The effect of a structured clinical algorithm on glycemic control in patients with combined tuberculosis and diabetes in Indonesia: A randomized trial

Ruslami, Rovina; Koesoemadinata, Raspati C; Soetedjo, Nanny Natalia Mulyani; Imaculata, Sofia; Gunawan, Yuanita; Permana, Hikmat; Santoso, Prayudi; Alisjahbana, Bachti; McAllister, Susan; Grint, Daniel; Critchley, Julia; Hill, Philip C.; Crevel, Reinout van

doi:10.1016/j.diabres.2021.108701

Cited by 7 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients for whom the outcome data were missing were not included in downstream analyses. Most TB-DM patients received local standard of care DM treatment following national guidelines outside of the TANDEM study, which largely involved metformin and glibenclamide prescription, whilst a subgroup in Indonesia received more intensive education and counselling, glucose and HbA1c monitoring and treatment adjustment through TB treatment as part of a pragmatic randomised control trial, 34 in which they were assessed at weeks 1, 2 and 4 and then monthly throughout TB treatment, and treatment optimised at each visit, leading to better HbA1c control at 6 months in this group.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

et al. 2022

Self Cite

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

et al. 2022

Self Cite

View full text Add to dashboard Cite

“…Most TB-DM patients received local standard of care DM treatment, whilst a subgroup in Indonesia received more intensive HbA1c monitoring and treatment adjustment through TB treatment as part of a pragmatic randomised control trial. 34…”

Section: Study Participant Recruitment Classification and Treatmentmentioning

confidence: 99%

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

Doorn

Eckold

Ronacher

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background Globally, the anti-tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success is lower among people with diabetes mellitus (DM). Predicting treatment failure early after diagnosis would allow early treatment adaptation and may improve global TB control. Methods Samples were collected in a longitudinal cohort study of adult TB patients with or without concomitant DM from South Africa and Indonesia to characterize whole blood transcriptional profiles before and during anti-TB treatment, using unbiased RNA-Seq and targeted gene dcRT-MLPA. Findings We report differences in whole blood transcriptome profiles, which were observed before initiation of treatment and throughout treatment, between patients with a good versus poor anti-TB treatment outcome. An eight-gene and a 22-gene blood transcriptional signature distinguished patients with a good treatment outcome from patients with a poor treatment outcome at diagnosis (AUC=0.815) or two weeks (AUC=0.834) after initiation of anti-TB treatment, respectively. High accuracy was obtained by cross-validating this signature in an external cohort (AUC=0.749). Interpretation These findings suggest that transcriptional profiles can be used as a prognostic biomarker for treatment failure and success, even in patients with concomitant DM. Funding The research leading to these results, as part of the TANDEM Consortium, received funding from the European Community's Seventh Framework Programme (FP7/2007-2013 Grant Agreement No. 305279) and the Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038).

show abstract

“…Most patients diagnosed with DM received local standard of care treatment, and medication taken was noted. A TB-DM subgroup within the Indonesian cohort had intensive HbA1c monitoring as part of a pragmatic randomised control trial, with DM medication changed accordingly [27]. Participants were classified by DM/glycaemia status at TB diagnosis and after 6 months TB treatment (Supplementary Table S1).…”

Section: Patient Recruitment and Classificationmentioning

confidence: 99%

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity

Eckold

Doorn

Ruslami

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

The effect of a structured clinical algorithm on glycemic control in patients with combined tuberculosis and diabetes in Indonesia: A randomized trial

Cited by 7 publications

References 25 publications

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity

Contact Info

Product

Resources

About