Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is associated with diffuse functional impairment of most endocrine organs resulted in diffuse endocrinopathies. As any chronic infection, like TB is also associated with hyperglycemia1. TB is the leading cause of death due to an infective disease in the world2. The global incidence of TB cases reached 10.8 million in 2023, with the majority occurring in the WHO regions of South-East Asia (45%), Africa (24%), and the Western Pacific (17%), marking a stabilization after a rise during the COVID-19 pandemic3. Diabetes Mellitus (DM), a chronic condition of impaired insulin production or use, triples the risk of developing tuberculosis (TB) due to elevated blood glucose levels4-9. The global prevalence of diabetes in adults (20–79 years) has tripled since 2000, reaching 537.5 million (10.5%) in 2021 and is projected to exceed 12.8% by 2045, with the increase being more pronounced in low- and middle-income countries compared to high-income nations. 

Southeast Asia and India saw prevalence rates of 8.8% and 9.6% in 2021, expected to rise to 11.5% and 10.9%, respectively, by 204510. According to WHO, non-communicable diseases constitute 7 out of the top 10 leading causes of death and DM is prominent among them.DM is associated with significant morbidity due to its microvascular and macrovascular complications and high cardio vascular mortality. DM is a major cause of cardiac ischemia, stroke, renal failure, blindness, and amputations11. Tuberculosis (TB) and diabetes mellitus (DM) are major public health challenges, with TB linked to poverty and DM spanning all socio-economic groups, increasingly prevalent in low- and middle-income countries. The rise in DM cases worsens the TB epidemic, as both conditions collaboratively exacerbate morbidity and mortality despite medical advancements12. HemoglobinA1c (HbA1c) is the glycated form of haemoglobin and is regarded as an average level of glucose during the past 90 days13-14. Studies reveal a strong link between HbA1c levels and type 2 diabetes prevalence, with uncontrolled diabetes (HbA1c ≥7) posing a higher risk for delayed sputum culture conversion in TB patients and greater positive culture rates at treatment completion compared to non-diabetic patients.The efficacy of anti-TB treatment is evaluated by Time to Disappearance (Td), marking the period from treatment initiation to three consecutive negative sputum cultures, with good responders achieving culture negativity within 30 days and poor responders remaining positive despite standard therapy15. The sputum conversion rate (SCR) measures the percentage of smear-positive TB cases that become smear-negative after two months of intensive treatment, serving as a key indicator of TB program performance and a predictor of therapy success, with conversion influenced by factors like adherence, nutrition, and lifestyle16,17.

Aim

To Study the association between Haemoglobin A1c Levels and Sputum Conversion Time by LED microscopy in patients of smear positive Pulmonary Tuberculosis.

This hospital-based prospective study was conducted in the Department of Respiratory Medicine, Sardar Patel Medical College, Bikaner, Rajasthan, over six months (January 2024 to June 2024). A sample size of 120 cases was determined using the formula \(4pq/d^2\), with an assumed diabetes prevalence of 18% among TB patients, as per Laxmi SB et al. (2019). The study included patients consecutively enrolled from the OPD and IPD of the department, using consecutive sampling. Approval was obtained from the Ethical Committee and Research Review Board of S.P. Medical College, Bikaner. The inclusion criteria comprised new smear-positive pulmonary TB cases under DOTS, patients aged 18 years and above of either sex, those with pre-existing or newly diagnosed diabetes mellitus, and patients without diabetes willing to participate. Exclusion criteria included recurrent pulmonary TB cases, suspected or confirmed multi-drug-resistant TB, HIV-positive patients, those unable to tolerate DOTS, and patients unwilling to participate.

Table-1: Distribution of patients according to their age group

Table 1 shows distribution of patients according to their age group. Maximum 50% were in 41-60 years group followed by 61-80 years 30.00% whereas minimum 0.83% were in >80 years age group followed by 0-20 years 3.33%. Mean age of study population was observed 51.60 ± 14.19 years.

Graph 1: Distribution of patients according to their occurrence of chief complaints

Graph shows distribution of patients according to their chief complaints. 95.83% patients had Cough with expectoration and 93.33% had fever followed by 80% had weight loss, 65.83% had loss of appetite, 56.67% had night sweats and minimum 15.83% had shortness of breath, 19.17% had chest pain, and 22.50% had hemoptysis.

