Glycemic Trajectories and Treatment Outcomes of Patients with Newly Diagnosed Tuberculosis: A Prospective Study in Eastern China

Liu, Qiao; You, Nannan; Pan, Hongqiu; Shen, Ye; Lü, Peng; Wang, Jianming; Lü, Wei; Zhu, Limei; Martínez, Leonardo

doi:10.1164/rccm.202007-2634oc

Cited by 24 publications

(29 citation statements)

References 34 publications

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“…tuberculosis [36], and has been suggested as adjunctive therapy for TB, particularly in patients with diabetes [37]. Our transcriptomic data suggest that patients with either pre-diabetes or TB-related IH would also benefit from prolonged or adjunctive host-directed therapy, in alignment with observed worse TB treatment outcomes in people with transient hyperglycaemia [38].…”

Section: Discussionmentioning

confidence: 82%

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity

Eckold

Doorn

Ruslami

et al. 2022

Preprint

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Background People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB-diabetes (TB-DM) co-morbidity have excessive inflammatory and reduced interferon responses at TB diagnosis. It is unknown whether this persists through treatment, potentially underlying adverse outcomes. Methods Pulmonary TB patients were recruited in South Africa, Indonesia and Romania, and classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or uncomplicated TB, based on glycated haemoglobin (HbA1c) concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood samples collected at diagnosis and at regular intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification. Results Gene expression was modulated by TB treatment in all groups but to different extents, such that differences remained in people with TB-DM relative to TB-only throughout, including genes involved in innate responses, anti-microbial immunity and the inflammasome. People with prediabetes or with TB-related hyperglycaemia had gene expression more similar to people with TB-DM than TB-only throughout treatment. The overall pattern of change was similar across clinical groups irrespective of glycaemic index, permitting models predictive of TB treatment to be developed. Conclusions The exacerbated transcriptome changes seen in TB-DM take longer to resolve during TB treatment, indicating that prolonged treatment or host-directed therapy may be needed to improve TB treatment outcomes. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes to be useful across populations.

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Section: Discussionmentioning

confidence: 82%

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity

Eckold

Doorn

Ruslami

et al. 2022

Preprint

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“…This is in contrast with work by Liu and colleagues who demonstrated improved outcome prediction by using glycemic trajectories as a predictor rather than a simple diabetes diagnosis dichotomy. 4 There are several limitations to this work. First, as this cohort represents programmatically available data, there are several clinical indicators of disease severity that were not available or had high degrees of missingness.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Increasingly popular methods exist which can assess entire longitudinal trajectories and this trajectory-based approach has been shown to improve outcome prediction relative to single summary measures in TB 4 and other health conditions. 5,6 Here, we apply a trajectory-based analysis to characterize adherence behavior early in DR TB treatment and assess whether these patterns predict treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Adherence trajectory as an on-treatment risk indicator among drug-resistant TB patients in the Philippines

Huddart

Geocaniga-Gaviola

Crowder

et al. 2022

Preprint

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IntroductionHigh levels of treatment adherence are critical for achieving optimal treatment outcomes among patients with tuberculosis (TB), especially for drug-resistant TB (DR TB). Current tools for identifying high-risk non-adherence are insufficient. Here, we apply trajectory analysis to characterize adherence behavior early in DR TB treatment and assess whether these patterns predict treatment outcomes.MethodsWe conducted a retrospective analysis of Philippines DR TB patients treated between 2013 and 2016. To identify unique patterns of adherence, we performed group-based trajectory modelling on adherence to the first 12 weeks of treatment. We estimated the association of adherence trajectory group with six-month and final treatment outcomes using univariable and multivariable logistic regression. We also estimated and compared the predictive accuracy of adherence trajectory group and a binary adherence threshold for treatment outcomes.ResultsOf 596 patients, 302 (50.7%) had multidrug resistant TB, 11 (1.8%) extremely drug-resistant (XDR) TB, and 283 (47.5%) pre-XDR TB. We identified three distinct adherence trajectories during the first 12 weeks of treatment: a high adherence group (n=483), a moderate adherence group (n=93) and a low adherence group (n=20). Similar patterns were identified at 4 and 8 weeks. Being in the 12-week moderate or low adherence group was associated with unfavorable six-month (adjusted OR [aOR] 3.42, 95% CI 1.90 - 6.12) and final (aOR 2.71, 95% 1.73 - 4.30) treatment outcomes. Adherence trajectory group performed similarly to a binary threshold classification for the prediction of final treatment outcomes (65.9 % vs. 65.4 % correctly classified), but was more accurate for prediction of six-month treatment outcomes (79.4% vs. 60.0% correctly classified).ConclusionsAdherence patterns are strongly predictive of patient treatment outcomes. Trajectory-based analyses represent an exciting avenue of research into TB patient adherence behavior seeking to inform interventions which rapidly identify and support patients with high-risk adherence patterns.

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“…In this issue of the Journal , Liu and colleagues (pp. 347–356 ) have added additional nuance to the relationship between DM and TB ( 3 ). The authors measured fasting plasma glucose (FPG) serially among 405 patients with newly diagnosed TB in China at the time of diagnosis, the third and sixth month of treatment, and at 2 and 4 months after treatment completion.…”

mentioning

confidence: 99%

Is Glycemic Control the Secret to Tuberculosis Control?

Huddart

Savic

Cattamanchi

2021

Am J Respir Crit Care Med

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Glycemic Trajectories and Treatment Outcomes of Patients with Newly Diagnosed Tuberculosis: A Prospective Study in Eastern China

Cited by 24 publications

References 34 publications

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity

Adherence trajectory as an on-treatment risk indicator among drug-resistant TB patients in the Philippines

Is Glycemic Control the Secret to Tuberculosis Control?

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