|Year : 2015 | Volume
| Issue : 1 | Page : 5-9
Glycemic control and radiographic manifestations of pulmonary tuberculosis in patients with type 2 diabetes mellitus
Sindhuri Avuthu, Vinay Mahishale, Bhagyashri Patil, Ajith Eti
Department of Pulmonary Medicine, KLE University's J. N. Medical College, Belgaum, Karnataka, India
|Date of Submission||07-Dec-2014|
|Date of Acceptance||12-Jan-2015|
|Date of Web Publication||17-Feb-2015|
Department of Pulmonary Medicine, KLE University's J. N. Medical College, Belgaum, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Diabetes mellitus (DM) is a risk factor for tuberculosis (TB) and may modify its presenting features. Atypical radiologic images of pulmonary TB are common in DM. Many studies have compared the radiological manifestations of TB between patients with and without DM. Aim of the Study: To study the impact of poor glycemic control on radiographic manifestations of the newly diagnosed smear-positive pulmonary TB patients with type 2 DM. Materials and Methods: In a tertiary care hospital, 70 patients newly diagnosed with smear-positive pulmonary TB and with coexisting type 2 DM were enrolled. Glycemic control was assessed by glycosylated hemoglobin (HbA1 C ). A pretreatment chest radiograph was read independently by two qualified pulmonologists blinded to patients' diabetic status. Films with any discordant reading were read by a third reader. Radiological lesions on chest radiograph were classified into minimal, moderately advanced and far advanced as per American Thoracic Society criteria. Results: Of 70 patients, 47 (67.1%) had their HbA1c level 7%. Patients with poor glycemic control (HbA1c 7%) were more likely to have lower lung field involvement (29.8% vs. 13.04%; P < 0.01), far advanced lesions (40% vs. 4%; P < 0.001) and cavitary disease on chest radiograph (76.6% vs. 43.4% P < 0.05). Conclusion: Poor glycemic control significantly influences radiographic manifestations of pulmonary TB in patients with DM. Uncontrolled diabetics seem to have multiple and large cavities. Also isolated lower lung field involvement is more common in uncontrolled diabetics than in optimal control patients. High index of suspicion is, therefore, required in uncontrolled diabetics when radiological patterns are atypical.
Keywords: Glycosylated hemoglobin, poor glycemic control, pulmonary tuberculosis, radiological manifestations
|How to cite this article:|
Avuthu S, Mahishale V, Patil B, Eti A. Glycemic control and radiographic manifestations of pulmonary tuberculosis in patients with type 2 diabetes mellitus. Sub-Saharan Afr J Med 2015;2:5-9
|How to cite this URL:|
Avuthu S, Mahishale V, Patil B, Eti A. Glycemic control and radiographic manifestations of pulmonary tuberculosis in patients with type 2 diabetes mellitus. Sub-Saharan Afr J Med [serial online] 2015 [cited 2023 Mar 27];2:5-9. Available from: https://www.ssajm.org/text.asp?2015/2/1/5/151564
| Introduction|| |
Tuberculosis (TB) continues to be a global problem as it is estimated to infect one-third of the world's population. Each year, there are over eight million incident cases of TB and almost one million people die of TB. In 2011, there were 8.7 million new TB cases, of which 5.1 million (59%) occurred in the Asia region.  The global burden of diabetes mellitus (DM) is expected to rise from an estimated 180 million prevalent cases currently to a predicted 366 million by 2030 with the greatest increase projected in the developing world.  There is rising concern worldwide about the twin epidemics of these two chronic diseases, especially in low to middle-income countries such as India and China. The escalating epidemic of DM may have a significant impact on global TB control. 
Among the 8.7 million new incident cases of TB, 2.2 million are said to have occurred in India accounting for a fifth of the global disease burden. The global burden of DM is increasing, and recent estimates highlight the importance of this disease in India.  There were an estimated 20-30 million people in India with diabetes in 2000 and projections suggest prevalence will rise to almost 80 million people by 2030. , It is possible that in areas of high DM prevalence the impact of this DM epidemic on TB could be as great as that of HIV. 