Table-2: Distribution of patients according to their personal habits

Table 2 shows distribution of patients according to their personal habits.

Maximum 61.67% were smoker and 22.50% were alcoholic.

Table-3: Distribution of patients according to Anthropometric parameters

Table 3 shows distribution of patients according to Anthropometric parameters. Mean of weight was 49.77±7.73 kg, mean height was 1.62 ± 0.51 m.

Graph 2: Distribution of patients according to infiltration in chest X Ray

Graph shows distribution of patients according to infiltration in chest X Ray. Majority 35.83% had right upper lobe followed by 26.67% in bilateral upper lobe, 13.33% had right upper and left lower lobe whereas minimum 4.17% had right middle lobe, 5% had left upper lobe, 6.67% had right lower and left upper lobe and 8.33% had Right upper lobe and right middle lobe involvement.   

Table 4: Distribution of patients according to their history of diabetes

Table 4 shows distribution of patients according to their history of diabetes. Majority 30.00% were known case of diabetes and 3.33% were newly diagnosed case whereas 66.67% dose not had any diabetes.

Table-5: Distribution according to bacteriological grading  at time of diagnosis

Table 5 shows distribution according to bacteriological grading at time of diagnosis. Maximum 41.67% had 1+ grad, 30% had 2+, 25% had 3+ on sputum examination whereas 3.33% had scanty positivity on sputum microscopy test.

Table-6:  Correlation of sputum bacteriological grading with HbA1c level at time of diagnosis

Table 6 shows a statistically significant association between HbA1c levels and sputum bacteriological grading, with higher HbA1c (≥6.5%) correlating with more severe bacteriological positivity (p=0.0001**).

Table-7: Distribution of HbA1c levels on different follow up

Table 7 shows a statistically significant reduction in mean HbA1c levels among TB patients with diabetes from 10.24% pretreatment to 7.05% at 6 months (p=0.0001**), while levels remained stable among non-diabetic TB patients.

Table-8:  Correlation of delayed sputum conversion with HbA1c levels

Table 8 shows association correlation between HbA1c levels & delayed sputum conversion. Maximum 5 (29.41%) cases of delayed sputum conversion had HbA1c level <6.5% and 8 – 10% each followed by >10% HbA1c in 23.53% cases whereas 3 (17.65%) cases had HbA1c 6.5 – 8%.

Table-9:  Correlation of sputum conversion with HbA1c levels at follow up

Table 9 demonstrates a statistically significant association (p=0.001**) between higher HbA1c levels (≥6.5%) and delayed sputum conversion, with 30% delayed at 2 months and 10% at 3 months, compared to 6.25% and 0% in patients with HbA1c <6.5%.

In our study mean age of study population was 51.60 ± 14.19with a minimum age of 19 years and maximum of 83 years. Maximum (50%) of the study population belonged to 41-60 years of age followed by 61-80 years (30.00%) whereas minimum (0.83%) were in >80 years age group.

In this study majority (95.83%) patients had Cough with expectorations and (93.33%) had fever followed by (80%) had weight loss, (65.83%) had loss of appetite, (56.67%) had night sweats and minimum (15.83%) had shortness of breath, (19.17%) had chest pain, and (22.50%) had hemoptysis.

Among 120 subjects Maximum (35.83%) had right upper lobe followed by (26.67%) in bilateral upper lobe, (13.33%) had right upper and left lower lobe whereas minimum (4.17%) had right middle lobe, (5%) had left upper lobe, (6.67%) had right lower and left upper lobe involvement. TB-DM patients had more involvement of lower lobe and presence of cavitation more than consolidation which was in TB without DM. X-Ray lesion in lower lobes involvement with cavities in patients with DM is significantly related.

Among 120 study subjects (33.3%) were diabetics, Majority (30.00%) were known case of diabetes and (3.33%) were newly diagnosed cases. Raghuraman et al (2014)18 studied 51 patients (32.9%) with smear-positive TB patients with T2DM.

