Skip to main content
SpringerLink
Log in

Diabetes and Tuberculosis

  • Chapter
  • First Online:
Understanding the Host Immune Response Against Mycobacterium tuberculosis Infection

Abstract

The worldwide increase in the prevalence of diabetes has been most notable in TB-endemic countries and has led to the re-emerging importance of the association between these two diseases. Today, type 2 diabetes is one of the most prevalent comorbidities and risk factors in TB patients, along with undernutrition and HIV/AIDS. However, it is striking how little we know about the underlying biology of the association between TB and diabetes. In this chapter, I first provide an overview of the epidemiology and characteristic clinical findings associated with patients who have both diseases. Then I review the current knowledge on underlying biology on the association. Essentially, studies in animal models of diabetes and TB and ex vivo studies with immune cells from patients with diabetes suggest a model where the initial Mycobacterium tuberculosis infection in the diabetic host is characterized by a delayed and underperforming response by monocytes and macrophages. These defects provide a critical early opportunity for favorable replication of M. tuberculosis within the diabetic alveolar macrophages. Eventual but delayed T-cell priming does occur, and in TB patients, this T-cell response is exaggerated, perhaps as a reflection of higher M. tuberculosis burden in TB with diabetes (vs. TB with no diabetes). The metabolic alterations characteristic of diabetes (e.g., chronic hyperglycemia, metabolic inflammation [meta-inflammation], oxidative stress) are likely to contribute to the immune dysfunction to mycobacteria. The discovery of these mechanisms is providing the knowledge base to design host-directed therapies for TB patients with diabetes, and perhaps those without diabetes as well.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdelbary, B. E., Garcia-Viveros, M., Ramirez-Oropesa, H., Rahbar, M. H., & Restrepo, B. I. (2016). Tuberculosis-diabetes epidemiology in the border and non-border regions of Tamaulipas, Mexico. Tuberculosis (Edinburgh, Scotland), 101S, S124–S134.

    Article  Google Scholar 

  • Abdelbary, B. E., Garcia-Viveros, M., Ramirez-Oropesa, H., Rahbar, M. H., & Restrepo, B. I. (2017). Predicting treatment failure, death and drug resistance using a computed risk score among newly diagnosed TB patients in Tamaulipas, Mexico. Epidemiology and Infection, 145, 3020–3034.

    Article  CAS  PubMed  Google Scholar 

  • Al-Rifai, R. H., Pearson, F., Critchley, J. A., & Abu-Raddad, L. J. (2017). Association between diabetes mellitus and active tuberculosis: A systematic review and meta-analysis. PLoS One, 12, e0187967.

    Article  PubMed  PubMed Central  Google Scholar 

  • American-Diabetes-Association. (2014). Standards of medical care in diabetes--2014. Diabetes Care, 37(Suppl 1), S14–S80.

    Article  Google Scholar 

  • Andrade, B. B., Pavan, K. N., Sridhar, R., Banurekha, V. V., Jawahar, M. S., Nutman, T. B., Sher, A., & Babu, S. (2014). Heightened plasma levels of heme oxygenase-1 and tissue inhibitor of metalloproteinase-4 as well as elevated peripheral neutrophil counts are associated with TB-diabetes comorbidity. Chest, 145, 1244–1254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker, M. A., Harries, A. D., Jeon, C. Y., Hart, J. E., Kapur, A., Lonnroth, K., Ottmani, S. E., Goonesekera, S. D., & Murray, M. B. (2011). The impact of diabetes on tuberculosis treatment outcomes: A systematic review. BMC Medicine, 9, 81.

    Article  PubMed  PubMed Central  Google Scholar 

  • Baker, M. A., Lin, H. H., Chang, H. Y., & Murray, M. B. (2012). The risk of tuberculosis disease among persons with diabetes mellitus: A prospective cohort study. Clinical Infectious Diseases, 54, 818–825.

    Article  PubMed  Google Scholar 

  • Bashar, M., Alcabes, P., Rom, W. N., & Condos, R. (2001). Increased incidence of multidrug-resistant tuberculosis in diabetic patients on the Bellevue Chest Service, 1987 to 1997. Chest, 120, 1514–1519.

    Article  CAS  PubMed  Google Scholar 

  • Behr, M. A., Warren, S. A., Salamon, H., Hopewell, P. C., Ponce de, L. A., Daley, C. L., & Small, P. M. (1999). Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet, 353, 444–449.

