|Year : 2019 | Volume
| Issue : 2 | Page : 162-165
HbA1c levels at presentation do not impact the clinical presentation or outcomes in abdominal tuberculosis
Jimil Shah1, Harshal S Mandavdhare1, Naresh Sachdeva2, Kaushal K Prasad1, Harjeet Singh3, Usha Dutta1, Vishal Sharma1
1 Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||14-Jun-2019|
Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Background: The relationship between diabetes mellitus and tuberculosis (TB) has received increasing attention, and diabetes may be associated with poor outcomes in pulmonary TB. Clinical relevance of HbA1c measurement in abdominal TB is unknown. Methods: We did a retrospective study of consecutive patients diagnosed with abdominal TB and treated with antitubercular therapy for 6 months. Patients were categorized as those with normal HbA1c (<5.7%) or those having elevated HbA1c (≥5.7%). The patients' baseline characteristics, their mode of presentation, type of abdominal TB, and their outcomes after treatment were retrieved and compared. Results: Of 84 patients included in the final analysis, the mean age was 35.52 years and 50% were male. While 19 patients had a confirmed diagnosis, 65 patients were diagnosed as probable abdominal TB. Of the 84 patients, 60 patients (71.43%) had a normal HbA1c and 24 patients (28.57%) had an elevated HbA1c. Those with elevated HbA1c were older in age (47.00 ± 13.98 vs. 30.93 ± 13.91; P < 0.001), and there were more males (75.0% vs. 40.0%; P = 0.004) as compared to the normal HbA1c group. However, other parameters such as their presenting features, pattern of abdominal TB, extra-abdominal involvement, outcomes after treatment, and need of intervention (surgery and dilatation) were comparable between both the groups. Conclusion: Presence of prediabetes or diabetes does not seem to impact the clinical presentation or outcomes in patients with abdominal TB.
Keywords: Abdominal, diabetes, extrapulmonary, HbA1c, tuberculosis
|How to cite this article:|
Shah J, Mandavdhare HS, Sachdeva N, Prasad KK, Singh H, Dutta U, Sharma V. HbA1c levels at presentation do not impact the clinical presentation or outcomes in abdominal tuberculosis. Int J Mycobacteriol 2019;8:162-5
|How to cite this URL:|
Shah J, Mandavdhare HS, Sachdeva N, Prasad KK, Singh H, Dutta U, Sharma V. HbA1c levels at presentation do not impact the clinical presentation or outcomes in abdominal tuberculosis. Int J Mycobacteriol [serial online] 2019 [cited 2020 Sep 26];8:162-5. Available from: http://www.ijmyco.org/text.asp?2019/8/2/162/260372
| Introduction|| |
Tuberculosis (TB) is one of the most important infectious diseases in India with an incidence of 2.79 million new cases every year. Increase in HIV/AIDS or increasing use of various immunosuppressive drugs and biological therapies in various diseases is associated with increased incidence of TB. Diabetes mellitus (DM) is one of the leading noncommunicable diseases. The incidence of DM in India is on rising trend making India the country with the highest number of patients with DM.,
Many studies have shown that patients with DM, especially patients with poor glycemic controls, have a higher risk of developing TB compared to the general population., Studies have also found a higher prevalence of undiagnosed DM in patients with TB. Patients with DM, especially patients with poor glycemic control, are having a decrease in cellular immunity with fewer T-lymphocytes. These patients are also associated with reduced Th1-cytokine response like decrease in interleukin-1β (IL-1β) and IL-6, which is an important defense mechanism in the inhibition of Mycobacterium tuberculosis., Moreover, hyperglycemia is also associated with an impairment of chemotactic and phagocytic function of macrophage and causes impairment of respiratory burst in neutrophils., These factors increase the risk of TB in patients with DM.
Presence of DM is also associated with difference in presentation, type, and severity of TB. Some studies have shown that patients with DM are associated with less cavitation, more extrapulmonary involvement, and increased mortality compared to patients without DM. Studies have shown that patients with DM are associated with more chances of adverse drug reaction and more chances of recurrence of TB even after treatment., Among extrapulmonary TB (EPTB), patients with DM are at higher risk of tubercular peritonitis and more likely to be associated with increased bilirubin levels.
