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 Table of Contents  
Year : 2018  |  Volume : 9  |  Issue : 3  |  Page : 81-87

A comparative study of clinical variables in tuberculosis patients with coexisting diabetes

1 Department of Community Medicine, G. R. Medical College, Gwalior, Madhya Pradesh, India
2 Department of Ophthalmology, SMS Medical College, Jaipur, Rajasthan, India

Date of Web Publication22-Aug-2018

Correspondence Address:
Dr. Anil Kumar Agarwal
4, Medical College Campus, G. R. Medical College, Gwalior - 474 009, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jod.jod_7_18

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Background: Diabetes mellitus (DM) is recognised as an important risk factor for tuberculosis (TB). India has high-TB burden, along with rising DM prevalence. Aim: This study was conducted to document the co-existence of DM and TB in persons with established TB and difference in clinical presentation. Type of Study: This was a cross-sectional, descriptive observational study conducted at selected directly observed treatment (DOT) centre in Gwalior North-Central India. Materials and Methods: A total of 550 patients of confirmed diagnosis of TB and on treatment were recruited. The study participants were screened for DM and diagnoses were made on the basis of the World Health Organization criteria. Clinical parameters were compared between persons with DM and those without DM. Results: DM/TB comorbidity was noted in 85 persons, and these made up 15.4% of the study population. Mean age was higher in DM patients with TB (43.4 ± 15.4 vs. 33.1 ± 16.2 years, P = 0.000); the mean duration of symptoms of TB with DM was more (124 ± 16.4 vs. 107.49 ± 10.3 days). Majority of the patients (63.5% dysglycaemic and 43.6% normoglycaemic TB patients) were presented with a cough with or without expectoration and significantly found more in dysglycaemic TB patients (odds ratio = 2.2, P = 0.007). The frequency of reporting symptoms was higher among dysglycaemic TB patients as compared to normoglycaemic TB patients. This difference in both groups was found to be statistically significant (P < 0.05) for pleural effusion, fever, shortness of breath, chronic abdominal pain, fatigue/weakness and in other non-specific symptoms. Conclusions: Given the substantial burden of DM and TB co-morbidity, this study makes a contribution for re-echo the need to raise awareness on screening for DM in persons with TB.

Keywords: Clinical symptoms, comorbidity, diabetes mellitus II, tuberculosis

How to cite this article:
Agarwal AK, Agarwal N, Mahore R. A comparative study of clinical variables in tuberculosis patients with coexisting diabetes. J Diabetol 2018;9:81-7

How to cite this URL:
Agarwal AK, Agarwal N, Mahore R. A comparative study of clinical variables in tuberculosis patients with coexisting diabetes. J Diabetol [serial online] 2018 [cited 2022 Oct 6];9:81-7. Available from: https://www.journalofdiabetology.org/text.asp?2018/9/3/81/239566

  Introduction Top

In recent decades, with the increasing prevalence of tuberculosis (TB), particularly multi-drug-resistant TB, and diabetes mellitus (DM) cases in the world, the relationship of DM and TB is re-emerging as a significant public health problem. The link of DM and TB is more prominent in developing countries where TB is endemic, and the prevalence of DM is rising. According to the World Health Organization (WHO), 180 million people are suffering from diabetes worldwide, and it is likely to double in the next 19–20 years, i.e., by 2030.[1] The epidemic growth of DM has occurred in developing countries where TB is highly endemic. As a result, DM and TB are increasingly present together, and this calls for renewed interest in this topic.[2] India is facing the dual problem of being the highest TB-burden country having a large number of people with diabetes posing a serious challenge for the health system.[3],[4]

