|Year : 2021 | Volume
| Issue : 2 | Page : 111-115
Treatment outcomes of patients with tuberculosis and diabetes: A prospective cohort study from India
Ananya Desai1, Nitin Gupta2, Lakshmi Korishetty3, Kavitha Saravu2
1 Department of 1Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Infectious Diseases, Kasturba Medical College, Manipal Academy of Higher Education; Manipal Center for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
|Date of Submission||21-Jan-2021|
|Date of Acceptance||24-Feb-2021|
|Date of Web Publication||14-Jun-2021|
Department of Infectious Diseases, Kasturba Medical College, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Tuberculosis (TB) and diabetes mellitus (DM) are significant causes of morbidity and mortality in developing countries. This study aimed to explore the relationship between diabetes and TB. Methods: This was a prospective cohort study in which all newly diagnosed inpatients with TB above the age of 18 years during the study period (September 2018 to August 2020) were included. Fasting sugars and glycosylated hemoglobin (HbA1c) levels were recorded at the baseline, 3rd month, and 6th month in the diabetic patients on antitubercular therapy (ATT). Treatment outcomes were measured in both the diabetic and the nondiabetic groups. Results: The prevalence of diabetes in patients with TB admitted at our tertiary care hospital was found to be 38.5%. A favorable treatment outcome was seen in 96.3% of the patients with DM when compared to 95.6% in those without diabetes. A decreasing trend of HbA1c and fasting sugars was noticed in patients with DM during ATT. Conclusion: The screening of DM in patients with TB can help in early diagnosis and better glycemic control which may improve the possibility of favorable outcomes.
Keywords: Diabetes mellitus, extrapulmonary, fasting glucose, glycosylated hemoglobin, pulmonary
|How to cite this article:|
Desai A, Gupta N, Korishetty L, Saravu K. Treatment outcomes of patients with tuberculosis and diabetes: A prospective cohort study from India. Int J Mycobacteriol 2021;10:111-5
|How to cite this URL:|
Desai A, Gupta N, Korishetty L, Saravu K. Treatment outcomes of patients with tuberculosis and diabetes: A prospective cohort study from India. Int J Mycobacteriol [serial online] 2021 [cited 2022 Sep 27];10:111-5. Available from: https://www.ijmyco.org/text.asp?2021/10/2/111/307069
| Introduction|| |
The worldwide prevalence of diabetes mellitus (DM) is enormous, and by the year 2030, it is expected to increase up to 550 million. According to a report, there are 463_million people with DM in the world with 88 million located in the South-East Asian regions. India is currently home to nearly one-third of global tuberculosis (TB) burden with 77 million people diagnosed with diabetes. DM, being an immune-compromised state, has been identified as a major risk factor for many infectious diseases, including TB and mucormycosis., In diabetic patients, infections such as TB usually worsen the glycemic control, and uncontrolled diabetes invariably enhances the gravity of the infection. TB, among other infections, can cause impairment of glucose control and predisposes patients to DM. In a country like India, where the dual burden of both these diseases is high, the interaction among them becomes a major challenge to the health system. The objectives of the study were to determine the prevalence of DM in TB patients, to determine the treatment outcomes of TB patients with DM, and to estimate the trends of glycosylated hemoglobin (HbA1c) levels in patients with TB and DM on antitubercular therapy (ATT).
| Methods|| |
A prospective study was conducted at Kasturba Hospital, a tertiary care hospital in the southern part of India. All hospitalized adult patients >18 years with newly diagnosed with pulmonary TB (PTB) and extrapulmonary tuberculosis (EPTB) between September 2018 to August 2020 were included in the study. Those patients who have been already started on ATT for >15 days were excluded from the study. A case was considered as PTB if the sputum of the patient tested positive for acid-fast bacillus staining, cartridge-based nucleic acid testing, or culture. A case was considered EPTB if there were clinical, radiological, and pathological features suggestive of tubercular involvement of sites other than the lung. Patients were considered as diabetic if they had a fasting plasma glucose (FBS) >126 mg/dl or HbA1c >6.5% at the time of diagnosis. Both newly diagnosed diabetics and those on treatment were included.