    Article  CAS  PubMed  Google Scholar 

  • Boillat-Blanco, N., Ramaiya, K. L., Mganga, M., Minja, L. T., Bovet, P., Schindler, C., Von Eckardstein, A., Gagneux, S., Daubenberger, C., Reither, K., et al. (2016). Transient hyperglycemia in patients with tuberculosis in Tanzania: Implications for diabetes screening algorithms. The Journal of Infectious Diseases, 213, 1163–1172.

    Article  CAS  PubMed  Google Scholar 

  • Boucot, K. R., Dillon, E. S., Cooper, D. A., Meier, P., & Richardson, R. (1952). Tuberculosis among diabetics: The Philadelphia survey. American Review of Tuberculosis, 65, 1–50.

    CAS  PubMed  Google Scholar 

  • Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813–820.

    Article  CAS  PubMed  Google Scholar 

  • Cheekatla, S. S., Tripathi, D., Venkatasubramanian, S., Nathella, P. K., Paidipally, P., Ishibashi, M., Welch, E., Tvinnereim, A. R., Ikebe, M., Valluri, V. L., et al. (2016). NK-CD11c+ cell crosstalk in diabetes enhances IL-6-mediated inflammation during Mycobacterium tuberculosis infection. PLoS Pathogens, 12, e1005972.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dalmas, E., & Donath, M. Y. (2014). A role for interleukin-22 in the alleviation of metabolic syndrome. Nature Medicine, 20, 1379–1381.

    Article  CAS  PubMed  Google Scholar 

  • Delgado-Sanchez, G., Garcia-Garcia, L., Castellanos-Joya, M., Cruz-Hervert, P., Ferreyra-Reyes, L., Ferreira-Guerrero, E., Hernandez, A., Ortega-Baeza, V. M., Montero-Campos, R., Sulca, J. A., et al. (2015). Association of pulmonary tuberculosis and diabetes in Mexico: Analysis of the national tuberculosis registry 2000-2012. PLoS One, 10, e0129312.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Faurholt-Jepsen, D., Aabye, M. G., Jensen, A. V., Range, N., PrayGod, G., Jeremiah, K., Changalucha, J., Faurholt-Jepsen, M., Jensen, L., Jensen, S. M., et al. (2014). Diabetes is associated with lower tuberculosis antigen-specific interferon gamma release in Tanzanian tuberculosis patients and non-tuberculosis controls. Scandinavian Journal of Infectious Diseases, 46, 384–391.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Real, J. M., & Pickup, J. C. (2012). Innate immunity, insulin resistance and type 2 diabetes. Diabetologia, 55, 273–278.

    Article  CAS  PubMed  Google Scholar 

  • Fisher-Hoch, S. P., Whitney, E., McCormick, J. B., Crespo, G., Smith, B., Rahbar, M. H., & Restrepo, B. I. (2008). Type 2 diabetes and multidrug-resistant tuberculosis. Scandinavian Journal of Infectious Diseases, 40, 888–893.

    Article  PubMed  PubMed Central  Google Scholar 

  • Getahun, H., Gunneberg, C., Granich, R., & Nunn, P. (2010). HIV infection-associated tuberculosis: The epidemiology and the response. Clinical Infectious Diseases, 50(Suppl 3), S201–S207.

    Article  PubMed  Google Scholar 

  • Giacco, F., & Brownlee, M. (2010). Oxidative stress and diabetic complications. Circulation Research, 107, 1058–1070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goetze, A. M., Liu, Y. D., Arroll, T., Chu, L., & Flynn, G. C. (2012). Rates and impact of human antibody glycation in vivo. Glycobiology, 22, 221–234.

    Article  CAS  PubMed  Google Scholar 

  • Goldhaber-Fiebert, J. D., Jeon, C. Y., Cohen, T., & Murray, M. B. (2011). Diabetes mellitus and tuberculosis in countries with high tuberculosis burdens: Individual risks and social determinants. International Journal of Epidemiology, 40, 417–428.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gomez, D. I., Twahirwa, M., Schlesinger, L. S., & Restrepo, B. I. (2013). Reduced Mycobacterium tuberculosis association with monocytes from diabetes patients that have poor glucose control. Tuberculosis, 93, 192–197.

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Gomez, A., Magana-Aquino, M., Lopez-Meza, S., Aranda-Alvarez, M., Diaz-Ornelas, D. E., Hernandez-Segura, M. G., Salazar-Lezama, M. A., Castellanos-Joya, M., & Noyola, D. E. (2015). Diabetes and other risk factors for multi-drug resistant tuberculosis in a Mexican population with pulmonary tuberculosis: Case control study. Archives of Medical Research, 46, 142–148.