Abdominal TB is an important cause of EPTB accounting for 12.8% of all EPTBs. Although many studies have shown the effect of DM on presentation and outcome in patients with pulmonary TB, the effect of DM in patients with EPTB has shown inconsistent results. Moreover, no studies have been done until now to know the effect of DM on presentation and treatment response in patients with abdominal TB. Therefore, we studied the effect of elevated HbA1c and DM on mode of presentation and treatment outcome in patients with abdominal TB.
| Methods|| |
The retrospective study was conducted at tertiary care center in North India. Consecutive patients with abdominal TB either enrolled in gastroenterology outpatient department or admitted in the ward between 2016 and 2017 were included. Patients with abdominal TB were divided into visceral TB, lymph nodal TB, peritoneal TB, or luminal (intestinal) TB. Informed consent was obtained from all patients before undergoing any invasive procedure (colonoscopy and ascitic fluid paracentesis).
Diagnosis of abdominal TB was done as per the standard criteria. Patients were considered as confirmed case in the presence of acid-fast bacilli (AFB) on smear or positivity of appropriate PCR or GeneXpert test or presence of caseating granulomas. Other cases were considered as “clinically diagnosed case” if these tests are negative, but clinical history and examination, laboratory investigations (adenosine deaminase), radiology, and/or histology (granuloma without caseation) are suggestive of TB after exclusion of other conditions.
Patients with confirmed or clinically diagnosed abdominal TB were treated with antitubercular therapy (ATT) for 6 months. All baseline data including their mode of presentation, baseline investigations, and type of abdominal TB were recorded. After starting treatment, all patients were closely followed till the end of therapy. Patients' response to treatment was checked clinically in the form of weight gain, fever defervescence, resolution of abdominal pain, or distension, etc., In patients with intestinal TB, colonoscopy was repeated after 2 months of ATT to see for early mucosal response. In the presence of peritoneal TB, periodic ultrasound abdomen was done to see for the resolution of ascites. Development of ATT-induced hepatitis, requirement of surgery, and requirement of dilatation in case of intestinal TB were also recorded.
All the data were entered in Microsoft Excel format and then exported to SPSS Version 23 (SPSS Inc., Chicago, IL, USA). Data were represented as mean ± standard deviation or median and interquartile range if they had a nonparametric distribution. Continuous variables were compared using Student's t-test. Discrete variables were analyzed by Chi-square test and Fisher's exact test. A two-tailed P < 0.05 was considered to be statistically significant in all statistical evaluations.
| Results|| |
A total of 84 patients of abdominal TB were included in this study. The mean age of patients in the study group was 35.52 (14–80) years and 42 patients (50%) were male. Patients were divided into two groups: patients with HbA1c <5.7 (Group A, n = 60; 71.4%) and patients with HbA1c ≥5.7 (Group B, n = 24; 28.6%). Patients in Group B were more likely to be of older age (47.00 ± 13.98 vs. 30.93 ± 13.91; P < 0.001) compared to Group A. Males were more common in Group B compared to Group A (75.0% vs. 40.0%; P = 0.004). However, patients in both the groups were comparable in their presenting complaints including the presence of abdominal pain, fever, loss of weight, and symptoms of intestinal obstruction [Table 1].
|Table 1: Baseline characteristics and presenting complaints of the study population|
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Patients in Group B were more likely to have higher hemoglobin (11.92 ± 2.73 vs. 10.84 ± 1.89; P = 0.04) and higher HbA1c compared to Group A (6.57 ± 1.48 vs. 5.02 ± 0.46; P < 0.001) [Table 2]. Both the groups were comparable in other parameters including total leukocyte count, platelets, C-reactive protein (CRP), and albumin levels [Table 2]. Mantoux test positivity was also comparable between both the groups (58.33% vs. 50.0%; P = 0.424).
In both the groups, the most common site of abdominal TB was intestinal (48.33% and 45.83% in Group A and B, respectively) followed by peritoneal (30.0% vs. 41.67% in Group A and B, respectively). Other locations of TB were either lymph nodal, hepatic, or combined peritoneal and intestinal [Table 3]. In both the groups, the distribution of TB was comparable (P = 0.262) [Table 3]. Nineteen patients (31.7%) in Group A and seven patients (29.17%) in Group B were having simultaneous extra-abdominal TB (P = 0.823). Diagnosis was of “confirmed TB” in 22.3% of the patients in Group A and 20.8% of the patients with Group B (P = 0.805). Rest of the patients were “clinically diagnosed cases” according to the definition. However, these patients were followed after ATT course and their response to ATT was also confirmed.