A brief clinical history and the underlying comorbid conditions of patients satisfying the inclusion criteria were obtained. Clinical parameters, such as height, weight, and body mass index (BMI), were noted. The method for diagnosis of TB was recorded in all patients. The baseline investigations of FBS and HbA1c levels were recorded for all patients. The patients were followed up for a response to ATT. A case was considered “cured” if the positive sputum smear or culture became negative by the end of treatment. A case was considered “treatment completed” if the treatment was completed and there was no clinical evidence of failure but in whom microbiological evidence of cure could not be obtained. A “defaulter” was a patient whose treatment was interrupted for 2 consecutive months while “treatment failure” was defined as persistent positivity of sputum smear or culture at 5 months. A case was considered as lost to follow-up if one failed to follow up after initiation of treatment. “Cured” and “treatment completed” were considered as “favorable outcome” while the rest were considered as “unfavorable outcome.” The trend of FBS and HbA1c levels was also charted by measuring them on the 3rd and 6th months in diabetics.
The data analysis was done using Excel and IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA). Those variables with normal distribution were expressed as mean ± standard deviation), and the baseline characteristics of the population were compared by Chi-square/Fisher's exact test. Post hoc analysis was done to compare pairwise time point, and Mann–Whitney U-test was used to compare HbA1c levels in the PTB and EPTB groups.
| Results|| |
A total of 286 patients who were newly diagnosed with TB at our hospital during the study period were enrolled consecutively. A total of 172 (60.1%) patients had PTB, and 114 (39.9%) patients had EPTB. In EPTB, pleural effusion (34%) was most common followed by lymphadenitis (19%), abdominal TB (17%), musculoskeletal TB (12.2%), neurological TB (10.5%), genitourinary TB (3.5%), and TB pericarditis (2.6%).
Out of the 286 patients, 110 patients (38.5%) had DM. Out of the 110 patients who were diabetics, 80.9% (89) patients had a known history of diabetes, and 19.1% (21) were newly diagnosed diabetics. The mean duration of the history of diabetes was 6.2 ± 1.89 years. A total of 41 (37.3%) patients required insulin treatment and 69 (62.7%) patients were only on oral antidiabetics. In patients with DM, baseline HbA1c ranged between 5.7% and 15% with the majority of the patients having HbA1c between 7.2% and 11.05%. The median HbA1c at baseline in diabetics was 9.19 (interquartile range [IQR] = 7.2%–11%). HbA1c among patients without DM in the study cohort ranged between 4.4% and 6.4% with the majority of the patients having HbA1c between 5.2% and 5.8%. The median HbA1c at baseline in nondiabetics was 5.43 (IQR = 5.2%–5.8%).
The baseline characteristics and method of diagnosing TB patients with diabetes and nondiabetics are summarized in [Table 1]. PTB was more common in diabetics when compared to nondiabetics [Table 1]. DM was more prevalent in TB patients in the age group of 41–60 years with a mean age of 45.2 years ± 0.8 [Table 1]. There was a higher prevalence of TB-DM among males than females [Table 1]. There was no significant difference in the BMI between diabetics and nondiabetics [Table 1]. History of smoking and alcohol was more commonly seen in diabetics [Table 1]. History of ischemic heart disease was more common in diabetics [Table 1].
|Table 1: Baseline characteristics of tuberculosis patients with and without diabetes mellitus|
Click here to view
Out of the 286 patients, a total of 173 patients (60.5%) were followed up at our hospital. The rest of the patients chose to continue their treatment at a nearby government center of Directly Observed Treatment Short-Course (DOTS) Chemotherapy. Their follow-up details are not available. The treatment outcomes of TB patients with and without DM are summarized in [Table 2].
|Table 2: Treatment outcomes in tuberculosis patients with and without diabetes mellitus|
Click here to view
The mean FBS for PTB and EPTB patients at baseline was 200.3 ± 92.6 and 158.6 ± 60.8, respectively. The mean HbA1c for PTB and EPTB patients at baseline was 9.5 ± 2.3 and 8.3 ± 2, respectively. The FBS and HbA1c in diabetic patients (both PTB and EPTB) on ATT showed a decreasing trend on follow-up at the 3rd and the 6th months. The mean change in FBS and HbA1c was found to be significantly higher in the PTB group when compared to the EPTB group [Table 3].
|Table 3: Trends of fasting blood sugar and glycosylated hemoglobin in tuberculosis patiens with diabetes mellitus|
Click here to view
| Discussion|| |
Although the association between TB and DM was suggested for long, the recognition of this dual epidemic has come to light only recently. DM is a chronic disease with hyperglycemia resulting in oxidative stress and tissue damage as well as impairment in immunity, predisposing individuals to TB. TB, on the other hand, has been observed to cause disruption of glycemic control, thereby predisposing to DM. The World Health Organization has, therefore, recommended for bidirectional screening to tackle this looming epidemic of diabetes and TB.