    Article  PubMed  Google Scholar 

  • Gonzalez-Curiel, I., Castaneda-Delgado, J., Lopez-Lopez, N., Araujo, Z., Hernandez-Pando, R., Gandara-Jasso, B., ias-Segura, N., Enciso-Moreno, A., & Rivas-Santiago, B. (2011). Differential expression of antimicrobial peptides in active and latent tuberculosis and its relationship with diabetes mellitus. Human Immunology, 72, 656–662.

    Article  CAS  PubMed  Google Scholar 

  • Guirado, E., Schlesinger, L. S., & Kaplan, G. (2013). Macrophages in tuberculosis: Friend or foe. Seminars in Immunopathology, 35, 563–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris, J., & Keane, J. (2010). How tumour necrosis factor blockers interfere with tuberculosis immunity. Clinical and Experimental Immunology, 161, 1–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hasnain, S. Z., Borg, D. J., Harcourt, B. E., Tong, H., Sheng, Y. H., Ng, C. P., Das, I., Wang, R., Chen, A. C., Loudovaris, T., et al. (2014). Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress. Nature Medicine, 20, 1417–1426.

    Article  CAS  PubMed  Google Scholar 

  • Herrera, M. T., Gonzalez, Y., Hernandez-Sanchez, F., Fabian-San Miguel, G., & Torres, M. (2017). Low serum vitamin D levels in type 2 diabetes patients are associated with decreased mycobacterial activity. BMC Infectious Diseases, 17, 610.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hsu, A. H., Lee, J. J., Chiang, C. Y., Li, Y. H., Chen, L. K., & Lin, C. B. (2013). Diabetes is associated with drug- resistant tuberculosis in Eastern Taiwan. The International Journal of Tuberculosis and Lung Disease, 17, 354–356.

    Article  PubMed  Google Scholar 

  • Hu, F. (2011). Globalization of diabetes: The role of diet, lifestyle, and genes. Diabetes Care, 34, 1249–1257.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huangfu, P., Pearson, F., Ugarte-Gil, C., & Critchley, J. (2017). Diabetes and poor tuberculosis treatment outcomes: Issues and implications in data interpretation and analysis. The International Journal of Tuberculosis and Lung Disease, 21, 1214–1219.

    Article  CAS  PubMed  Google Scholar 

  • International-Diabetes-Federation. (2015). IDF diabetes atlas (7th ed.). Brussels, Belgium: International Diabetes Federation.

    Google Scholar 

  • Islamoglu, H., Cao, R., Teskey, G., Gyurjian, K., Lucar, S., Fraix, M. P., Sathananthan, A., Chan, J. K., & Venketaraman, V. (2018). Effects of ReadiSorb L-GSH in altering granulomatous responses against Mycobacterium tuberculosis infection. Journal of Clinical Medicine, 7, pii: E40.

    Article  Google Scholar 

  • Jeon, C. Y., & Murray, M. B. (2008). Diabetes mellitus increases the risk of active tuberculosis: A systematic review of 13 observational studies. PLoS Medicine, 5, 1091–1101.

    Google Scholar 

  • Jeon, C. Y., Murray, M. B., & Baker, M. A. (2012). Managing tuberculosis in patients with diabetes mellitus: Why we care and what we know. Expert Review of Anti-Infective Therapy, 10, 863–868.

    Article  CAS  PubMed  Google Scholar 

  • Jimenez-Corona, M. E., Cruz-Hervert, L. P., Garcia-Garcia, L., Ferreyra-Reyes, L., Delgado-Sanchez, G., Bobadilla-del-Valle, M., Canizales-Quintero, S., Ferreira-Guerrero, E., Baez-Saldana, R., Tellez-Vazquez, N., et al. (2013). Association of diabetes and tuberculosis: Impact on treatment and post-treatment outcomes. Thorax, 68, 214–220.

    Article  PubMed  Google Scholar 

  • Jorgensen, M. E., & Faurholt-Jepsen, D. (2014). Is there an effect of glucose lowering treatment on incidence and prognosis of tuberculosis? A systematic review. Current Diabetes Reports, 14, 505.