Radiographic manifestations of pulmonary TB in patients with DM have previously been studied extensively. Several studies reported that TB patients with DM had an increased frequency of lower lung field lesions as compared to TB patients without DM. A number of studies reported that TB patients with DM had a higher frequency of cavitations when compared with TB patients without DM. ,, Agrawal and Chang reported that the extent of disease was more advanced among TB patients with DM. 
However, all the studies conducted so far have compared the radiological manifestations of TB between patients with and without DM. It must be worth noting that radiographic manifestations of pulmonary TB are likely to be associated with immune status and the risk of developing TB among these patients with DM is likely to be dependent on glycemic control. While poor glycemic control is an important health event in DM patients with TB, there is very little information on whether poor glycemic control has any influence on the radiological manifestations of pulmonary TB. Thus, we undertook this study to determine the impact of poor glycemic control on radiological manifestations of the newly diagnosed smear-positive pulmonary TB patients with type 2 DM.
| Materials and methods|| |
Source of Data
In-patient and out-patient Departments of Pulmonary Medicine, Internal Medicine and Endocrinology sections at a tertiary care hospital, Belgaum, Karnataka, India.
This was a cross-sectional study of 70 newly diagnosed smear-positive pulmonary tuberculosis (PTB) patients who were also known/recently diagnosed to have DM. The study was conducted between January 2013 and December 2013. Inclusion criteria: 1. Age >/= 15 years. 2. Smear positive pulmonary TB according to the 2013 RNTCP (expand) criteria and DM.
(1) Both male and female patients newly diagnosed with smear positive pulmonary TB as per RNTCP criteria-2013 with type 2 DM (2) age >15 years.
Patients were excluded from the study if they have any of the following conditions:
- HIV infection,
- Connective tissue disorders,
- Chronic renal failure,
- Chronic liver disease,
- Malignancies on long-term steroid or cytotoxic drug therapy,
- Chronic alcoholics
- Previously treated for TB.
Patients and Methods
A total of 215 patients diagnosed as new smear-positive pulmonary TB attending inpatient and outpatient departments of Pulmonary medicine, Internal Medicine and Endocrinology sections at a tertiary care hospital were enrolled for the study after meeting the inclusion criteria as per RNTCP guidelines of India. A new smear-positive case is defined as a patient with one or more initial sputum smear examinations positive for acid-fast bacilli.  Informed consent was obtained from all study participants for the required investigations and purpose of the study. Baseline data were recorded, which included level of education, age, sex, years of smoking, body mass index, respiratory symptoms and symptoms-related to DM. Furthermore, patient's TB status including current and previous treatment records were noted carefully in detail. The screening and diagnosis of DM followed national guidelines, which stipulated that a fasting blood glucose (FBG) is used with cut-off thresholds in line with those recommended by WHO. In brief, FBG >126 mg/dl indicates DM; FBG ≥110 mg/dl to <126 mg/dl indicates impaired fasting glucose; FBG <110 mg/dl is normal.  The patients already known to have DM were directly enrolled in the study as known DM cases with TB. Patients whose diabetes status was unclear underwent random blood sugar testing and if it was more than 200 mg/dl, the subjects were further evaluated with fasting and postprandial blood sugars (FBS and PPBS). If FBS was more than 126 mg/dl or PPBS more than 200 mg/dl, the subjects were confirmed as having DM after which they were classified as new DM cases with TB. All the participants underwent glycosylated hemoglobin (HbA1c) evaluation. Patients with HbA1c levels >7% were considered to have poor glycemic control. 