Our cohort included admitted patients who were newly diagnosed with TB. It was observed that TB patients with DM were predominantly male and between the age group of 41 and 50 years, similar to other studies from India.,, A study from Nigeria also showed that males are generally reported to have a higher risk of TB-DM than females. This could be due to a higher prevalence of smoking and alcohol intake in males. In our study, history of smoking and alcohol was more commonly found in diabetics when compared to nondiabetics. Some of the previous studies have shown a significantly higher BMI in diabetic patients with TB when compared to nondiabetics. In contrast, Kumpatla et al. reported a lower mean BMI in the TB-DM group as compared to nondiabetics with TB. Few other studies, similar to our study, have shown that no significant correlation was found between BMI and TB-DM.
Our study cohort showed a higher prevalence of DM at 38.5%, which could be due to the possible selection bias as only hospitalized patients were included. Previous studies have shown that hospitalized TB patients have a significantly higher prevalence of DM compared to patients receiving outpatient care., Other studies done from India have shown an estimated prevalence of DM in TB varying between 19.2% and 32.2%.,, In our study, PTB was more common in diabetics compared to nondiabetics. Previous studies conducted in India, Brazil, the United States of America, and China have shown similar results. A credible mechanism explaining this particular association has not yet been adequately described.
In a systematic review done by Baker et al., it was observed that treatment outcomes were poor in diabetics. In a study from Malaysia, DM was found to be a significant risk factor for persistence of sputum positivity in the 2nd month of treatment. In a study from Dubai, DM was found to be a risk factor of TB drug resistance as well. However, in a study done in Kerala, India, there was no statistical significance observed between the treatment outcomes in TB patients with and without DM. In our study, the treatment outcomes of TB were comparable between the diabetics and nondiabetics. This could have been because the study was conducted in a tertiary care hospital where quality care was available for the patients, and good follow-up was ensured.
Glycemic control plays an important role in determining the prognosis of TB treatment. The mean HbA1c levels and FBS showed a decreasing trend on follow-up in most patients. Similar findings have been noticed in other studies as well., The change was more pronounced in PTB patients when compared to EPTB. This could have been because of the higher baseline levels of FBS and HbA1C in PTB patients compared to EPTB patients. There were seven patients with an unfavorable response in this study. Out of these seven, six died during the first admission, and therefore, their follow-up could not be done. Since the number of patients with an unfavorable response to ATT was very less and follow-up could not be done due to early death, the trend of sugars and HbA1c between those with the favorable and unfavorable response could not be compared.
The follow-up details of 113 patients were not available as they chose to follow up with the government DOTS center.
| Conclusion|| |
The prevalence of DM in patients with TB is high, especially in patients with PTB. The treatment outcomes with ATT were observed to be comparable in patients with diabetic and nondiabetic cohorts. The screening of DM in patients with TB can help in early diagnosis and better glycemic control which may improve the possibility of favorable outcomes.
Ethical clearance was obtained prior to the study. IEC number: 645/2018 (Date 10th October 2018).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Harries AD, Satyanarayana S, Kumar AM, Nagaraja SB, Isaakidis P, Malhotra S, et al
. Epidemiology and interaction of diabetes mellitus and tuberculosis and challenges for care: A review. Public Health Action 2013;3 (Suppl 1):S3-9.
Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al
. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th
Edition. Diabetes Res Clin Pract 2019;157:107843.
Ramesh P, Kaur G, Deepak D, Kumar P. Disseminated pulmonary mucormycosis with concomitant tuberculosis infection in a diabetic patient. Int J Mycobacteriol 2020;9:95-7.
] [Full text]
Ahmed M, Omer I, Osman SM, Ahmed-Abakur EH. Association between pulmonary tuberculosis and Type 2 diabetes in Sudanese patients. Int J Mycobacteriol 2017;6:97-101.
] [Full text]
Abdul-Hadi MH, Naji MT, Shams HA, Sami OM, Al-Harchan NA, Al-Kuraishy HM, et al
. Oxidative stress injury and glucolipotoxicity in type 2 diabetes mellitus: The potential role of metformin and sitagliptin. Biomed Biotechnol Res J 2020;4:166-72. [Full text]
Harries AD, Lin Y, Satyanarayana S, Lönnroth K, Li L, Wilson N, et al. The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis. The International Journal of Tuberculosis and Lung Disease. 2011;15:1436-45.