    Article  PubMed  CAS  Google Scholar 

  • Kornfeld, H., West, K., Kane, K., Kumpatla, S., Zacharias, R. R., Martinez-Balzano, C., Li, W., & Viswanathan, V. (2016). High prevalence and heterogeneity of diabetes in patients with TB in South India: A report from the effects of diabetes on tuberculosis severity (EDOTS) study. Chest, 149, 1501–1508.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kumar, N. P., Sridhar, R., Banurekha, V. V., Jawahar, M. S., Fay, M. P., Nutman, T. B., & Babu, S. (2013a). Type 2 diabetes mellitus coincident with pulmonary tuberculosis is associated with heightened systemic type 1, type 17, and other proinflammatory cytokines. Annals of the American Thoracic Society, 10, 441–449.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kumar, N. P., Sridhar, R., Banurekha, V. V., Jawahar, M. S., Nutman, T. B., & Babu, S. (2013b). Expansion of pathogen-specific T-helper 1 and T-helper 17 cells in pulmonary tuberculosis with coincident type 2 diabetes mellitus. The Journal of Infectious Diseases, 208, 739–748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar, N. P., George, P. J., Kumaran, P., Dolla, C. K., Nutman, T. B., & Babu, S. (2014). Diminished systemic and antigen-specific type 1, type 17, and other proinflammatory cytokines in diabetic and prediabetic individuals with latent Mycobacterium tuberculosis infection. The Journal of Infectious Diseases, 210, 1670–1678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar, N. P., Banurekha, V. V., Nair, D., Kumaran, P., Dolla, C. K., & Babu, S. (2015a). Type 2 diabetes – tuberculosis co-morbidity is associated with diminished circulating levels of IL-20 subfamily of cytokines. Tuberculosis (Edinburgh, Scotland), 95, 707–712.

    Article  CAS  Google Scholar 

  • Kumar, N. P., Sridhar, R., Nair, D., Banurekha, V. V., Nutman, T. B., & Babu, S. (2015b). Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis. Immunology, 144, 677–686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar, N. P., Moideen, K., George, P. J., Dolla, C., Kumaran, P., & Babu, S. (2016a). Coincident diabetes mellitus modulates Th1-, Th2-, and Th17-cell responses in latent tuberculosis in an IL-10- and TGF-beta- dependent manner. European Journal of Immunology, 46, 390–399.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, N. P., Moideen, K., George, P. J., Dolla, C., Kumaran, P., & Babu, S. (2016b). Impaired cytokine but enhanced cytotoxic marker expression in Mycobacterium tuberculosis-induced CD8+ T cells in individuals with type 2 diabetes and latent Mycobacterium tuberculosis infection. The Journal of Infectious Diseases, 213, 866–870.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, N. P., Moideen, K., Sivakumar, S., Menon, P. A., Viswanathan, V., Kornfeld, H., & Babu, S. (2017a). Tuberculosis-diabetes co-morbidity is characterized by heightened systemic levels of circulating angiogenic factors. The Journal of Infection, 74, 10–21.

    Article  PubMed  Google Scholar 

  • Kumar, N. P., Moideen, K., Viswanathan, V., Sivakumar, S., Menon, P. A., Kornfeld, H., & Babu, S. (2017b). Heightened circulating levels of antimicrobial peptides in tuberculosis-diabetes co-morbidity and reversal upon treatment. PLoS One, 12, e0184753.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kuo, M. C., Lin, S. H., Lin, C. H., Mao, I. C., Chang, S. J., & Hsieh, M. C. (2013). Type 2 diabetes: An independent risk factor for tuberculosis: A nationwide population-based study. PLoS One, 8, e78924.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lagman, M., Ly, J., Saing, T., Kaur Singh, M., Vera Tudela, E., Morris, D., Chi, P. T., Ochoa, C., Sathananthan, A., & Venketaraman, V. (2015). Investigating the causes for decreased levels of glutathione in individuals with type II diabetes. PLoS One, 10, e0118436.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lai, C. C., Lee, M. T., Lee, S. H., Hsu, W. T., Chang, S. S., Chen, S. C., & Lee, C. C. (2016). Statin treatment is associated with a decreased risk of active tuberculosis: An analysis of a nationally representative cohort. Thorax, 71, 646–651.

    Article  PubMed  Google Scholar 

  • Leeds, I. L., Magee, M. J., Kurbatova, E. V., del, R. C., Blumberg, H. M., Leonard, M. K., & Kraft, C. S. (2012). Site of extrapulmonary tuberculosis is associated with HIV infection. Clinical Infectious Diseases, 55, 75–81.