The patients with pulmonary TB and DM were then subjected to chest radiography (posterior-anterior view). A pretreatment chest radiograph was read independently by two qualified pulmonologists blinded to patients' diabetic and TB status. The films with discordant reading were read by a third reader. Reading of the chest radiographs focused on lung parenchymal opacity and cavitation. Radiological lesions on chest X-ray were classified into minimal, moderately advanced and far advanced as per American Thoracic Society (ATS) criteria. Lower lung field , TB was defined as "tuberculous disease, found below an imaginary line traced across the hila and including the parahilar regions on a standard posterior-anterior chest roentgenogram." , Radiographic features were compared between patients with poor glycemic control and optimal glycemic control patients.
The categorical data were expressed as rates, ratios and percentages. Continuous data were expressed as mean standard deviation. The categorical data were analyzed using Pearson's Chi-square test, and continuous data were analyzed using Student's t-test. P < 0.05 was considered as statistically significant.
| Results|| |
We screened 215 newly diagnosed smear-positive pulmonary TB patients for DM. Of these, 86 subjects had known or newly diagnosed DM. Sixteen of these 86 patients were excluded from the study as they did not meet the inclusion criteria (HIV-3, chronic steroid therapy-2, chronic renal, hepatic conditions-4, malignancy-2 and five patients were lost to follow-up). Hence, 70 subjects were included in the final analysis.
Diabetes Mellitus Status
Among the 70 patients enrolled in the study 47 patients (67.1%) had their HbA1 C level ≥7% (poor control) and 23 patients had HbA1 C level <7% (optimal control). Fifty four (77.1%) patients were known diabetics and 16 (22.9%) were diagnosed after screening [Table 1].
Cavitatory and Noncavitatory Lesions
When radiographs were assessed 36 patients with poor glycemic control had cavitatory lesions, whereas only 10 patients in optimal control group had similar lesions. Noncavitatory lesions were noted in 11 and 13 patients respectively (P - 0.006). It was also noted with statistical significance (P - 0.05) that patients with poor glycemic control had multiple cavities and many patients had cavities larger than 3 cm compared with optimal control subjects [Table 2] and [Table 3].
Distribution of Lesions and the Severity of Tuberculosis
Isolated upper lung field lesions were predominantly observed in optimal control subjects (18 vs. 6). Isolated lower lung field lesions were primarily noted in poor control patients (14 vs. 3). Multi lobar involvement was noted in 27 subject with poor control group compared to 2 subjects in optimal control patients. All these observations were statistically significant (P < 0.01) [Graph 1].
As per ATS criteria, radiological severity between both the groups was compared. There was statistically significant difference in both the groups with five patients having minimal, 23 patients having moderately advanced and 19 patients with far advanced TB in poor control group when compared to optimal control group where 13 had minimal, 9 had moderately advanced and one patient had far advanced TB (P < 0.01) [Graph 2].
| Discussion|| |
Several studies have reported an association between DM and radiographic manifestations of pulmonary TB. The majority of studies have compared radiological manifestations in DM and nonDM patients with TB. A total of 70 patients were enrolled in this study, in which 47 patients had poor glycemic control and 23 had optimal control. To our knowledge, this is the first kind of study in India, where radiological manifestations of poor and optimal glycemic control patients with the newly diagnosed smear-positive pulmonary TB were compared.
Our study confirmed the findings in the previous study by Chiang et al. where the proportions of patients with DM with any cavity, cavitatory lesions over upper lung field, cavitatory lesions over lower lung field, large cavity (>3 cm) and multiple cavities were all highest among patients with poor glycemic control.  Present study was also in agreement with another study by Park et al. which demonstrated that poor glycemic control is linked with high frequency of cavitatory lesions. Park also reported that diabetic patients with poor glycemic control had an increased frequency of the cavity but not diabetic patients with proper glycemic control. 
