Tuberculosis (TB) and Diabetes Mellitus (DM) have a significant bidirectional relationship, with DM tripling the risk of developing active TB compared to non-diabetic individuals1. This interaction poses a clinical challenge, as DM influences TB presentation and outcomes, while TB can complicate DM management2. 

Tuberculosis (TB), a widespread airborne infectious disease caused by *Mycobacterium tuberculosis*, affected 10.6 million people and caused 1.6 million deaths globally in 20213.The weakened immune system in diabetes patients, characterized by impaired cellular immunity, alveolar macrophage dysfunction, low interferon-gamma levels, lung microangiopathy, and micronutrient deficiencies, increases their risk of developing tuberculosis (TB). The complex interplay between TB and diabetes often leads to invasive and costly diagnostic investigations, emphasizing the need for better understanding, especially in the Indian context4-6.The radiographic appearance of TB is influenced by disease severity and the host’s immune status, with post-primary TB lesions commonly affecting the apical and posterior segments of the upper lobes and the superior segments of the lower lobes. Historically, Sosman and Steidl (1927) noted greater lower lung involvement in TB patients with diabetes (DM) compared to those without DM10. While DM profoundly impacts the clinical and radiological features of pulmonary TB, studies have shown conflicting evidence, with some reporting no significant differences in lower lung involvement between diabetic and non-diabetic patients7-10.In 2013, the International Diabetes Federation (IDF) reported 382 million individuals worldwide with diabetes, with 80% residing in low- and middle-income nations, and projected this number to rise to 592 million by 2035. Individuals with TB and diabetes face compromised immune responses, resulting in a higher risk of treatment failure, mortality, and disease recurrence, especially in multidrug-resistant TB (MDR-TB) cases. MDR-TB poses a significant global challenge due to treatment complexity, cost, and poor outcomes, particularly in individuals with diabetes, who have worse responses to therapy compared to non-diabetic MDR-TB patients. The prevalence of diabetes in drug-susceptible tuberculosis (DSTB) in India is 20%, whereas in multidrug-resistant tuberculosis (MDR TB) it is 11.7%. Presently, there is a scarcity of research on diabetic mellitus (DM) in tuberculosis (TB) patients, particularly in the specific geographical region being studied. Furthermore, there is a scarcity of research that accurately portray the clinical and radiological characteristics of diabetes mellitus in multidrugresistant tuberculosis.

AIM

This study aims to evaluate the clinical and radiological profiles of pulmonary TB and diabetes for improved diagnosis and management.

This comparative, observational study was conducted in the Department of Respiratory Medicine at Civil Hospital, Ganganagar, from OCT 2023 to NOV 2023, involving newly diagnosed, microbiologically confirmed drug-sensitive pulmonary TB patients aged above 15 years who voluntarily provided written consent. The diagnosis followed the guidelines of the National Tuberculosis Elimination Program (NTEP). Patients with drug-resistant pulmonary TB, those on immunosuppressant therapy, individuals with extrapulmonary TB or HIV, and those who did not consent to participate were excluded from the study.

The study divided patients into two groups: the control group included drug-sensitive pulmonary TB patients without diabetes mellitus (DM), while the case group comprised patients with either a prior or concurrent diagnosis of DM based on ADA guidelines. All participants provided written informed consent . Data collection involved a structured questionnaire covering demographics, clinical symptoms, comorbidities, lab investigations (including sputum AFB, HbA1c, and fasting glucose), and chest X-ray findings. Diagnoses of DM were confirmed for patients on hypoglycemic therapy or those meeting ADA criteria (fasting glucose ≥126 mg/dL or HbA1c ≥6.5%).

Table 1. Age Distribution of Pulmonary Tuberculosis

Table shows 60 tuberculosis (TB) cases, evenly distributed between those with diabetes mellitus (DM) and without, across age groups: 18–20 years (2 with DM, 5 without), 21–30 years (5 with DM, 9 without), 41–50 years (7 with DM, 6 without), 51–60 years (8 with DM, 3 without), and 61–70 years (8 with DM, 7 without).

TABLE 2: Difference in sputum AFB status at the time of diagnosis between cases vs. controls.

The sputum AFB smear analysis showed that among the 60 participants, negative results were seen in 12.5%, scant positivity in 7.5%, single positivity (+) in 25%, double positivity (++) in 32.5%, and triple positivity (+++) in 22.5%, with higher positivity levels (+/++/+++) observed in 90% of the case group and 70% of the control group (p-values ranging from 0.2308 to 1.0000).

TABLE 3: Lower zone involvement in chest X-ray among cases vs. controls.