    Article  PubMed  PubMed Central  Google Scholar 

  • Leung, C. C., Lam, T. H., Chan, W. M., Yew, W. W., Ho, K. S., Leung, G. M., Law, W. S., Tam, C. M., Chan, C. K., & Chang, K. C. (2008). Diabetic control and risk of tuberculosis: A cohort study. American Journal of Epidemiology, 167, 1486–1494.

    Article  PubMed  Google Scholar 

  • Lonnroth, K., Jaramillo, E., Williams, B. G., Dye, C., & Raviglione, M. (2009). Drivers of tuberculosis epidemics: The role of risk factors and social determinants. Social Science & Medicine, 68, 2240–2246.

    Article  Google Scholar 

  • Lonnroth, K., Roglic, G., & Harries, A. D. (2014). Improving tuberculosis prevention and care through addressing the global diabetes epidemic: From evidence to policy and practice. The Lancet Diabetes and Endocrinology, 2, 730–739.

    Article  PubMed  Google Scholar 

  • Lopez-Lopez, N., Martinez, A. G. R., Garcia-Hernandez, M. H., Hernandez-Pando, R., Castaneda-Delgado, J. E., Lugo-Villarino, G., Cougoule, C., Neyrolles, O., Rivas-Santiago, B., Valtierra-Alvarado, M. A., et al. (2018). Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis. Memórias do Instituto Oswaldo Cruz, 113, e170326.

    Article  PubMed  PubMed Central  Google Scholar 

  • Magee, M. J., Bloss, E., Shin, S. S., Contreras, C., Huaman, H. A., Ticona, J. C., Bayona, J., Bonilla, C., Yagui, M., Jave, O., et al. (2013). Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru. International Journal of Infectious Diseases, 17, e404–e412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magee, M. J., Kempker, R. R., Kipiani, M., Gandhi, N. R., Darchia, L., Tukvadze, N., Howards, P. P., Narayan, K. M., & Blumberg, H. M. (2015). Diabetes mellitus is associated with cavities, smear grade, and multidrug- resistant tuberculosis in Georgia. The International Journal of Tuberculosis and Lung Disease, 19, 685–692.

    Article  CAS  PubMed  Google Scholar 

  • Martens, G. W., Arikan, M. C., Lee, J., Ren, F., Greiner, D., & Kornfeld, H. (2007). Tuberculosis susceptibility of diabetic mice. American Journal of Respiratory Cell and Molecular Biology, 37, 518–524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez, N., & Kornfeld, H. (2014). Diabetes and immunity to tuberculosis. European Journal of Immunology, 44, 617–626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez, N., Ketheesan, N., West, K., Vallerskog, T., & Kornfeld, H. (2016). Impaired recognition of Mycobacterium tuberculosis by alveolar macrophages from diabetic mice. The Journal of Infectious Diseases, 214, 1629–1637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morton, R. (1694). Phthisiologia, or A treatise of consumptions. London, UK.

    Google Scholar 

  • Muller, L. M., Gorter, K. J., Hak, E., Goudzwaard, W. L., Schellevis, F. G., Hoepelman, A. I., & Rutten, G. E. (2005). Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. Clinical Infectious Diseases, 41, 281–288.

    Article  CAS  PubMed  Google Scholar 

  • Odone, A., Houben, R. M., White, R. G., & Lonnroth, K. (2014). The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets. The Lancet Diabetes and Endocrinology, 2, 754–764.

    Article  PubMed  Google Scholar 

  • Ottmani, S. E., Murray, M. B., Jeon, C. Y., Baker, M. A., Kapur, A., Lonnroth, K., & Harries, A. D. (2010). Consultation meeting on tuberculosis and diabetes mellitus: Meeting summary and recommendations. The International Journal of Tuberculosis and Lung Disease, 14, 1513–1517.

    PubMed  Google Scholar 

  • Pan, S. C., Ku, C. C., Kao, D., Ezzati, M., Fang, C. T., & Lin, H. H. (2015). Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: A modelling study. The Lancet Diabetes and Endocrinology, 3, 323–330.

    Article  PubMed  Google Scholar 

  • Parihar, S. P., Guler, R., Khutlang, R., Lang, D. M., Hurdayal, R., Mhlanga, M. M., Suzuki, H., Marais, A. D., & Brombacher, F. (2014). Statin therapy reduces the mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation. The Journal of Infectious Diseases, 209, 754–763.

    Article  CAS  PubMed  Google Scholar 

  • Perez-Navarro, L. M., Fuentes-Dominguez, F. J., & Zenteno-Cuevas, R. (2015). Type 2 diabetes mellitus and its influence in the development of multidrug resistance tuberculosis in patients from southeastern Mexico. Journal of Diabetes and its Complications, 29, 77–82.

