Tuberculosis, DM, and Socioeconomic Inequities

1. Disparities and Risk Factors in TB Diagnosis and Treatment

• Demographic disparities impact TB diagnosis and treatment: In Brunei, male contacts, household contacts, and exposure to smear-positive PTB cases increased LTBI risk. Foreign nationals and young children were less likely to initiate LTBI treatment. In US-born populations, Black individuals accounted for 38% of TB cases and 42% of TB-related deaths, with significant disparities persisting in marginalized racial and ethnic groups. Native Hawaiian/Other Pacific Islanders are projected to experience 75% disparity-associated TB cases by 2035.
• Socioeconomic factors contribute to TB risks: In Yogyakarta, low-income DM patients were at higher risk of developing pulmonary TB. In ASEAN, countries with lower health expenditure (e.g., Myanmar) had higher TB burdens. See also: Benang Merah Research Center
• Gender differences: Female DM patients in Yogyakarta had a 9.6 times higher risk of TB (borderline significance). In Brunei, female healthcare workers showed higher LTBI treatment acceptance, but in other settings, men exhibited delayed healthcare-seeking behavior and poorer adherence.

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2. TB and Comorbidities: Diabetes and Hyperglycemia

• Diabetes Mellitus (DM) significantly increases TB risk and worsens outcomes: Poor glycemic control (HbA1c > 7.0%) doubles the risk of TB. DM-TB patients exhibit higher HbA1c levels compared to DM-only patients.
• Hyperglycemia’s impact on TB: Long-term elevated glucose weakens immune responses, promoting TB progression. In China, age-standardized TB mortality related to hyperglycemia showed the greatest reduction in the 60-64 age group, identifying it as a key intervention period.
• Gender and metabolic factors: Men have higher TB mortality rates, potentially due to biological differences (e.g., estradiol enhances macrophage activation in women). Poor glucose control management is especially problematic in men due to behavioral factors like poor adherence.

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3. Treatment Challenges: Loss to Follow-Up and Completion Rates

• Treatment initiation and completion remain suboptimal: In Brunei, only 43% of LTBI cases initiated treatment, with 74% of those completing it. Progression to active TB occurred in 0.5% of LTBI cases, mostly within 8 years, even after treatment completion.
• Loss to Follow-Up (LTFU): Driven by low education, short-term migration, limited access to healthcare, low income, and unemployment. Behavioral factors such as alcohol use and smoking increase LTFU risk by impairing adherence.
• Migrants face compounded barriers: unstable housing, irregular employment, and lack of healthcare continuity lead to higher LTFU rates.
• Protective factors include health insurance and travel support, which ease financial and logistical barriers to treatment adherence. See also: Yoseph L. Samodra

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4. Regional Trends and Economic Burden of TB

• ASEAN regional trends (2002-2017): Six countries (Cambodia, Myanmar, Indonesia, Vietnam, Laos, Thailand) saw a steady decline in TB incidence. The Philippines reversed its initial decline post-2007, and Malaysia saw rising cases from 2009 onward. Singapore and Brunei had the lowest TB case numbers, correlating with their higher per capita health spending.
• US Projections (2023-2035): 26,203 TB cases and 3,264 deaths projected among US-born persons. Racial and ethnic disparities will drive 45% of TB cases and up to 66% of the projected $1.397 billion economic burden.
• Economic disparities and TB burden: Countries and populations with lower healthcare investment or access continue to experience higher TB rates and poorer outcomes. Addressing disparities is essential for reducing TB incidence and economic costs.

References:

1. Chaw, L., Hamid, R.A., Koh, K.S. and Thu, K., 2022. Contact investigation of tuberculosis in Brunei Darussalam: Evaluation and risk factor analysis. BMJ open respiratory research, 9(1).
2. Syafiq, N.J.M., Trivedi, A.A., Lai, A., Fontelera, M.P.A. and Lim, M.A., 2023. Latent tuberculosis infection in health-care workers in the government sector in Brunei Darussalam: A cross-sectional study. Journal of Integrative Nursing, 5(3), pp.197-202.
3. Swartwood, N.A., Li, Y., Regan, M., Marks, S.M., Barham, T., Asay, G.R.B., Cohen, T., Hill, A.N., Horsburgh, C.R., Khan, A.D. and McCree, D.H., 2024. Estimated Health and Economic Outcomes of Racial and Ethnic Tuberculosis Disparities in US-Born Persons. JAMA Network Open, 7(9), pp.e2431988-e2431988.
4. Nuraisyah, F., Juliana, N., Astaria, D., Khalisah, N., Al Fatih, D.M.F., Dewi, S.K. and Marwati, T., 2024. Risk Factors of Pulmonary Tuberculosis in Type 2 Diabetes Mellitus in Yogyakarta. Journal of Epidemiology and Public Health, 9(2), pp.194-203.
5. Shanmuham, V., Shetty, J.K. and Naik, V.R., 2022. Incidence of tuberculosis in the association of South-East Asia Nation (ASEAN) countries and its relation with health expenditure: a secondary data analysis. Manipal Journal of Nursing and Health Sciences, 8(1), p.7.
6. Rani, A.Y.A., Ismail, N., Zakaria, Y. and Isa, M.R., 2024. A scoping review on socioeconomic factors affecting tuberculosis loss to follow-up in Southeast Asia. Med J Malaysia, 79(4), pp.470-476.
7. Chen, Z., Liu, Q., Song, R., Zhang, W., Wang, T., Lian, Z., Sun, X. and Liu, Y., 2021. The association of glycemic level and prevalence of tuberculosis: a meta-analysis. BMC Endocrine Disorders, 21(1), p.123.
8. Wang C, Yang X, Zhang H, Zhang Y, Tao J, Jiang X and Wu C (2023) Temporal trends in mortality of tuberculosis attributable to high fasting plasma glucose in China from 1990 to 2019: a joinpoint regression and age-period-cohort analysis. Front. Public Health 11:1225931.