The analysis of zone involvement showed that 85% of cases and 40% of controls had zones present, accounting for 61.7% of the total, while 15% of cases and 60% of controls had absent zones, making up 38.3% of the total across all 60 participants.

TABLE 4: Significance of chest X-ray cavitary lesions presentation between cases vs. controls.

The analysis of cavitary lesions revealed that 43% of cases and 10% of controls had lesions present, totaling 26.7%, while 57% of cases and 90% of controls had no lesions, comprising 73.3% of the 60 participants.

TABLE 5: Difference in hematological investigations in cases vs. controls.

Hematological tests showed no significant differences between cases and controls in TLC, platelet count, or RBC count, but HbA1c and fasting blood glucose levels were significantly higher in cases compared to controls (p < 0.0001).

Table 7: Radiological presentation of tuberculosis

Radiological findings showed higher rates of cavitary lesions (43% vs. 10%) and infiltrations (52% vs. 32%) in cases, similar consolidation rates (12% vs. 20%), and lung abscesses (8% vs. 0%) and bronchiectasis (4% vs. 2%) occurring predominantly in cases, reflecting distinct pulmonary patterns.

In the present study, the age group varied from 18 to 70 years of age and the highest number of TB with DM occurred in the 6th and 7th decade (51-70) of life (26%) and TB without DM occurred in the 3rd decade (21-30) of life (30%). TB with DM occurred after the 5th decade of life which is similar to the study conducted by Ullah H, et al. who reported 31% susceptibility between 41 to 50-year age group11. In another study conducted by Kouismi, et al. found that TB with diabetes mellitus prevailed more in the 6th decade of life12.

We found that two (10%) patients in the TB with DM group and three (15%) patients in the TB without DM group were negative for sputum AFB at the time of diagnosis. Although this result was not statistically significant in our study, it was similar to the results observed in other studies which reported a significantly higher frequency of negative sputum AFB in the TB without DM group13.

Our study reported that lower zone involvement in chest X-ray was significantly higher (Fisher’s exact test p-value = 0.0079) in pulmonary TB with DM (25/30, 85%) compared to pulmonary TB without DM group (12/30, 40%). Multiple previous studies showed the same atypical finding in chest X-rays 14-18.

In our study, we compared hematological parameters between the two groups (Table 3). Our data showed mean platelet count of 292.16±116.643 × 10³cells/mm³ in the case group and 290.05±77.454× 10³ cells/mm³ in the control group. The mean red blood cell count was 4.64±0.6802 × 10³ cells/mm³ in the case group, while in the control group, it was 4.26±0.5656 × 10³ cells/mm³. Our findings were overall consistent with a study that compared hematological findings between TB patients and healthy controls and reported that platelet count and granulocyte count were significantly higher and lymphocyte count and hemoglobin value were significantly lower in TB patients compared to the normal range19. However, we could not find any statistically significant difference between the TB with DM group and the TB without DM group in any of the above hematological parameters.

In the present study, the most common presentation in both groups is infiltrations, but infiltration is more common in patients with DM (52%) when compared with non-diabetic patients (32%). This is followed by cavitary lesions which are more in the diabetic group compared to the control group. The least common are pneumothorax in diabetic and bronchiectasis in the control group. The present study is similar to the study conducted by Mohapatra, et al. where the most common radiological presentation was infiltrations followed by cavitation and consolidation in both groups but is more in patients with DM compared to non-diabetic patients15.

In this study, we found that DM influences the clinical manifestations and radiological characteristics of pulmonary TB.  cavitary lesions, and lower zone involvement in chest X-rays were significantly predominant in TB with DM patients. Our study also reported differences in hematological parameters between the two groups. Based on our findings, we recommend screening all TB patients for DM, and, similarly, all high-risk DM patients should be screened for TB for early diagnosis and management, thereby reducing morbidity and mortality. Physicians should be aware that DM patients may present with pulmonary TB in an atypical manner.