At the end of ATT, 58 (96.67%) patients improved in Group A and all patients improved in Group B (P = 0.349) [Table 4]. One patient in Group A stopped ATT and was lost to follow-up and one patient worsened on ATT requiring surgery. At 6 months, 5% of the patients in Group A and 4.17% of the patients in Group B developed ATT-induced hepatitis (P = 0.871). In Group A, five patients (8.33%) required surgery and one (1.67%) patient required dilatation due to intestinal stricture during ATT. In Group B, two (8.33%) patients required surgery and one (4.17%) patient required percutaneous catheter drainage of ascites during ATT [Table 4].
|Table 4: Outcome in patients with antitubercular therapy between the two groups|
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| Discussion|| |
In this study, we have compared the effect of elevated HbA1c and diabetes on presentation and outcome of treatment in patients with abdominal TB. We have found that apart from increased age and increased prevalence of male patients in patients with elevated HbA1c, patients in both the groups had a similar type of presentation, distribution, and response to treatment.
DM and TB both are important causes for morbidity and mortality in India. Prevalence of DM in patients with TB varies between 9% and 15% in different studies. It is very important to understand the interactions between these diseases, as studies have shown that patients with DM are associated with increased risk of active, sputum-positive pulmonary TB. The risk is higher in patients with HbA1c ≥7.0 compared to patients with HbA1c <7.0. These patients are also at increased risk of sputum positivity at 2 months and poorer outcome in patients with pulmonary TB.
Although these interactions of DM with TB are well-documented in patients with pulmonary TB, their interaction in patients with EPTB is not well established. Moreover, diagnosis and treatment follow-up in patients with EPTB are more complicated than pulmonary TB due to less smear-positive-confirmed cases and more reliance on clinical history, ancillary laboratory investigations, and histology. We have studied 84 cases of abdominal TB. In this study, one-third of the patients had HbA1c ≥5.7 which is comparable to older studies on TB. These patients were elder compared to patients with HbA1c <5.7, which may due to more prevalence of type 2 DM. Patients in both the groups had a similar type of presenting complaints including abdominal pain, fever, symptoms suggestive of intestinal obstruction, and loss of weight. A study by Carreira et al. demonstrated that the presentation of TB was similar between DM and non-DM population. In this study, both the groups were having similar rates of Mantoux test positivity, which is contrary to an initial report by Nwabudike and Ionescu-Tîrgovişte, in which they showed impaired response to PPD during acute hyperglycemia. In the present study, patients had good glycemic control with the mean HbA1c of 6.57 ± 1.48. This might be the reason for preserved Mantoux reaction in these patients. Rest other investigations including CRP and albumin were comparable between the two groups.
Distribution of abdominal TB in patients with elevated HbA1c was also similar to other patients. Intestinal type of TB followed by peritoneal TB was the most common type of TB in both the groups accounting for almost three-fourth of the cases. In this study, concurrent extra-abdominal TB was present in one-third of the cases in both the groups. Hyperglycemia was not associated with different distributions of abdominal TB or increased risk of disseminated TB. In a study by Weng et al., tubercular peritonitis was more common among all EPTBs in patients with DM. After treatment at 6 months, patients in both the groups showed >95% improvement with treatment. Drug-resistant TB, which is the major challenge in patients with pulmonary TB, is rare in patients with intestinal or peritoneal TB., These factors might be the reason for good response to ATT in this study. In this study, patients in both the groups had a similar rate of complications including need of surgery and ATT-induced hepatitis.
The present study shows that the effect of elevated HbA1c and DM on presentation and treatment outcome in patients of abdominal TB is minimal. We have followed these patients till the end of therapy to know side effects, improvement after therapy, and failure of therapy.
