Tuberculosis as Complication of Diabetes Mellitus

Gauld, W. R.; Lyall, Alexander

doi:10.1136/bmj.1.4506.677

Cited by 12 publications

(7 citation statements)

References 3 publications

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“…Epidemiologic studies indicate that diabetes mellitus (DM) is a significant risk factor for both acquisition of TB disease and increased disease severity . The original observations were noted more than half a century ago, but concerns have been heightened recently due to the rising rates of Type II DM worldwide . In a systematic review of observational studies with age‐adjusted estimates of the association of DM with active TB disease, 13 studies were identified with 1 786 212 participants and 17 698 cases of TB .…”

Section: Got Balance? Establishing Effective Anti‐tb Immunity By Targmentioning

confidence: 99%

New tricks for old dogs: countering antibiotic resistance in tuberculosis with host‐directed therapeutics

Hawn

Shah

Kalman

2015

Immunological Reviews

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Summary Despite the availability of Mycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis (TB) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of the disease, especially for treatment during human immunodeficiency virus co-infection. One solution to the conundrum that antibiotics kill the bacillus yet select for resistance is to target the host rather than the pathogen. Here we discuss recent progress in so called ‘host-directed therapeutics’ (HDTs), focusing on two general mechanistic strategies: (i) HDTs that disrupt Mtb pathogenesis in macrophages and (ii) immunomodulatory HDTs that facilitate protective immune responses that kill Mtb or reduce deleterious responses that exacerbate disease. HDTs hold significant promise as adjunctive therapies in that they are less likely to engender resistance, will likely have efficacy against antibiotic-resistant strains, and may have activity against non-replicating Mtb. However, TB is a complex and variegated disease, and human populations exhibit significant diversity in their immune responses to it, which presents a complicated landscape for HDTs to navigate. Nevertheless, we suggest that a detailed mechanistic understanding of drug action, together with careful selection of disease stage targets and dosing strategies may overcome such limitations and allow the development of HDTs as effective adjunctive treatment options for TB.

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Section: Got Balance? Establishing Effective Anti‐tb Immunity By Targmentioning

confidence: 99%

New tricks for old dogs: countering antibiotic resistance in tuberculosis with host‐directed therapeutics

Hawn

Shah

Kalman

2015

Immunological Reviews

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“…Specifically, the HIV epidemic has highlighted T cell function as an important component of immune protection. Besides HIV, there remains many other significant conditions in which the risk of Mtb acquisition and or progression from latent infection to active disease is increased (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Diabetes as an epidemiological risk factor for TB is wellreported (13). Spanning back to 1947, a review of diabetes and Mtb co-infection reported that 50% of diabetics succumbed to pulmonary TB (10). In recent years the epidemic has grown, with the number of individuals with Diabetes-TB overtaking those with HIV-TB (14); which can be attributed in part, to the positive impacts that antiretroviral therapy is having on reducing TB-HIV co-infection (15).…”

Section: Introductionmentioning

confidence: 99%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with proinflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

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“…An adverse effect of diabetes mellitus (DM) on the host defense against tuberculosis (TB) has been recognized for over a century but has only recently been investigated in detail as DM rates have increased dramatically since the 1980s in low‐ and middle‐income countries where TB is already prevalent . Insulin‐resistant type 2 DM comprises 90% of the global cases of DM and a large proportion of the people afflicted with the dual TB/DM burden ; however autoimmune type 1 DM is also associated with TB susceptibility . This is unsurprising since both types of DM share a similar spectrum of other complications that develop as a consequence of chronic hyperglycemia .…”

Section: Introductionmentioning

confidence: 99%

Diabetes and immunity to tuberculosis

2014

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Summary The dual burden of tuberculosis and diabetes has attracted much attention in the past decade as diabetes prevalence has increased dramatically in countries already afflicted with a high burden of tuberculosis. The confluence of these two major diseases presents a serious threat to global public health; at the same time it also presents an opportunity to learn more about the key elements of human immunity to tuberculosis that may be relevant to the general population. Some effects of diabetes on innate and adaptive immunity which are potentially relevant to tuberculosis defense have been identified, but have yet to be verified in humans and are unlikely to fully explain the interaction of these two disease states. This review provides an update on the clinical and epidemiological features of tuberculosis in the diabetic population and relates them to recent advances in understanding the mechanistic basis of tuberculosis susceptibility and other complications of diabetes. Issues that merit further investigation, such as geographic host and pathogen differences in the diabetes/tuberculosis interaction, the role of hyperglycemia-induced epigenetic reprogramming in immune dysfunction and the impact of diabetes on lung injury and fibrosis caused by tuberculosis, are highlighted in this review.

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Tuberculosis as Complication of Diabetes Mellitus

Cited by 12 publications

References 3 publications

New tricks for old dogs: countering antibiotic resistance in tuberculosis with host‐directed therapeutics

New tricks for old dogs: countering antibiotic resistance in tuberculosis with host‐directed therapeutics

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

Diabetes and immunity to tuberculosis

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