Tuberculosis (TB) significantly impacts blood glucose regulation, often resulting in impaired glucose tolerance and hyperglycemia during active infection. While successful TB treatment can normalize blood glucose levels, individuals remain at increased risk for developing type 2 diabetes mellitus (T2DM) later in life. Hyperglycemia in TB patients arises from a combination of stress responses, chronic inflammation, altered glucose and lipid metabolism, and insulin resistance (IR). These immunometabolic disturbances are driven by increased inflammatory activity, changes in adipose tissue function, and elevated free fatty acids, which promote insulin resistance and can predispose individuals to T2DM if not properly managed. Reports indicate that hyperglycemia occurs in 10% to 26% of TB patients, with variations influenced by factors such as age, sex, and baseline fasting blood glucose levels.[1]
The relationship between TB and lipid metabolism is central to the development of insulin resistance. TB infection disrupts normal lipid handling, increasing circulating free fatty acids and leading to ectopic lipid deposits in organs crucial for glucose regulation, including the liver and skeletal muscle. This dysregulation contributes to the onset of IR. Additionally, TB patients often exhibit abnormal lipid profiles, such as elevated low-density lipoprotein (LDL) cholesterol, decreased high-density lipoprotein (HDL) cholesterol, and increased very low-density lipoprotein (VLDL) triglycerides. The inflammatory environment during TB infection exacerbates irregular lipolysis and alters lipid and glucose metabolism within adipose tissue and other organs, including the lungs. These changes further impair metabolic balance and insulin sensitivity.[1]
The co-occurrence of TB and diabetes mellitus (DM), or insulin resistance, presents serious clinical challenges. Metabolic dysfunction and immune system impairments in diabetic individuals worsen TB outcomes, increasing the risk of multi-drug-resistant TB (MDR-TB) and complicating treatment responses. In diabetic patients, immune deficiencies—such as impaired bacterial recognition, reduced phagocytic activity, diminished chemokine and cytokine responses, and weakened T-cell function—undermine the body's ability to control Mycobacterium tuberculosis infection. This leads to higher bacterial loads and more severe disease in organs like the lungs and liver. Diabetic individuals with latent TB infections also exhibit heightened inflammatory responses, suggesting that diabetes modulates immune signaling to mycobacterial antigens. These intertwined metabolic and immune dysfunctions highlight the clinical importance of managing both TB and DM/IR concurrently to prevent T2DM progression and improve TB treatment outcomes. Understanding these interactions is essential for addressing the dual burden of TB and diabetes in vulnerable populations.[1]
A study in Chennai, India, conducted between 2014 and 2019, followed adults aged 25 to 60 years with pulmonary tuberculosis (TB) confirmed by sputum culture. Participants were recruited from ten government TB clinics and monitored for changes in glycemic status during and after TB treatment. Median A1C levels declined across all glycemic groups during treatment, with the greatest reduction seen in the intensive phase. The new-DM group had the steepest initial drop in A1C, from 10.0% to 7.5% by month three, though levels rose again afterward. Known-DM participants showed a similar but more stable decline. No participants with normoglycemia (NG) or prediabetes (pre-DM) progressed to diabetes mellitus (DM) by months 12 or 18, and most pre-DM participants reverted to NG status. Additionally, 15.1% of known-DM participants reverted to pre-DM or NG by the end of follow-up.[2]
The study found no clear long-term benefit of antidiabetic treatment on A1C trends. Participants who never received treatment showed the greatest decrease in A1C over time. In new-DM participants who started antidiabetic medications, A1C initially dropped but later increased above 8%. Among 339 participants with recorded TB outcomes, there were 21 treatment failures, 12 recurrences, and 14 deaths. Non-adherence to TB medication was associated with a higher rate of unfavorable outcomes, while DM participants showed a non-significant trend toward better treatment adherence.[2]
Logistic regression analysis revealed that rising A1C levels after month three, particularly in DM and pre-DM groups, were linked to adverse TB outcomes. In contrast, DM participants who achieved TB cure showed greater A1C improvement over time. There was no evidence of progression to DM in those with NG or pre-DM at TB diagnosis. However, the unique glycemic patterns in new-DM participants suggest some may have had undiagnosed DM prior to their TB diagnosis. The study concluded that TB and its treatment significantly affect glycemic control, and despite antidiabetic interventions, there was no consistent long-term glycemic benefit.[2]
References:
1. 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.
2. 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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