Whole RNA profiling of Tuberculosis-diabetes comorbidity linked to diabetes with poor glycemic control
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PROVIDER: PRJNA1047166 | ENA |
REPOSITORIES: ENA
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Project description:Type 2 diabetes (DM2) is a disease that hinders tuberculosis (TB) control strategies worldwide. TB infection, progression, morbidity, treatment success, adverse effects, relapse, and mortality are worse in these susceptible populations. Therefore, expanding the partially known molecular mechanisms leading to TB-DM2 comorbidity may be essential to face both epidemics. Consequently, a transcriptomic study was conducted on TB-DM2 comorbidity, associated with patients with DM2 who have poor glycaemic control (PDM2), since they have a higher risk of getting TB. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), TB ( HbA1c < 6.5%), TB-DM2, DM2 (HbA1c < 8.9%), and PDM2 (HbA1c > 10%) groups (n=4 each) were analyzed using high-density human GE 4X44K v2 differential expression microarrays.
2024-06-04 | GSE249102 | GEO
Project description:The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
2016-07-15 | ST000421 | MetabolomicsWorkbench
Project description:Diabetes mellitus is associated with serious long-term complications, including increased cardiovascular risk and a higher occurrence of infections. These diabetes-related complications are suggestive of altered responses of the innate immune system. Recent studies have shown that energy metabolism of monocytes is a crucial determinant of their functionality. Here we investigate whether metabolism and function of monocytes are changed in patients with diabetes and aim to identify diabetes-associated factors driving these alterations. Patients with type 1 diabetes (T1D) and healthy age-, sex- and BMI-matched nondiabetic controls were recruited and detailed characteristics related to disease status including diabetes duration and glycemic burden (HbA1c levels) were collected. Monocytes were isolated from peripheral blood to determine immune functionality, metabolic responses and to perform transcriptome analyses. Upon ex vivo stimulation with TLR-4 agonist LPS or TLR-2 agonist P3C, monocytes of patients with T1D secreted lower levels of various cytokines (TNFα, IL-1β and IL-1Ra) and had lower glycolytic rates in comparison to monocytes isolated from matched controls. Stratification based on HbA1c levels revealed that a lower cytokine secretion was coupled to a higher glycolytic rate of monocytes in patients with a higher glycemic burden. Gene expression signatures of circulating monocytes displayed an enhanced inflammatory expression pattern that was associated with this high glycemic burden. A high glycemic burden in patients with T1D promotes expression of inflammatory genes of monocytes in vivo and is coupled to an impaired relationship between metabolism and inflammatory function upon activation ex vivo.
2020-10-09 | GSE154609 | GEO
Project description:Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity
| PRJNA798677 | ENA
Project description:The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
2016-07-01 | ST000422 | MetabolomicsWorkbench
Project description: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.
2023-09-05 | GSE193978 | GEO
Project description:Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-lipoxygenase (12/15-LOX) is induced in β cells and macrophages during T1D and produces pro-inflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency. Only ML351 exhibited no apparent toxicity across a range of concentrations in mouse islets, and molecular modeling suggested reduced promiscuity of ML351 compared to ML127. In mouse islets, incubation with ML351 improved glucose-stimulated insulin secretion in the presence of pro-inflammatory cytokines and triggered gene expression pathways responsive to oxidative stress and cell death. Consistent with a role for 12/15-LOX in promoting oxidative stress, its chemical inhibition reduced production of reactive oxygen species in both mouse and human islets in vitro. In a streptozotocin-induced model of T1D in mice, ML351 prevented the development of diabetes, with coincident enhancement of nuclear Nrf2 in islet cells, reduced β-cell oxidative stress, and preservation of β-cell mass. In the non-obese diabetic mouse model of T1D, administration of ML351 during the prediabetic phase prevented dysglycemia, reduced β-cell oxidative stress, and increased the proportion of anti-inflammatory macrophages in the insulitis. Our data provide the first evidence to date that small molecules that target 12/15-LOX can prevent progression of β-cell dysfunction and glycemic deterioration in models of T1D.
2017-10-29 | GSE101722 | GEO
Project description:We assessed the effect of dietary glycemic load on miRNA expression in a sample of healthy, premenopausal women participating in a 12 month intervention designed to lower dietary glycemic load. Comparing post-intervention to baseline miRNA expression data of 14 participants receiving the active intervention.
2011-12-19 | E-GEOD-27474 | biostudies-arrayexpress
Project description:Inter-tissue communication is a fundamental feature of systemic metabolic regulation and the liver is central to this process. We have identified sparc-related modular calcium-binding protein 1 (SMOC1) as a glucose-responsive hepatokine and potent regulator of glucose homeostasis. Acute administration of recombinant SMOC1 improves glycemic control and insulin sensitivity, independent of changes in insulin secretion. SMOC1 exerts its favourable glycemic effects by inhibiting cAMP-PKA-CREB signaling in the liver, leading to decreased gluconeogenic gene expression and suppression of hepatic glucose output. Over expression of SMOC1 in the liver or once-weekly injections of a stabilized SMOC1-FC fusion protein induces durable improvements in glucose tolerance and insulin sensitivity in db/db mice, without significant adverse effects on adiposity, liver histopathology or inflammation. Furthermore, SMOC1 correlates with systemic insulin sensitivity and is decreased in obese, insulin resistant humans. Together, these findings identify SMOC1 as a potential pharmacological target for the management of glycemic control in type 2 diabetes.
2020-08-21 | PXD015767 | Pride
Project description:A high glycemic burden drives functional and metabolic alterations of human monocytes in patients with type 1 diabetes
| PRJNA646775 | ENA