1. Smith, Issar. "Mycobacterium Tuberculosis Pathogenesis and Molecular Determinants of Virulence." Clinical Microbiology Reviews, vol. 16, no. 3, 2003, pp. 463-96.
2. Dooley, Kelly E., and Richard E. Chaisson. "Tuberculosis and Diabetes Mellitus: Convergence of Two Epidemics." The Lancet Infectious Diseases, vol. 9, no. 12, 2009, pp. 737-46.
3. World Health Organization. Global Tuberculosis Report 2022. 2022, https://www.who.int/teams/globaltuberculosis-programme/tb-reports/global-tuberculosis-report-2022. Accessed 29 Aug. 2023.
4. Peleg, Anton Y., et al. "Common Infections in Diabetes: Pathogenesis, Management, and Relationship to Glycaemic Control." Diabetes/Metabolism Research and Reviews, vol. 23, no. 1, 2007, pp. 3-13.
5. Stegenga, Michiel E., et al. "Hyperglycemia Enhances Coagulation and Reduces Neutrophil Degranulation, Whereas Hyperinsulinemia Inhibits Fibrinolysis during Human Endotoxemia." Blood: The Journal of the American Society of Hematology, vol. 112, no. 1, 2008, pp. 82-89.
6. Webb, E. A., et al. "High Prevalence of Mycobacterium Tuberculosis Infection and Disease in Children and Adolescents with Type 1 Diabetes Mellitus." The International Journal of Tuberculosis and Lung Disease, vol. 13, no. 7, 2009, pp. 868-74.
7. Morris, J. T., Seaworth, B. J., and McAllister, C. K. "Pulmonary Tuberculosis in Diabetics." Chest, vol. 102, no. 2, 1992, pp. 539-41. https://doi.org/10.1378/chest.102.2.539.
8. Umut, S., Tosun, G. A., and Yildirim, N. "Radiographic Location of Pulmonary Tuberculosis in Diabetic Patients." Chest, vol. 106, no. 1, 1994, pp. 326. https://doi.org/10.1378/chest.106.1.326a.
9. al-Wabel, A. H., Teklu, B., Mahfouz, A. A., al-Ghamdi, A. S., el-Amin, O. B., and Khan, A. S. "Symptomatology and Chest Roentgenographic Changes of Pulmonary Tuberculosis among Diabetics." East African Medical Journal, vol. 74, 1997, pp. 62-64.
10. Baghaei, P., et al. "Comparison of Pulmonary TB Patients with and without Diabetes Mellitus Type II." Tanaffos, vol. 9, 2010, pp. 12-20.
11. Ullah, Hamid, et al. "Frequency of Pulmonary Tuberculosis in Patients Presenting with Diabetes." Pakistan Journal of Chest Medicine, vol. 15, no. 4, 2015, pp. [insert page range].
12. Kouismi, Hatim, et al. "Pulmonary Tuberculosis and Diabetes Mellitus Profile." Integrative Journal of Medical Sciences, vol. 2, no. 1, 2015, pp. 11-15.
13. Kuruva, P., Kandi, S. R., and Kandi, S. "Clinico-Radiological Profile and Treatment Outcome of Pulmonary Tuberculosis with and without Type 2 Diabetes Mellitus." Indian Journal of Tuberculosis, vol. 68, 2021, pp. 249-54. https://doi.org/10.1016/j.ijtb.2020.09.020.
14. Saxena, S., and Bhardwaj, G. "Study of Clinico-Radiological Profile of Pulmonary Tuberculosis in Diabetic and Nondiabetic Patients at Tertiary Care Hospital." European Journal of Molecular Clinical Medicine, vol. 9, 2022, pp. 9324-34.
15. Mohapatra, Amrut Kumar, Pratima Singh, and Saswat Subhankar. "Study of Clinical and Radiological Profile of Pulmonary Tuberculosis Among Patients Having Diabetes Mellitus." International Journal of Advances in Medicine, vol. 4, no. 5, 2017, pp. 1378-82.
16. Pérez-Guzmán, C., Torres-Cruz, A., Villarreal-Velarde, H., Salazar-Lezama, M. A., and Vargas, M. H. "Atypical Radiological Images of Pulmonary Tuberculosis in 192 Diabetic Patients: A Comparative Study." International Journal of Tuberculosis and Lung Disease, vol. 5, 2001, pp. 455-61.
17. Muhammed Faseed, C. H., Kumbar, A. S., and Harsha, D. S. "Pattern of Chest Radiographic Abnormalities and Comorbidities in Newly Detected Sputum Positive Pulmonary Tuberculosis Cases." IP Indian Journal of Immunology and Respiratory Medicine, vol. 6, 2021, pp. 10-17. https://doi.org/10.18231/j.ijirm.2021.003.
18. Shaikh, M. A., Singla, R., Khan, N. B., Sharif, N. S., and Saigh, M. O. "Does Diabetes Alter the Radiological Presentation of Pulmonary Tuberculosis?" Saudi Medical Journal, vol. 24, 2003, pp. 278-81.
19. Atomsa, D., Abebe, G., and Sewunet, T. "Immunological Markers and Hematological Parameters Among Newly Diagnosed Tuberculosis Patients at Jimma University Specialized Hospital." Ethiopian Journal of Health Sciences, vol. 24, 2014, pp. 311-18. https://doi.org/10.4314/ejhs.v24i4.6.