    Article  PubMed  Google Scholar 

  • Perez-Navarro, L. M., Restrepo, B. I., Fuentes-Dominguez, F. J., Duggirala, R., Morales-Romero, J., Lopez-Alvarenga, J. C., Comas, I., & Zenteno-Cuevas, R. (2017). The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes. Tuberculosis (Edinburgh, Scotland), 103, 83–91.

    Article  CAS  Google Scholar 

  • Pickup, J. C. (2004). Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care, 27, 813–823.

    Article  PubMed  Google Scholar 

  • Podell, B. K., Ackart, D. F., Obregon-Henao, A., Eck, S. P., Henao-Tamayo, M., Richardson, M., Orme, I. M., Ordway, D. J., & Basaraba, R. J. (2014). Increased severity of tuberculosis in Guinea pigs with type 2 diabetes: a model of diabetes-tuberculosis comorbidity. American Journal of Pathology, 184, 1104–1118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ponce-De-Leon, A., Garcia-Garcia, M. D. L., Garcia-Sancho, M. C., Gomez-Perez, F. J., Valdespino-Gomez, J. L., Olaiz-Fernandez, G., Rojas, R., Ferreyra-Reyes, L., Cano-Arellano, B., Bobadilla, M., et al. (2004). Tuberculosis and diabetes in southern Mexico. Diabetes Care, 27, 1584–1590.

    Article  PubMed  Google Scholar 

  • Prada-Medina, C. A., Fukutani, K. F., Pavan Kumar, N., Gil-Santana, L., Babu, S., Lichtenstein, F., West, K., Sivakumar, S., Menon, P. A., Viswanathan, V., et al. (2017). Systems immunology of diabetes-tuberculosis comorbidity reveals signatures of disease complications. Scientific Reports, 7, 1999.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Reed, G. W., Choi, H., Lee, S. Y., Lee, M., Kim, Y., Park, H., Lee, J., Zhan, X., Kang, H., Hwang, S., et al. (2013). Impact of diabetes and smoking on mortality in tuberculosis. PLoS One, 8, e58044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reis-Santos, B., Locatelli, R., Horta, B. L., Faerstein, E., Sanchez, M. N., Riley, L. W., & Maciel, E. L. (2013). Socio-demographic and clinical differences in subjects with tuberculosis with and without diabetes mellitus in Brazil – a multivariate analysis. PLoS One, 8, e62604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Restrepo, B. I. (2007). Convergence of the tuberculosis and diabetes epidemics: Renewal of old acquaintances. Clinical Infectious Diseases, 45, 436–438.

    Article  PubMed  Google Scholar 

  • Restrepo, B. I. (2016). Metformin: Candidate host-directed therapy for tuberculosis in diabetes and non-diabetes patients. Tuberculosis, 101, S69–S72.

    Article  CAS  Google Scholar 

  • Restrepo, B. I., & Schlesinger, L. S. (2014). Impact of diabetes on the natural history of tuberculosis. Diabetes Research and Clinical Practice, 106, 191–199.

    Article  PubMed  PubMed Central  Google Scholar 

  • Restrepo, B. I., Fisher-Hoch, S. P., Crespo, J. G., Whitney, E., Perez, A., Smith, B., & McCormick, J. B. (2007). Type 2 diabetes and tuberculosis in a dynamic bi-national border population. Epidemiology and Infection, 135, 483–491.

    Article  CAS  PubMed  Google Scholar 

  • Restrepo, B. I., Fisher-Hoch, S., Pino, P., Salinas, A., Rahbar, M. H., Mora, F., Cortes-Penfield, N., & McCormick, J. (2008a). Tuberculosis in poorly controlled type 2 diabetes: Altered cytokine expression in peripheral white blood cells. Clinical Infectious Diseases, 47, 634–641.

    Article  CAS  PubMed  Google Scholar 

  • Restrepo, B. I., Fisher-Hoch, S., Smith, B., Jeon, S., Rahbar, M. H., & McCormick, J. (2008b). Mycobacterial clearance from sputum is delayed during the first phase of treatment in patients with diabetes. The American Journal of Tropical Medicine and Hygiene, 79, 541–544.

    Article  PubMed  Google Scholar 

  • Restrepo, B. I., Camerlin, A. J., Rahbar, M. H., Wang, W., Restrepo, M. A., Zarate, I., Mora-Guzman, F., Crespo-Solis, J. G., Briggs, J., McCormick, J. B., et al. (2011). Cross-sectional assessment reveals high diabetes prevalence among newly-diagnosed tuberculosis cases. Bulletin of the World Health Organization, 89, 352–359.