There are few limitations in this study. Confirmed cases of abdominal TB were only 20% in both the groups. Previous studies have also shown low yield of smear for AFB in abdominal TB being it a paucibacillary disease., Hence, the diagnosis of abdominal TB mainly relies on clinical history, laboratory tests, histological examination, and response to treatment. In this study, the median HbA1c is lower even in Group B with the mean of 6.57 which might be a reason for nondifference in outcome between the two groups, as previous studies have shown poorer outcome in patients with HbA1c >7.,, This might require a larger multicenter study, with different HbA1c levels to know their effects on treatment outcome.
| Conclusion|| |
Patients with prediabetes or diabetes do not differ in their presentation or pattern of involvement in abdominal TB. Patients with prediabetes or diabetes respond well to ATT, and they are not associated with increased risk of complications.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Francis NK, Pawar HS, Mitra A, Mitra A. Rising trend of diabetes mellitus amongst the undernourished: State -of- the -art review. Diabetes Metab Syndr 2017;11 Suppl 1:S169-74.
Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India. Australas Med J 2014;7:45-8.
Leung CC, Lam TH, Chan WM, Yew WW, Ho KS, Leung GM, et al.
Diabetic control and risk of tuberculosis: A cohort study. Am J Epidemiol 2008;167:1486-94.
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]
Irfan M, Salahuddin N, Masood Q, Ahmed O, Moosajee US, Hasan Z. Assessment of diabetes among tuberculosis patients presenting at a tertiary care facility in Pakistan. Int J Mycobacteriol 2016;5 Suppl 1:S248.
Moutschen MP, Scheen AJ, Lefebvre PJ. Impaired immune responses in diabetes mellitus: Analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections. Diabete Metab 1992;18:187-201.
Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol 1999;26:259-65.
Carreira S, Costeira J, Gomes C, André JM, Diogo N. Impact of diabetes on the presenting features of tuberculosis in hospitalized patients. Rev Port Pneumol 2012;18:239-43.
Wang JY, Lee MC, Shu CC, Lee CH, Lee LN, Chao KM, et al.
Optimal duration of anti-TB treatment in patients with diabetes: Nine or six months? Chest 2015;147:520-8.
Siddiqui AN, Khayyam KU, Sharma M. Effect of diabetes mellitus on tuberculosis treatment outcome and adverse reactions in patients receiving directly observed treatment strategy in India: A prospective study. Biomed Res Int 2016;2016:7273935.
Weng SF, Hsu CH, Lirn ML, Huang CL. Extrapulmonary tuberculosis: A study comparing diabetic and nondiabetic patients. Exp Clin Endocrinol Diabetes 2009;117:305-7.
Cherian JJ, Lobo I, Sukhlecha A, Chawan U, Kshirsagar NA, Nair BL, et al.
Treatment outcome of extrapulmonary tuberculosis under revised national tuberculosis control programme. Indian J Tuberc 2017;64:104-8.
Sharma SK, Ryan H, Khaparde S, Sachdeva KS, Singh AD, Mohan A, et al.
Index-TB guidelines: Guidelines on extrapulmonary tuberculosis for India. Indian J Med Res 2017;145:448-63.
] [Full text]
Sharma V, Debi U, Mandavdhare HS, Prasad KK. Abdominal tuberculosis and other mycobacterial infections. Ref Module Biomed Sci 2018. [doi.org/10.1016/B978-0-12-801238-3.65963-9].
Sharma V, Mandavdhare HS, Dutta U. Letter: Mucosal response in discriminating intestinal tuberculosis from Crohn's disease-when to look for it? Aliment Pharmacol Ther 2018;47:859-60.
Sharma V, Mandavdhare HS, Lamoria S, Singh H, Kumar A. Serial C-reactive protein measurements in patients treated for suspected abdominal tuberculosis. Dig Liver Dis 2018;50:559-62.
Nwabudike LC, Ionescu-Tîrgovişte C. Intradermal reactions to purified protein derivative in patients with diabetes mellitus. Rom J Intern Med 2005;43:127-32.
Ye BD, Yang SK, Kim D, Shim TS, Kim SH, Kim MN, et al.
Diagnostic sensitivity of culture and drug resistance patterns in Korean patients with intestinal tuberculosis. Int J Tuberc Lung Dis 2012;16:799-804.
Chaudhry LA, Essa EB, Al-Solaiman S, Al-Sindi K. Prevalence of diabetes type-2 & pulmonary tuberculosis among Filipino and treatment outcomes: A surveillance study in the Eastern Saudi Arabia. Int J Mycobacteriol 2012;1:106-9. [Full text]
[Table 1], [Table 2], [Table 3], [Table 4]