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Diabetes, Immune Response, and TB Susceptibility

· Diabetes Increases TB Risk

• DM is associated with a higher TB risk (HR: 1.90, OR: 1.61, RR: 1.60).
• Risk of TB recurrence is also elevated (HR: 1.35).
• The highest risk occurs within the first 10 years of DM diagnosis.
• Reducing diabetes burden is crucial for TB elimination. See also: Lin TB Lab

· Complexity of DM2-TB Relationship

• Factors like age, glucose control, and healthcare access affect TB risk in DM2 patients.
• Military personnel with DM2 have higher TB recurrence rates, but findings were not statistically significant.
• Contextual factors (e.g., healthcare resources, environmental exposure) play a major role. See also: Scholarships Info

· Immune Interactions in Prediabetes & TB

• Prediabetes alters immune responses, influencing TB susceptibility.
• Unique cytokine patterns (e.g., IL-27 ↑, IL-38 ↓, IL-17 ↑, IL-9 ↓) affect M. tb clearance.
• Insulin resistance-related inflammation may both protect against and worsen TB risk.
• Chronic diabetes further suppresses TB immunity, raising concerns about LTBI detection accuracy.

· Global & Regional TB Trends

• 30 high-burden countries account for 87% of TB cases, with India, Indonesia, and China leading.
• TB incidence in England is low (7.3/100,000), but disparities exist (foreign-born cases: 36.3/100,000).
• WHO’s ‘End TB’ strategy promotes new diagnostics and all-oral MDR/RR-TB regimens.

· Public-Private Mix (PPM) & TB Control in Pakistan

• PPM models improve TB detection & treatment success (90.6% success rate).
• NGOs perform best (94.9% success), while parastatal facilities perform worst (46.7%).
• Strengthening PPM can enhance TB control efforts.

· Diabetes & TB Comorbidity Debate

• Some studies unexpectedly found no statistical link between DM and TB.
• Rising DM prevalence, especially in low- and middle-income countries, poses a challenge to TB control.
• Integrated strategies are needed to tackle both diseases effectively.

References:

1. Franco, J.V., Bongaerts, B., Metzendorf, M.I., Risso, A., Guo, Y., Silva, L.P., Boeckmann, M., Schlesinger, S., Damen, J.A., Richter, B. and Baddeley, A., 2024. Diabetes as a risk factor for tuberculosis disease. The Cochrane database of systematic reviews, 8, p.CD016013.
2. Alvarado-Valdivia, N.T., Flores, J.A., Inolopú, J.L. and Rosales-Rimache, J.A., 2024. Type 2 diabetes mellitus and recurrent Tuberculosis: A retrospective cohort in Peruvian military workers. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 35, p.100432.
3. Aravindhan, V. and Yuvaraj, S., 2024. Immune-endocrine network in diabetes-tuberculosis nexus: does latent tuberculosis infection confer protection against meta-inflammation and insulin resistance?. Frontiers in Endocrinology, 15, p.1303338.
4. Ullah, W., Wali, A., Haq, M.U., Yaqoob, A., Fatima, R. and Khan, G.M., 2021. Public–private mix models of tuberculosis care in Pakistan: a high-burden country perspective. Frontiers in public health, 9, p.703631.
5. Khalid N, Ahmad F, Qureshi FM. Association amid the comorbidity of Diabetes Mellitus in patients of Active Tuberculosis in Pakistan: A matched case control study. Pak J Med Sci. 2021;37(3):816-820.
6. Meghji, J., Kon, O.M. and Ainley, A., 2023. Clinical tuberculosis. Medicine, 51(11), pp.768-773.