Raghuraman S, Vasudevan KP, Govindarajan S, Chinnakali P, Panigrahi KC. Prevalence of diabetes mellitus among tuberculosis patients in urban Puducherry. N Am J Med Sci 2014;6:30-4.
Hochberg NS, Sarkar S, Horsburgh CR Jr., Knudsen S, Pleskunas J, Sahu S, et al
. Comorbidities in pulmonary tuberculosis cases in Puducherry and Tamil Nadu, India: Opportunities for intervention. PLoS One 2017;12:e0183195.
Kottarath MD, Mavila R, Achuthan V, Nair S. Prevalence of diabetes mellitus in tuberculosis patients: a hospital based study. Int J Res Med Sci 2017;3:2810-4.
Lawson L, Muc M, Oladimeji O, Iweha C, Opoola B, Abdurhaman ST, et al
. Tuberculosis and diabetes in Nigerian patients with and without HIV. Int J Infect Dis 2017;61:121-5.
Kumpatla S, Sekar A, Achanta S, Sharath BN, Kumar AM, Harries AD, et al
. Characteristics of patients with diabetes screened for tuberculosis in a tertiary care hospital in South India. Public Health Action 2013;3:S23-8.
Pande T, Huddart S, Xavier W, Kulavalli S, Chen T, Pai M, et al
. Prevalence of diabetes mellitus amongst hospitalized tuberculosis patients at an Indian tertiary care center: A descriptive analysis. PLoS One 2018;13:e0200838.
Li L, Lin Y, Mi F, Tan S, Liang B, Guo C, et al
. Screening of patients with tuberculosis for diabetes mellitus in China. Trop Med Int Health 2012;17:1294-301.
Viswanathan V, Kumpatla S, Aravindalochanan V, Rajan R, Chinnasamy C, Srinivasan R, et al
. Prevalence of diabetes and pre-diabetes and associated risk factors among tuberculosis patients in India. PLoS One 2012;7:e41367.
Ratre BK, Shrivastava AK, Patel NP, Jain R, Raghuvanshi P, Singh DP, et al
. Prevalence of diabetes mellitus in tuberculosis patient: A tertiary care centre study from Central India. J Evol Med Dent Sci 2014;3:8155-61.
Reis-Santos B, Locatelli R, Horta BL, Faerstein E, Sanchez MN, Riley LW, et al
. Socio-demographic and clinical differences in subjects with tuberculosis with and without diabetes mellitus in Brazil – A multivariate analysis. PLoS One 2013;8:e62604.
Mi F, Tan S, Liang L, Harries AD, Hinderaker SG, Lin Y, et al
. Diabetes mellitus and tuberculosis: Pattern of tuberculosis, two-month smear conversion and treatment outcomes in Guangzhou, China. Trop Med Int Health 2013;18:1379-85.
Baker MA, Harries AD, Jeon CY, Hart JE, Kapur A, Lönnroth K, et al
. The impact of diabetes on tuberculosis treatment outcomes: A systematic review. BMC Med 2011;9:81.
Shariff NM, Safian N. Diabetes mellitus and its influence on sputum smear positivity at the 2nd
month of treatment among pulmonary tuberculosis patients in Kuala Lumpur, Malaysia: A case control study. Int J Mycobacteriol 2015;4:323-9. [Full text]
Habous M, Elimam M, AlDabal L, Chidambaran B, AlDeesi Z. Pattern of primary tuberculosis drug resistance and associated risk factors at Dubai health authority in Dubai. Int J Mycobacteriol 2020;9:391-6.
] [Full text]
Nandakumar KV, Duraisamy K, Balakrishnan S, Sunilkumar M, Jaya Sankar S, Sagili KD, et al
. Outcome of tuberculosis treatment in patients with diabetes mellitus treated in the revised national tuberculosis control programme in Malappuram District, Kerala, India. PLoS One 2013;8:e76275.
Gupte AN, Mave V, Meshram S, Lokhande R, Kadam D, Dharmshale S, et al
. Trends in HbA1c levels and implications for diabetes screening in tuberculosis cases undergoing treatment in India. Int J Tuberc Lung Dis 2018;22:800-6.
Boillat-Blanco N, Ramaiya KL, Mganga M, Minja LT, Bovet P, Schindler C, et al
. Transient hyperglycemia in patients with tuberculosis in Tanzania: Implications for diabetes screening algorithms. J Infect Dis 2016;213:1163-72.
[Table 1], [Table 2], [Table 3]