A collaborative study conducted by the A*STAR Infectious Diseases Labs (A*STAR ID Labs) and the University of Massachusetts (UMass) Chan Medical School has revealed that elevated levels of glycerol in the blood are associated with increased severity of tuberculosis (TB) in individuals with type 2 diabetes (T2D). This research provides valuable insight into the interaction between these two diseases and identifies glycerol levels and an enzyme involved in glycerol metabolism as potential targets for therapeutic intervention. The findings of the study were published in the journal Nature Communications.
TB is a major cause of death worldwide, resulting in 1.3 million fatalities in 2022 alone. The Asian region bears a significant burden of TB, accounting for over 65% of newly diagnosed cases globally. Singapore, in particular, has a high prevalence of TB, with latent TB infection affecting up to 30% of older age groups. In 2022, there were 1,251 new cases of active TB reported among Singapore residents. T2D is also highly prevalent in Asia and is on the rise in Singapore, with individuals suffering from T2D experiencing higher mortality rates due to TB.
Furthermore, T2D patients are more likely to experience TB relapse after completing treatment, with a four-fold increased risk for regular relapse and a two-fold increased risk for multidrug-resistant TB (MDR-TB). Despite these concerning statistics, the underlying mechanisms behind the interaction between T2D and TB have remained poorly understood.
The recent study sheds light on the molecular mechanisms underlying the exacerbated TB disease observed in experimental models with T2D. The researchers found that T2D led to higher bacterial load in the lungs, tissue damage, and increased mortality when the animals were infected with Mycobacterium tuberculosis (Mtb), the bacterium responsible for causing TB. Notably, the study identified elevated blood glycerol as a critical factor influencing the interaction between T2D and TB. In experiments where the ability of Mtb to utilize glycerol for metabolism was blocked by deleting an enzyme called glycerol kinase, the severity of lung damage was significantly reduced.
These findings suggest that Mtb relies on glycerol as a nutrient source to drive the severity of TB disease in individuals with T2D. Consequently, individuals with T2D are more susceptible to TB because Mtb can utilize the excess glycerol present in their blood and bodies, leading to more severe disease progression.
The discovery of the role of glycerol in TB-T2D interactions represents a significant breakthrough in our understanding of these diseases. It highlights glycerol as a potential therapeutic target for the treatment of TB in individuals with T2D. This could pave the way for the development of innovative host-directed therapeutics, which are crucial for addressing the heightened susceptibility of T2D populations to TB, especially in the face of increasing resistance to TB drugs. As the prevalence of TB continues to rise globally, understanding its interactions with other diseases becomes an urgent priority in global health.
Dr. Amit Singhal, Senior Principal Investigator at A*STAR ID Labs and co-senior author of the study, remarked, “Our findings establish a link between TB severity in T2D and glycerol levels, a factor that has not been considered in clinical studies thus far. Furthermore, it underscores the importance of Mtb’s glycerol kinase as a potential target for TB drug development, which could expand our arsenal against antibiotic-resistant bacteria.”
Dr. Hardy Kornfeld, Professor at UMass and co-senior author of the study, added, “It is well-known that individuals with type 2 diabetes have a three-fold increased risk of developing TB. The discovery of the association between glycerol levels and this interaction is exciting and opens up avenues for the design of potential novel therapeutic strategies against TB.”
Prof. Lisa Ng, Executive Director at A*STAR ID Labs, emphasized the significance of the study, stating, “This study sheds light on how TB interacts with other chronic diseases such as diabetes. This knowledge is crucial for the future of healthcare in Singapore, given the projected increase in the number of diabetics in the country.”
In conclusion, the study’s findings linking blood glycerol levels to the severity of TB in individuals with T2D showcase the potential for targeting glycerol metabolism as a therapeutic strategy. This research not only enhances our understanding of the interaction between TB and T2D but also presents new avenues for the development of effective treatments for patients with these conditions.
1. Source: Coherent Market Insights, Public sources, Desk research
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