Another striking study by Perez-Guzman et al. found that the TB-DM patients were older, and had a decreased frequency of upper (17% vs. 56%), and an increased frequency of lower (19% vs. 7%) and upper and lower (64% vs. 36%) lung field lesions. TB-DM patients developed cavitations (82% vs. 59%) more often in the lower lung fields (29% vs. 3%). Cavities were more often multiple in the TB-DM patients (25% vs. 2%). Statistical analysis with multiple logistic regression showed that being a diabetic patient was the most important factor determining lower lung field lesions and cavities. 
The present study however compared the poor glycemic and optimal control group which demonstrated that poor glycemic control subjects will have decreased the frequency of the upper lobe and increased frequency of lower lung field lesions compared with optimal control group. This observation is in line with the study by Chiang et al. suggesting glycemic control considerably influenced radiographic manifestations of pulmonary TB. The proportion of patients with lower lung field opacities was 67.5% in those without DM, 67.7% in those with DM with HbA1c <7%, 83.8% with HbA1c 7-9%, and 76.8% with HbA1c >9%. From multivariate logistic regression analysis adjusted for sex, age and smoking, the relative risk of lower lung field opacities was 0.80 (95% confidence interval [CI] - 0.46-1.42) for those with DM with HbA1c <7%, 2.32 (95% CI - 1.36-3.98) for HbA1c 7-9%, and 1.62 (95% CI - 1.12-2.36) for A1C >9%, compared with patients without DM.  The proportion of patients with extensive disease (moderately advanced and far advanced) in our study were more in the poor control group. This observation is in agreement with Perez-Guzman et al. and Chiang et al. As far as cavitatory lesions are concerned, Perez-Guzman reported that in patients with TB alone, cavitation became less common with age, whereas the frequency of cavitation remained high in diabetics of all ages which was noted also predominantly in poor glycemic control subjects in present study.
From the present study and many other studies discussed here, it is very important to note that poor glycemic control in TB and DM patients had great influence on radiological manifestations. Studies have shown that Indians are inherently more insulin resistant compared to other world population groups, notably Caucasians, and develop DM at a younger age. Westernization of diets, adoption of more sedentary lifestyles and urbanization are all suggested co factors in the epidemic of DM in India.  There were an estimated 20-30 million people in India with DM in 2000 and projections suggest prevalence will rise to almost 80 million people by 2030 with present national adult prevalence 0f 8.3%.  India with a population more than 1.27 billion has the highest number of both TB and DM patients. Escalating epidemic of DM is severely affecting TB control in India. In total 2/3 rd Indian population, reside in rural areas and smaller towns where facilities for diagnosis of DM are inadequate as HbA1c testing is not done routinely. There are inexorable evidence that uncontrolled and undiagnosed DM in TB patients have greater impact on the outcome of TB in the form of severity, quality of life, radiological manifestations, sputum conversion, hospital stay, health care costs, and death.
Tuberculosis also worsens glycemic control and makes the control of DM difficult. Maintenance of blood sugar level at normal or near normal level, is one of the most primary goal in patient care. , India-TB-Diabetes Study Group (corresponding author of the present article is also a member of the group) screened TB patients for DM and found prevalence of DM in tertiary care hospitals around 16% and in South India it was as high as 20% in patients with TB and they strongly recommended screening of all TB patients for DM at all levels of health care facilities.  This study further suggests that, screening for active DM in TB patients should lead to earlier detection of DM and optimal glycemic control will lead to a better outcome in TB treatment. Taken together, our findings propose that there should be a high degree of suspicion of TB in a patient with spectrum of typical radiological features having uncontrolled DM.
| Conclusion|| |
Poor glycemic control significantly influences radiographic manifestations of pulmonary TB in patients with DM. Uncontrolled diabetics seem to have multiple and large cavities. Also isolated lower lung field involvement is more common in uncontrolled diabetics than in optimal control patients. High index of suspicion is, therefore, required in uncontrolled diabetics when radiological patterns are atypical.
| References|| |
World Health Organization. Global Tuberculosis Report; 2012. WHO/HTM/TB/2012.6. Geneva, Switzerland: WHO; 2012. Available from: http://www.who.int/tb/publications/global_report/gtbr12_main.pdf. [Last accessed on 2014 Jun 30].