The relationship between DM and pulmonary TB has attracted the interest of many clinicians and investigators for a long time. Many studies have shown that the prevalence of TB among diabetics is 2–5 times higher than in the non-diabetic population.[5] On the other hand, there appears to be little information on whether DM affects the diagnostic findings in TB. Diabetes has long been known to be a risk factor for active TB and reactivation of latent TB. It is also associated with worse TB clinical outcomes. Presence of DM can cause increase in blood glucose levels, and persistent hyperglycaemic levels can have a negative impact on presentation and outcome of TB. The clinical manifestations of TB may differ from the findings in non-diabetic TB patients as was initially reported by Perez-Guzman,[6] who found a higher rate of lower lung field (LLF) involvement in their diabetic patients. This was followed by other studies which reported that DM modifies the clinical features of TB. In a recent study from Mexico, diabetic patients were older, had LLF lesions and had more multiple cavities.[6] In a Turkish study,[5] DM did not affect the presenting features of pulmonary TB and was only associated with LLF disease in females and in older patients. Another study from Saudi Arabia showed similar symptoms, radiographic distribution and cavitary disease in diabetic and non-diabetic patients with pulmonary TB.[7] Asian patients from the Indian subcontinent have a higher incidence of insulin resistance and associated complications.[8]

The fact that diabetes will worsen the burden of TB-like communicable diseases could be the straw that breaks the camel's back for some health systems, on the other hand, this interaction between TB and diabetes could provide the wake-up call that health providers need to kick National health control/prevention programmes into action.[9] Adding the increasing burden of diabetes and TB into the mix will be an extrastrain with which many countries will struggle to cope. Since the risk of developing TB is more likely in diabetic patients, this correlation between diabetes and TB could have a negative impact on any efforts being made to control TB.[10] There is little information on whether DM affects the presentation, radiographic manifestations and clinical course of pulmonary TB for Asian patients from the Indian subcontinent.[8] With the following rationale in mind, this study was conducted to estimate the prevalence of impaired glucose tolerance in diagnosed cases of TB and determine various study variables and clinical factors that may be associated with the same retrospectively. The aims of this study were to determine whether DM alters the clinical manifestations of TB patients and to compare the other parts involvement by TB with or without diabetes.

  Materials and Methods Top

This study took place at the outpatient clinic of the direct observed short-course treatment centres for TB at a revised national TB control unit facility in Gwalior District and the duration was for 6-months. The study was approved by the Research and Ethics committee of the G.R. Medical College Gwalior. Informed and written consent were obtained from the study patients. All those who registered for Directly Observed Treatment, Short Course (DOTs) in these TB units during July 2016–December 2016 and meeting the selection criteria age ≥18 years. Pulmonary TB (PTB) cases confirmed with sputum smear for acid-fast bacilli and X-ray, and extrapulmonary cases confirmed with the culture of the specimen from the site and or histological evidence were included. Diagnosis of TB was based on standard diagnostic criteria of the Revised National TB Control Program.[11] Patients with Type I diabetes were excluded from the study. After identification of sampling frame, cluster random sampling technique was used to recruit the study participants. The sample size was calculated using the formula n = Z2 pq/L2. Where z is the standard estimate and = 1.96, P is prevalence given as 0.5 in this study, q = 1−P and d is precision at 0.05. Prevalence of diabetes among TB patients (P) was taken 25% in the account based on related studies conducted earlier[12],[13],[14] with allowable error (L) was 15%. Hence, the sample size was 533 which was the minimum sample size and we had taken 550 consecutive patients for rounded off convenience.

Thus 550 consecutive patients with physician-diagnosed TB (both pulmonary and extrapulmonary) who consented were recruited into the study. Random blood glucose was done in all patients with a glucometer. DM was diagnosed if random blood glucose level was >200 mg/dl in accordance with the WHO guidelines.[15] Random plasma/blood sugar level values between 140 and 200 mg/dl were considered as pre-diabetes. Physical assessment that was done included measurement of weight (kg) and height in meters and also the body mass indices calculated. Patients suffering from TB with no history of diabetes and with normal blood glucose level on screening will be included in Normoglycaemic Tb patients. A pretested questionnaire was administered to collect information regarding sociodemographics and habitual risk factors, namely, smoking, alcohol consumption and other forms of tobacco use; family history of TB and DM, educational and occupational status, and monthly per capita income. Type of TB, the status of TB treatment, and category of treatment were also recorded. Recall data on known symptoms indicative of TB or diabetes were collected through interviews using a questionnaire; the patients were asked whether they, during the past month, had experienced fever, polyuria, polydipsia, skin ulcerations, visual impairment, weight loss, cough, haemoptysis or night sweat. We chose a broad-spectrum of para-clinical parameters as well as a qualitative morbidity interview to investigate the impact of diabetes on the clinical manifestations of TB. Socio-economic status of the study participants was classified according to Agarwal AK Classification based on the latest AICPI of India and per capita income.[16]