In contrast to the above findings, study done in Nigeria by Oliyanka et al (2013) found the prevalence to be 5.7%.55 Maximum (41.67%) subjects had 1+ grading, (30%) had 2+grading, (25%) had 3+ grading on sputum examination whereas (3.33%) had scanty positivity on sputum microscopy test. 

Patients with HbA1c <6.5% maximum (56.25%) had 1+ followed by (25%) had 2+ whereas (5%) had scanty sputum positivity while in HbA1c ≥6.5% maximum (47.50%) had 3+ followed by (40%) had 2+ whereas minimum (12.5%) had 1+ bacteriological grading. The association between sputum bacteriological level and HbA1c was statistically significant. (p=0.0001**)

Mean HbA1c amongst tuberculosis with diabetics was 10.24±1.2%, and 5.4±1.2% among tuberculosis without diabetes mellitus at pre-treatment. Similar findings can be found in previous studies Raghuraman S et al(2014)18.

In our study mean HbA1c amongst diabetics at the time of diagnosis was 10.24±1.2% and are significantly reduced to 7.05±0.58% after strict glycemic control with injectable insulin and/or oral hypoglycemic with ATT. At 2 months in patients with HbA1c ≥6.5%, (30%) cases had delayed sputum conversion whereas (6.25%) cases in HbA1c <6.5% had delayed conversion. Among patients with HbA1c ≥ 6.5% maximum delayed conversion among HbA1c 8-10%. At 3 months in patients with HbA1c ≥6.5%, (10%) cases had delayed sputum conversion whereas no cases in HbA1c <6.5% had delayed conversion.

Our study shows X-Ray lesion in lower lobes involvement with cavities in patients with DM (HbA1c ≥6.5%). This can be due to the fact that diabetes is an immune compromised state so the inflammatory reaction and events of TB do not follow the same guidelines as non-diabetics. Typical X ray findings of a tuberculosis patient varies in a diabetic. Usual finding of a consolidation can be less frequent in diabetic patient. Similar findings can be found in other studies19,20.

In our study we found that patients with diabetes mellitus have high bacterial grading denoting increased presence of bacteria in the circulation. This can be justified based on the fact that diabetes lowers the immunity of the patients and thus killing power of the body will not be as per to a non-diabetic patient. The study by R.Singla et al (2003)21 states that PTB-DM patients have an elevated pretreatment bacillary load, a lesser occurrence of drug resistance and delayed sputum conversion by the last of 2 months of management in comparison to non-diabetics. The link of DM does not change the ultimate management result amongst PTB patients. It understands the influence of the PTB patients.

In a study of medical and radiological outline of pulmonary tuberculosis among patients having diabetes mellitus by Mohapatra et al (2017) showed the presence of higher pre-treatment bacillary load. Also, chest x-ray images significantly depart from the typical presentation20.

In our study we found that patients with diabetes mellitus have high bacteriological grading. We demonstrated that HbA1c levels and bacillary loads were directly proportional to each other. Sputum smear conversion rate was delayed in TB patients with uncontrolled DM (HbA1c levels ≥6.5%) than controlled DM (HbA1c<6.5%) & without DM. This study highlights a need for more attention to control HbA1c levels in TB patients with DM to achieve a better outcome. However, treatment of tuberculosis remains same for both diabetics and non-diabetics according to NTEP guideline.