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Smoking, DM, and TB

• Smoking and TB Risk: Current smokers exhibit a higher TB incidence rate (0.60%) compared to never smokers (0.56%) and former smokers (0.59%). After adjusting for confounders, current smokers have a significantly higher TB risk (aHR 1.158), while former smokers show a reduced risk (aHR 0.947). TB risk increases with smoking intensity and duration. Smoking cessation is recommended to reduce TB risk, with emphasis on maintaining weight after quitting. Weight loss post-cessation increases TB risk. See also: Lin TB Lab
• Smoking and Active TB Risk: Current smoking doubles the risk of active TB compared to never smokers, with risk escalating based on cigarette consumption and years of smoking. Smoking contributes to 17% of TB cases in Taiwan, highlighting its significant role in TB incidence. The impact of smoking-related TB is more pronounced in individuals under 65 years. See also: Australia Scholarships
• Diabetes and TB in Indonesia: Indonesia has a high TB incidence and a growing diabetes prevalence, with studies showing strong connections between the two diseases. Routine diabetes screening for TB patients, especially those over 35, is recommended to improve management and treatment outcomes. Metformin use in TB-DM patients is linked to a higher treatment success rate and reduced all-cause mortality.
• Mtb Sensitization and Type 2 Diabetes: Mtb sensitization increases the risk of type 2 diabetes (T2DM), primarily through insulin resistance. Insulin resistance explained 18.3% of the Mtb-T2DM association, while β-cell dysfunction was not a significant factor.
• TB Screening in Diabetic Patients: Mass TB screening among persons with diabetes is feasible but not cost-efficient in low detection settings. Targeted screening in high TB incidence areas is more effective, with risk-stratified approaches recommended for lower-burden settings. Successful TB screening implementation requires integration with existing community-based diabetes screening efforts.
• Diabetes and TB Risk in Spain: Diabetic patients with TB are younger and have higher triglycerides, and are more frequently from Hindustan. TB incidence is higher among diabetic patients with elevated HbA1c levels, peaking at HbA1c ≥ 9%. No significant difference in TB localization, radiography, or skin test results based on HbA1c levels, but TB incidence increased with higher HbA1c.
• Diabetes and TB Disease Vulnerability: DM increases the risk of TB, with more severe DM increasing susceptibility. Effective TB elimination strategies should address both TB and DM management, especially in regions with high TB burdens and rising DM prevalence.

Recommendations:

• Smoking cessation and weight maintenance are crucial to reduce TB risk.
• Diabetic TB patients should be regularly screened and managed to improve treatment outcomes.
• Risk-based TB screening in diabetic populations, especially in high-burden areas, is recommended.

References:

1. Kim, S.H., Park, Y.M., Han, K., Ko, S.H., Kim, S.Y., Song, S.H., Kim, C.H., Hur, K.Y. and Kim, S.K., 2022. Association of weight change following smoking cessation with the risk of tuberculosis development: A nationwide population-based cohort study. Plos one, 17(4), p.e0266262.
2. Lin, H.H., Ezzati, M., Chang, H.Y. and Murray, M., 2009. Association between tobacco smoking and active tuberculosis in Taiwan: prospective cohort study. American journal of respiratory and critical care medicine, 180(5), pp.475-480.
3. Magodoro, I.M., Aluoch, A., Claggett, B., Nyirenda, M.J., Siedner, M.J., Wilkinson, K.A., Wilkinson, R.J. and Ntusi, N.A., 2024, October. Association Between Mycobacterium tuberculosis Sensitization and Insulin Resistance Among US Adults Screened for Type 2 Diabetes Mellitus. In Open Forum Infectious Diseases (Vol. 11, No. 10, p. ofae568). US: Oxford University Press.
4. Liu, Q., You, N., Wen, J., Wang, J., Ge, Y., Shen, Y., Ding, X., Lu, P., Chen, C., Zhu, B. and Zhu, L., 2023. Yield and efficiency of a population-based mass tuberculosis screening intervention among persons with diabetes in Jiangsu Province, China. Clinical Infectious Diseases, 77(1), pp.103-111.
5. Alisjahbana, B., Sahiratmadja, E., Nelwan, E.J., Purwa, A.M., Ahmad, Y., Ottenhoff, T.H., Nelwan, R.H., Parwati, I., Meer, J.W.V.D. and Crevel, R.V., 2007. The effect of type 2 diabetes mellitus on the presentation and treatment response of pulmonary tuberculosis. Clinical infectious diseases, 45(4), pp.428-435.
6. Chung, E., Jeong, D., Mok, J., Jeon, D., Kang, H.Y., Kim, H., Kim, H., Choi, H. and Kang, Y.A., 2024. Relationship between metformin use and mortality in tuberculosis patients with diabetes: a nationwide cohort study. The Korean Journal of Internal Medicine, 39(2), p.306.
7. Antonio-Arques, V., Caylà, J.A., Real, J., Moreno-Martinez, A., Orcau, À., Mauricio, D., Mata-Cases, M., Julve, J., Navas Mendez, E., Puig Treserra, R. and Millet, J.P., 2022. Glycemic control and the risk of tuberculosis in patients with diabetes: A cohort study in a Mediterranean city. Frontiers in public health, 10, p.1017024.
8. Baker, M.A., Lin, H.H., Chang, H.Y. and Murray, M.B., 2012. The risk of tuberculosis disease among persons with diabetes mellitus: a prospective cohort study. Clinical Infectious Diseases, 54(6), pp.818-825.

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