Statistical analysis

The study participants were classified into 'Dysglycaemic TB' and 'Normoglycaemic TB' group. Further analysis of different variables was performed for both groups separately. The analysis was performed using Epi info version 7 7 )Centers for Disease Control and Prevention (CDC), Atlanta, Georgia (US) and licensed as public domain) with Epical and Microsoft Excel software. All quantitative data were expressed as a mean ± standard deviation the comparison of means was done using the Student t-test while qualitative variables were compared using the Chi-square. Univariate odds ratio (OR) was calculated as an estimate for relative risk (OR) with 95% confidential interval. P < 0.05 was considered as statistically significant.

  Results Top

The recorded response rate was 95.15%. A total of 550 patients with established TB participated in the study. [Table 1] shows the comparison of the anthropometric and other study characteristics among patients with normoglycaemic and diabetes. The age range of the patients was between 18 and 80 years. The mean age of normoglycaemic TB patients was 33.1 ± 16.2 years while the mean age of dysglycaemic TB patients was 43.4 ± 15.4 years and this difference was statistically significant (P = 0.001). DM was documented in all age groups of patients with TB, but patients with DM and TB comorbidity were significantly older than patients with TB without DM. The mean duration of symptoms (in days) was 281 (± 58) in dysglycaemic TB patients while in normoglycaemic was 268 (± 46) days and this was found statistically significant (P = 0.022). Among 351 TB patients, DM was present in 20 (5.7%). As expected, random plasma/blood glucose levels were statistically significant between both groups (P = 0.001). Mean body mass index (BMI) of the dysglycaemic TB patients was less (18.0 ± 2.9) than the normoglycaemic, but it was not found significant statistically (P < 0.05). Waist circumference in both genders (male: 87.73 ± 6.74; female: 82.06 ± 5.8) and blood pressure (systolic as well as diastolic blood pressure) were found significantly higher in normoglycaemic TB patient when compared to dysglycaemic TB patients (P < 0.05).
Table 1: Comparison of anthropometric and other study characteristics in diabetic and non-diabetic tuberculosis patients

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Lungs were the most common site of TB infection in normoglycaemic and dysglycaemic TB patients (58.8% and 41.9%, respectively). The different sites of extrapulmonary involvement in glycaemic and normoglycaemic TB patients are presented in [Table 2]. Pleural effusion was found to be the most common extrapulmonary site of infection in TB patients with normoglycaemic (22.2%) and dysglycaemia (31.4%) with OR 1.6 but that difference was not statistically significant (P = 0.22). The odds of developing skin TB and others sites were the highest (OR = 5.4 and 3.6) among both groups dysglycaemic and normoglycaemic TB patients, respectively, and were also found statistically significant.
Table 2: Distribution of normoglycaemic and dysglycaemic tuberculosis patients according to site of extra pulmonary tuberculosis infection

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Clinical signs and symptoms in both groups are shown in [Table 3]. The most predominant symptom of TB was weight loss which was present in 363 (66%) of the patients and was significantly more in the patients with diabetes 77.6% in comparison to non-diabetic (63.9%) with OR = 1.9 and P = 0.013. Majority of the patients (63.5% dysglycaemic and 43.6% normoglycaemic TB patients) were presented with a cough with or without expectoration and significantly found more in dysglycaemic TB patients (OR = 2.2, P = 0.007). The frequency of reporting symptoms was higher among dysglycaemic TB patients as compared to normoglycaemic TB patients. This difference in both groups was found to be statistically significant (P < 0.05) for fever, shortness of breath, chronic abdominal pain, fatigue/weakness and in other non-specific symptoms, but in overall, the difference was found to be statistically insignificant.
Table 3: Comparison of clinical symptoms among tuberculosis patients with diabetes and Normoglycemia (n=550)

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  Discussion Top

The association between DM and TB is well documented, and there is substantial evidence to support the fact that diabetes is an important risk factor for prominent TB clinical symptoms.[17]

From the total number of TB patients who were studied, 15.5% had coexisting DM. The mean age of the patients with TB and DM was higher than in those with TB alone. This is similar to the study in the United States.[18] This may be related to the fact that Type 2 DM is seen more frequently in the older age group; the fact that this study was conducted largely among adults with TB may also be a factor. In our study, majority of the patients were presumed to have Type 2 DM with only 25% of the patients studied being 30 years and below.