1. Kibirige, D. Endocrine dysfunction among adult patients with tuberculosis: An African experience. Indian Journal of Endocrinology and Metabolism, 2014; 18(3), 288-294.
2. Global tuberculosis report 2018. Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO.
3. Global tuberculosis report 2024. Geneva: World Health Organization; 2024. Licence: CC BY-NC-SA 3.0 IGO.
4. Viardot, A., Grey, S. T., Mackay, F., & Chisholm, D. Potential anti inflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype. Endocrinology, 2007;148(1), 346-353.
5. Stalenhoef, J. E., Alisjahbana, B., Nelwan, E. J., Van der Ven-Jongekrijg, J., Ottenhoff, T. H. M., Van Der Meer, J. W. M., ... & Van Crevel, R. The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus. European Journal of Clinical Microbiology & Infectious Diseases, 2008;27, 97-103.
6. TSUKAGUCHI, K., OKAMURA, H., IKUNO, M., KOBAYASHI, A., FUKUOKA, A., TAKENAKA, H., ... & NARITA, N. (1997). The relation between diabetes mellitus and IFN-γ , IL-12 and IL-10 productions BY CD 4+αβ at cells and monocytes IN patients with pulmonary tuberculosis. Kekkaku (Tuberculosis), 72(11), 617-622.
7. Delamaire, M., Maugendre, D., Moreno, M., Le Goff, M. C., Allannic, H., & Genetet, B. Impaired leucocyte functions in diabetic patients. Diabetic Medicine, 1997;14(1), 29-34.
8. Rayfield, E. J., Ault, M. J., Keusch, G. T., Brothers, M. J., Nechemias, C., & Smith, H. Infection and diabetes: the case for glucose control. The American journal of medicine, 1982;72(3), 439-450.
9. Jeon, C. Y., & Murray, M. B. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS medicine, 2008;5(7), e152.
10. Kumar, A., Gangwar, R., Ahmad Zargar, A., Kumar, R., & Sharma, A. Prevalence of diabetes in India: A review of IDF diabetes atlas 10th edition. Current diabetes reviews, 2024;20(1), 105-114.
11. Lee, R. E., Li, W., Chatterjee, D., & Lee, R. E. Rapid structural characterization of the arabinogalactan and lipoarabinomannan in live mycobacterial cells using 2D and 3D HR-MAS NMR: structural changes in the arabinan due to ethambutol treatment and gene mutation are observed. Glycobiology, 2005;15(2), 139-151.
12. Viswanathan, V., Bajaj, S., Kalra, S., Aggarwal, S., Atreja, A., Chaudhry, D.,... & Wilson, N. RSSDI clinical practice recommendations for diagnosis, prevention, and control of the diabetes mellitus-tuberculosis double burden. International Journal of Diabetes in Developing Countries, 2017;37, 379-399.
13. Van Cromphaut, S. J., Vanhorebeek, I., & d Berghe, G. V. (2008). Glucose metabolism and insulin resistance in sepsis. Current pharmaceutical design, 2008;14(19), 1887-1899.
14. Koenig, R. J., Peterson, C. M., Jones, R. L., Saudek, C., Lehrman, M., & Cerami, A. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. New England Journal of Medicine, 1976;295(8), 417420.
15. World Health Organization. (2004). Compendium of indicators for monitoring and evaluating national tuberculosis programs (No. WHO/HTM/TB/2004. 344). World Health Organization.
16. Tarbani I. Adam Malik Hospital Medan. Tesis. University of North Sumatera; 2007. Conversion of BTA Sputum in Intensive Phase Between Category I Pulmonary TB Conferencing Permanent Dosage and Generic Anti-Tuberculosis Medication in H.
17. Rasanathan, K., Sivasankara Kurup, A., Jaramillo, E., & Lönnroth, K. The social determinants of health: key to global tuberculosis control. The International Journal of Tuberculosis and Lung Disease, 2011;15(6), S30S36.
18. Raghuraman S, Vasudevan KP, Govindarajan S, Chinnakali P, Panigrahi KC. Prevalence of Diabetes Mellitus among Tuberculosis Patients in Urban Puducherry. N
19. Venkateswara Babu R, Manju R, Kumar SV, Das AK. A Comparative Study of Diabetes Mellitus in Pulmonary Tuberculosis Patients. World J Med Sci [Internet].2013 [cited 2018 Nov 1];9(2):93–6. Available from: https://pdfs.semanticscholar.org/b38d/40347b33c2b7484a0418c57409c1bd26b8cf.pdf
20. Mohapatra AK, Singh P, Subhankar S. Study of clinical and radiological profile of pulmonary tuberculosis among patients having diabetes mellitus. Int J Adv Med[Internet]. 2017 Sep 22;4(5):1378. Available from: http://www. ijmedicine.com/ index.php/ijam/article/view/725
21. Singla R, Khan N. Does diabetes predispose to the development of multi drug-resistant tuberculosis Chest. 2003;123(1):308–9.