (HbA1c ≥ 7.0%). (B) Frequency of TB diagnosis (left panel) in patients referring previous DM diagnosis, with or without HbA1c ≥ 7.0%. Right panel shows frequency of TB cases with AFB+ sputum smears. The Fisher's exact test was used to assess statistical significance. (C) Linear regression analysis adjusted for age, gender and BMI was used to determine the association between increases of 1 unit in plasma values of HbA1c, fasting glucose or OGTT glycaemia (after log10 transformation) and pulmonary TB in the entire study population (n = 892). The odds associated with the covariates used in the model adjustment are displayed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#pone.0153590.s001" target="_blank">S1 Table</a>.</p

Characteristics of the Study Population.

<p>For more information in study design, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#sec006" target="_blank">Methods</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153590#pone.0153590.g001" target="_blank">Fig 1</a>. Frequency data were compared using the Fisher’s exact test and continuous variables (age and BMI) were compared using the Mann-Whitney test. BMI, body mass index; COPD, chronic obstructive pulmonary disease; IQR, interquartile range.</p