Global TB control efforts could be adversely affected by a high prevalence of diabetes. Diabetics are not only more prone to contracting TB but their response to initial intensive phase 4-drug anti-TB treatment is slow as well. This was clearly observed in this cohort of dysglycaemic TB patients in our study who stayed longer 14 days in average for intensive phase treatment when compared with their fellow non-diabetic patients (281 [± 58] vs. 268 [± 46]) days. This is similar to the finding of Gupta et al.[19] in India where they found a significantly higher duration of treatment of TB in patient with DM. It is likely owing to altered or impaired immune system response in diabetic patients. None of the diabetic TB patients had multi-drug resistant TB.

With regard to the factors associated with diabetes among tubercular patients, the present study found that as in general population, increasing age, higher BMI values and systolic blood pressure were significantly associated whereas waist circumference did not show any significant correlation and these all similar with a study done by Viswanathan et al.[13] on the prevalence of risk factors in TB patients in Tamil Nadu observed that age, BMI, positive family history of DM and sedentary occupation were the common risk factors associated with diabetes among TB patients and by Raghuraman et al.[20] found that age, family history and current alcohol consumption were found to be independent risk factors for diabetes in TB patients in the binary logistic regression analysis. BMI, waist circumference, the category of treatment and sputum positivity had no significant association. However, the mean random blood sugar of diabetics was higher than that of non-diabetics (185.3 ± 62.4 mg/dl vs. 108.4 ± 17.0 mg/dl; P = 0.001).

This study has not found any significant association between BMI or waist circumference and diabetes. Similar results were reported by studies by Jain et al.,[21] Raghuraman et al.[20] A study has reported that patients with TB and DM are significantly underweight and have more weight loss[22] while Alisjahbana et al.[23] have reported a significantly higher median BMI in TB-DM patients. This study has reported a no significant association between alcohol consumption and prevalence of diabetes, compared to non-diabetic TB patients who have not been contradicted to the study of Puducherry[13] and Rewa.[21] Like the current study, most of the studies have demonstrated a higher association of diabetes with sputum positivity.[23],[24] In the present study, PTB was considered the most common form found in DM patients, whereas in non-diabetics extrapulmonary TB was more common. The increased association of DM with PTB rather than extrapulmonary TB was also reported previously,[25] indicating that the presence of DM continues to play an important role in the development of PTB. In extrapulmonary TB, pleural effusion was the most common form of extrapulmonary found in both groups and it is not similar to other study where whereas lymph node involvement was the predominant site in extrapulmonary TB.[26]

Diabetes is the strongest risk factor for TB and interferes markedly with the clinical presentation of TB causing more extra-pulmonary and disseminated forms of TB. Despite a higher prevalence of diabetes among TB no interaction was found between TB infection and diabetes in relation to the manifestations of TB. Because this study was conducted in a TB DOT center co-infected with diabetes, it is encouraging that we did not experience a worsened clinical status among patients with both diabetes and TB co-morbidity. However, the nature of the cross-sectional data does not allow commenting on prognosis, because diabetes individually impairs treatment outcome of TB, the combination of diabetes co-morbidity may further worsen TB treatment outcome.[27] Although some epidemiological features of pulmonary TB such as gender, age and residential area are similar in both diabetic and non-diabetic patients, but in clinical point of view, radiological and clinical features were more dominant in diabetic TB-infected patients comparing with non-diabetics patients. In dealing with patients suspected of having TB, these differences should be considered. These results are consistent with other studies.[12],[13],[17],[28],[29] The present study revealed that haemoptysis, lymph node enlargement, chest pain, backache, neck stiffness, motor/sensory deficit and skin nodules in diabetic patients are the more or less same in non-diabetic patients, but a cough, fever, shortness of breath, chronic abdominal pain, fatigue/weakness and other non-specific symptoms are observed in the diabetics more frequent than in non-diabetics and these findings are somewhat similar to Baghaei et al.,[30] who has demonstrated that anorexia, dyspnea and haemoptysis in diabetes were higher than in non-diabetes but, a cough and sputum production in both groups were similar. In general, the results of the clinical findings in this study are concordant to the results of other studies conducted in other regions.[13],[20],[21] It seems that DM patients, because of diabetes-induced immunodeficiency, are incapable of inhibiting the progression to disease, therefore, disease progress more rapidly and the blood vessel wall and pleural involvement results in haemoptysis and dyspnea and TB in older people with weak immunity is associated with less cough and fever in compare with younger individuals while, pleural effusion and cavitations are more common in patients with normal immune responses. These results are in agreement with previous studies in medical literature.[31],[32],[33]