World Health Organization. Diabetes Fact Sheet No. 312; 2006. Available from: http://www.who.int/mediacentre/factsheets/fs312/en/index.html. [Last accessed on 2014 Mar 12].
Restrepo BI. Convergence of the tuberculosis and diabetes epidemics: Renewal of old acquaintances. Clin Infect Dis 2007;45:436-8.
Global Tuberculosis Report; 2012. Available from: http://www.apps.who.int/iris/bitstream/10665/75938/1/9789241564502_eng.pdf. [Last accessed on 2014 Jul 18].
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.
Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 2007;125:217-30.
Ponce-De-Leon A, Garcia-Garcia Md Mde L, Garcia-Sancho MC, Gomez-Perez FJ, Valdespino-Gomez JL, Olaiz-Fernandez G, et al.
Tuberculosis and diabetes in southern Mexico. Diabetes Care 2004;27:1584-90.
Pérez-Guzman C, Torres-Cruz A, Villarreal-Velarde H, Salazar-Lezama MA, Vargas MH. Atypical radiological images of pulmonary tuberculosis in 192 diabetic patients: A comparative study. Int J Tuberc Lung Dis 2001;5:455-61.
Aktogu S, Yorgancioglu A, Cirak K, Köse T, Dereli SM. Clinical spectrum of pulmonary and pleural tuberculosis: A report of 5,480 cases. Eur Respir J 1996;9:2031-5.
Shaikh MA, Singla R, Khan NB, Sharif NS, Saigh MO. Does diabetes alter the radiological presentation of pulmonary tuberculosis. Saudi Med J 2003;24:278-81.
Agrawal A, Nigam P, Agrawal M, Kumar R, Kapoor K, Gupta A, et al
. Overt diabetes mellitus in pulmonary tuberculosis. Lung India 1988;6:177.
World Health Organization; International Union Against Tuberculosis and Lung Disease; Royal Netherlands Tuberculosis Association. Revised international definitions in tuberculosis control. Int J Tuberc Lung Dis 2001;5:213-5.
Directorate General of Health Services, India. National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS). Available from: http://www.health.bih.nic.in/Docs/Guidelines-NPCDCS.pdf. [Last updated on 2014 Jul 10].
American Diabetes Association. Standards of medical care for patients with diabetes mellitus (Position Statement). Diabetes Care 2001;24:S33-43.
Chiang CY, Lee JJ, Chien ST, Enarson DA, Chang YC, Chen YT, et al.
Glycemic control and radiographic manifestations of tuberculosis in diabetic patients. PLoS One 2014;9:e93397.
Park SW, Shin JW, Kim JY, Park IW, Choi BW, Choi JC, et al.
The effect of diabetic control status on the clinical features of pulmonary tuberculosis. Eur J Clin Microbiol Infect Dis 2012;31:1305-10.
Zimmet PZ, McCarty DJ, de Courten MP. The global epidemiology of non-insulin-dependent diabetes mellitus and the metabolic syndrome. J Diabetes Complications 1997;11:60-8.
Jali MV, Mahishale VK, Hiremath MB. Bidirectional screening of tuberculosis patients for diabetes mellitus and diabetes patients for tuberculosis. Diabetes Metab J 2013;37:291-5.
Oluboyo PO, Erasmus RT. The significance of glucose intolerance in pulmonary tuberculosis. Tubercle 1990;71:135-8.
Basoglu OK, Bacakoglu F, Cok G, Sayiner A, Ates M. The oral glucose tolerance test in patients with respiratory infections. Monaldi Arch Chest Dis 1999;54:307-10.
India Tuberculosis-Diabetes Study Group. Screening of patients with tuberculosis for diabetes mellitus in India. Trop Med Int Health 2013;18:636-45.
[Table 1], [Table 2], [Table 3]
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