    Article  PubMed  PubMed Central  Google Scholar 

  • Restrepo, B. I., Twahirwa, M., Rahbar, M. H., & Schlesinger, L. S. (2014). Phagocytosis via complement or Fc-gamma receptors is compromised in monocytes from type 2 diabetes patients with chronic hyperglycemia. PLoS One, 9, e92977.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ronacher, K., Joosten, S. A., van Crevel, R., Dockrell, H. M., Walzl, G., & Ottenhoff, T. H. (2015). Acquired immunodeficiencies and tuberculosis: Focus on HIV/AIDS and diabetes mellitus. Immunological Reviews, 264, 121–137.

    Article  CAS  PubMed  Google Scholar 

  • Root, H. (1934). The association of diabetes and tuberculosis. New England Journal of Medicine, 210, 1–13.

    Article  Google Scholar 

  • Russell, D. G. (2007). Who puts the tubercle in tuberculosis? Nature Reviews. Microbiology, 5, 39–47.

    Article  CAS  PubMed  Google Scholar 

  • Shah, B. R., & Hux, J. E. (2003). Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care, 26, 510–513.

    Article  PubMed  Google Scholar 

  • Silwer, H., & Oscarsson, P. N. (1958). Incidence and coincidence of diabetes mellitus and pulmonary tuberculosis in a Swedish county. Acta Medica Scandinavica. Supplementum, 335, 1–48.

    CAS  PubMed  Google Scholar 

  • Singhal, A., Jie, L., Kumar, P., Hong, G. S., Leow, M. K., Paleja, B., Tsenova, L., Kurepina, N., Chen, J., Zolezzi, F., et al. (2014). Metformin as adjunct antituberculosis therapy. Science Translational Medicine, 6, 263ra159.

    Article  PubMed  CAS  Google Scholar 

  • Stalenhoef, J. E., Alisjahbana, B., Nelwan, E. J., van der Ven-Jongekrijg, J., Ottenhoff, T. H., van der Meer, J. W., Nelwan, R. H., Netea, M. G., & van Crevel, R. (2008). The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus. European Journal of Clinical Microbiology & Infectious Diseases, 27, 97–103.

    Article  CAS  Google Scholar 

  • Stevenson, C. R., Critchley, J. A., Forouhi, N. G., Roglic, G., Williams, B. G., Dye, C., & Unwin, N. C. (2007a). Diabetes and the risk of tuberculosis: A neglected threat to public health? Chronic Illness, 3, 228–245.

    Article  PubMed  Google Scholar 

  • Stevenson, C. R., Forouhi, N. G., Roglic, G., Williams, B. G., Lauer, J. A., Dye, C., & Unwin, N. (2007b). Diabetes and tuberculosis: The impact of the diabetes epidemic on tuberculosis incidence. BMC Public Health, 7, 234.

    Article  PubMed  PubMed Central  Google Scholar 

  • Stirban, A., Gawlowski, T., & Roden, M. (2014). Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms. Molecular Metabolism, 3, 94–108.

    Article  CAS  PubMed  Google Scholar 

  • Su, V. Y., Su, W. J., Yen, Y. F., Pan, S. W., Chuang, P. H., Feng, J. Y., Chou, K. T., Yang, K. Y., Lee, Y. C., & Chen, T. J. (2017). Statin use is associated with a lower risk of TB. Chest, 152, 598–606.

    Article  PubMed  Google Scholar 

  • Subhash, H. S., Ashwin, I., Mukundan, U., Danda, D., John, G., Cherian, A. M., & Thomas, K. (2003). Drug resistant tuberculosis in diabetes mellitus: A retrospective study from South India. Tropical Doctor, 33, 154–156.

    Article  CAS  PubMed  Google Scholar 

  • Sun, Q., Zhang, Q., Xiao, H., Cui, H., & Su, B. (2012). Significance of the frequency of CD4+CD25+CD127- T-cells in patients with pulmonary tuberculosis and diabetes mellitus. Respirology, 17, 876–882.

