Exploring the Protective Role of Obesity and the Therapeutic Potential of Metformin

BMI and Drug-Resistant Tuberculosis (DR-TB)

• Higher BMI (overweight/obese) is associated with increased rates of DR-TB and MDR-TB, with obese patients showing the highest proportion of MDR-TB (17.39%).
• Underweight individuals are more prone to isoniazid (INH) resistance, highlighting BMI-specific vulnerabilities.
• Being overweight increases the likelihood of MDR-TB (adjusted OR ~1.54), although the statistical significance is borderline.
• Males and individuals with comorbidities are important risk factors for DR-TB across different BMI categories.
• Study insights support tailoring TB control strategies to specific BMI-related risk factors. See also: Yoseph Samodra

Obesity and TB Risk: The Paradox

• Obesity is paradoxically protective against TB, with obese individuals showing a ~67–72% reduction in TB risk compared to normal-weight peers.
• Despite the higher prevalence of diabetes in obese individuals (a known TB risk factor), the protective effect of high BMI outweighs the risk posed by diabetes.
• Underweight individuals with DM face the highest TB risk, while severely obese individuals have the lowest TB incidence, reinforcing BMI's protective role.

Metformin’s Role in TB Management

• Metformin reduces the risk of active TB in diabetic patients, potentially by boosting immune responses.
• Metformin use improves TB treatment outcomes, including higher treatment success rates (90.3% vs. 87.6%) and lower all-cause mortality (9.5% vs. 12.4%).
• Consistent protective effects of metformin across gender groups, with reduced mortality confirmed in propensity score–matched cohorts.
• Metformin may serve as a host-directed therapy (HDT) for TB-DM patients, enhancing immune defense without directly targeting the bacteria.

TB, Diabetes, and Metabolic Implications

• TB infection can induce hyperglycemia and insulin resistance, which increases the risk of developing type 2 diabetes mellitus (T2DM) later in life.
• Successful TB treatment can normalize blood glucose levels, but long-term metabolic risks remain.
• TB disrupts lipid metabolism, contributing to insulin resistance and abnormal lipid profiles (elevated LDL, reduced HDL, increased VLDL).
• Co-occurrence of TB and DM worsens TB outcomes, increasing MDR-TB risk and complicating treatment due to impaired immune responses in diabetic individuals.

Glycemic Control During TB Treatment (India Study)

• Significant A1C reductions observed during intensive TB treatment, especially in newly diagnosed DM cases.
• No progression to DM in normoglycemic or pre-DM individuals, with most pre-DM participants reverting to normoglycemia post-treatment.
• Some known-DM participants showed improved glycemic status, reverting to pre-DM or normoglycemia by the end of follow-up.
• Better A1C trends linked to successful TB cure, despite inconsistent long-term glycemic benefits from antidiabetic treatments.

Public Health Implications

• Integrated strategies addressing both malnutrition and metabolic diseases are essential to reducing TB burden.
• BMI management is as crucial as diabetes control for TB prevention and treatment.
• Host-directed therapies like metformin offer promising adjunctive treatment options for TB-DM comorbidity.

References:

1. Song, W.M., Guo, J., Xu, T.T., Li, S.J., Liu, J.Y., Tao, N.N., Liu, Y., Zhang, Q.Y., Liu, S.Q., An, Q.Q. and Li, Y.F., 2021. Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019. BMC pulmonary medicine, 21, pp.1-14.
2. Lin, H.H., Wu, C.Y., Wang, C.H., Fu, H., Lönnroth, K., Chang, Y.C. and Huang, Y.T., 2018. Association of obesity, diabetes, and risk of tuberculosis: two population-based cohorts. Clinical Infectious Diseases, 66(5), pp.699-705.
3. Choi, H., Yoo, J.E., Han, K., Choi, W., Rhee, S.Y., Lee, H. and Shin, D.W., 2021. Body mass index, diabetes, and risk of tuberculosis: a retrospective cohort study. Frontiers in nutrition, 8, p.739766.
4. 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.
5. Yu, X., Li, L., Xia, L., Feng, X., Chen, F., Cao, S. and Wei, X., 2019. Impact of metformin on the risk and treatment outcomes of tuberculosis in diabetics: a systematic review. BMC infectious diseases, 19, pp.1-11.
6. Bisht MK, Dahiya P, Ghosh S and Mukhopadhyay S (2023) The cause-effect relation of tuberculosis on incidence of diabetes mellitus. Front. Cell. Infect. Microbiol. 13:1134036.
7. Kornfeld, H., Procter-Gray, E., Kumpatla, S., Kane, K., Li, W., Magee, M.J., Babu, S. and Viswanathan, V., 2023. Longitudinal trends in glycated hemoglobin during and after tuberculosis treatment. Diabetes Research and Clinical Practice, 196, p.110242.

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