TB and DM are two diseases that are individually relatively common and of immense public health significance globally. Their association and consequences are well established.[18],[22],[23] The study provides new evidence of this association from the 2nd most populous country of the world. The results of this study highlight the importance of screening for DM in TB, which hitherto had not been done. Several recent reports indicate the need to consider the increasing trend in prevalence of diabetes in countries like India, which will impact the TB burden as well.[2],[18] Considering the growing trend in prevalence of diabetes and the huge burden of latent TB infection among Indian population, it is necessary to focus on diagnosis of latent TB infection and screening for DM and ensuring good metabolic control among those diagnosed with DM. The role of possible chemoprophylaxis for subjects with DM and latent TB needs to be carefully considered and evaluated given the magnitude of the burden.[13] With the demographic transition underway globally, increase in life expectancy, improvements in provision of health services and a subsequent increase in the elderly population; the absolute numbers of cases of diabetes will increase exponentially,[34] and The WHO-IUALTD collaborative framework suggests that the type of screening and diagnostic tests for DM in TB patients should be adapted to the context of local health systems and the availability of resources.[35]

  Conclusions Top

This converging of two epidemics should be a wake-up call for all clinicians and researchers to gear-up to meet the challenge of patients afflicted by TB as well as diabetes. It is time that the 'unhealthy partnership' of TB and diabetes receives the attention it deserves.

According to the results of this study, in approach to every DM case presenting with respiratory symptoms such as a productive cough, fever, abdominal pain and fatigue in association with pleural effusion, pulmonary TB should be considered at the top of the differential diagnosis list. We chose a broad-spectrum of para-clinical parameters as well as a qualitative morbidity interview to investigate the impact of diabetes on the clinical manifestations of TB. Furthermore, this being a cross-sectional study, we may have failed to show that people with diabetes have a severe clinical presentation of TB because those with severe manifestation died or failed to seek treatment at the hospitals, or were excluded from the study owing to the exclusion criteria about the severe disease. In conclusion, although diabetes is a risk factor for pulmonary TB in an urban Tanzanian population, it does not seem to considerably increase the severity of TB. Being forewarned and prepared gives a better chance of reducing the dual burden of disease of DM and TB.[36] Since diabetes is associated with increased risk of developing active TB and also is a leading factor in deaths during TB treatment, failure after treatment and increased risk of relapse, it becomes increasingly important that early detection and rigorous management of both diabetes and TB is done for the patients'.[23],[24],[25] After substantial progress in the past two decades, diabetes is estimated to be the cause of 15% of present TB cases, mainly because diabetes impairs host defences. Patients with concurrent diabetes suffer worse TB symptoms and treatment outcomes, a higher rate of relapse following TB treatment, and a higher risk of death from TB than patients with TB alone. Treatment of patients affected by both diseases can be challenging, particularly in low-income settings. The rapidly increasing prevalence of diabetes, especially in the low-income and middle-income countries where TB is endemic is threatening to thwart efforts to tackle TB over the next two decades. The limited resources and infrastructure for diabetes prevention and care at the primary setting make it even more necessary that the health resources and infrastructure for TB control should be further strengthened and serve the purpose of promoting prevention, early detection, and treatment of diabetes among TB patients particularly in India to achieve and maintain a cure rate of >85% in new sputum positive patients for TB and 80% of known diabetic individuals at household level maintain 'controlled disease status' by 2025.[37]


We greatly thank the staff and patients of DOT centers where the study was carried out for their kindly cooperation in the research and conducting the studies.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3]

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