    Article  PubMed  Google Scholar 

  • Tan, K. S., Lee, K. O., Low, K. C., Gamage, A. M., Liu, Y., Tan, G. Y., Koh, H. Q., Alonso, S., & Gan, Y. H. (2012). Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria. The Journal of Clinical Investigation, 122, 2289–2300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • The Diabetes Control and Complications Trial Research Group, Nathan, D. M., Genuth, S., Lachin, J., Cleary, P., Crofford, O., et al. (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England Journal of Medicine, 329, 977–986. https://doi.org/10.1056/NEJM199309303291401

    Article  Google Scholar 

  • Vallerskog, T., Martens, G. W., & Kornfeld, H. (2010). Diabetic mice display a delayed adaptive immune response to Mycobacterium tuberculosis. Journal of Immunology, 184, 6275–6282.

    Article  CAS  Google Scholar 

  • Viney, K., Brostrom, R., Nasa, J., Defang, R., & Kienene, T. (2014). Diabetes and tuberculosis in the Pacific Islands region. The Lancet Diabetes and Endocrinology, 2, 932.

    Article  PubMed  Google Scholar 

  • Viswanathan, V., Kumpatla, S., Aravindalochanan, V., Rajan, R., Chinnasamy, C., Srinivasan, R., Selvam, J. M., & Kapur, A. (2012). Prevalence of diabetes and pre-diabetes and associated risk factors among tuberculosis patients in India. PLoS One, 7, e41367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Viswanathan, V., Vigneswari, A., Selvan, K., Satyavani, K., Rajeswari, R., & Kapur, A. (2014). Effect of diabetes on treatment outcome of smear-positive pulmonary tuberculosis--a report from South India. Journal of Diabetes and its Complications, 28, 162–165.

    Article  PubMed  Google Scholar 

  • Walker, C., & Unwin, N. (2010). Estimates of the impact of diabetes on the incidence of pulmonary tuberculosis in different ethnic groups in England. Thorax, 65, 578–581.

    Article  PubMed  Google Scholar 

  • Walsh, M., Camerlin, A., Miles, R., Pino, P., Martinez, P., Mora-Guzman, F., Crespo-Solis, J., Fisher-Hoch, S., McCormick, J., & Restrepo, B. I. (2010). Sensitivity of interferon-gamma release assays is not compromised in tuberculosis patients with diabetes. The International Journal of Tuberculosis and Lung Disease, 15, 179–184.

    Google Scholar 

  • Wang, P. D., & Lin, R. S. (2001). Drug-resistant tuberculosis in Taipei, 1996-1999. American Journal of Infection Control, 29, 41–47.

    Article  CAS  PubMed  Google Scholar 

  • Wang, C. H., Yu, C. T., Lin, H. C., Liu, C. Y., & Kuo, H. P. (1999). Hypodense alveolar macrophages in patients with diabetes mellitus and active pulmonary tuberculosis. Tubercle and Lung Disease, 79, 235–242.

    Article  PubMed  Google Scholar 

  • Webb, E. A., Hesseling, A. C., Schaaf, H. S., Gie, R. P., Lombard, C. J., Spitaels, A., Delport, S., Marais, B. J., Donald, K., Hindmarsh, P., et al. (2009). 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, 13, 868–874.

    CAS  PubMed  Google Scholar 

  • Yamashiro, S., Kawakami, K., Uezu, K., Kinjo, T., Miyagi, K., Nakamura, K., & Saito, A. (2005). Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with Mycobacterium tuberculosis. Clinical and Experimental Immunology, 139, 57–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhan, Y., & Jiang, L. (2015). Status of vitamin D, antimicrobial peptide cathelicidin and T helper-associated cytokines in patients with diabetes mellitus and pulmonary tuberculosis. Experimental and Therapeutic Medicine, 9, 11–16.

    Article  CAS  PubMed  Google Scholar 

  • Zumla, A., Rao, M., Parida, S. K., Keshavjee, S., Cassell, G., Wallis, R., Axelsson-Robertsson, R., Doherty, M., Andersson, J., & Maeurer, M. (2015). Inflammation and tuberculosis: Host-directed therapies. Journal of Internal Medicine, 277, 373–387.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UTHealth Houston, School of Public Health, Brownsville, TX, USA

    Blanca I. Restrepo

Authors
  1. Blanca I. Restrepo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Blanca I. Restrepo .

Editor information

Editors and Affiliations

  1. Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA, USA

    Vishwanath Venketaraman

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Restrepo, B.I. (2018). Diabetes and Tuberculosis. In: Venketaraman, V. (eds) Understanding the Host Immune Response Against Mycobacterium tuberculosis Infection. Springer, Cham. https://doi.org/10.1007/978-3-319-97367-8_1

Download citation

Publish with us

Policies and ethics

Search

Navigation