Analytical Exploration of Potential Pathways by which Diabetes Mellitus Impacts Tuberculosis Epidemiology.
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ABSTRACT:
SUBMITTER: Awad SF
PROVIDER: S-EPMC6560095 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine the prevalence and determinants of diabetes mellitus (DM) among tuberculosis (TB) patients and to assess the additional yield and number needed to screen (NNS) to obtain a newly diagnosed DM among TB patients.DesignWe undertook a cross-sectional analysis of the cohort data under Regional Prospective Observational Research for Tuberculosis-India consortium. Newly diagnosed TB patients recruited into the cohort between 2014 and 2018 were included. Pretested standardised questionnaires and tools were used for data collection. Prevalence of DM among TB patients was summarised as proportion with 95% CI. Type II DM was diagnosed if random blood sugar level was >200 mg/dL or if the participant had a documented history of DM. NNS by blood glucose testing to diagnose one new DM case among TB patients was also calculated.SettingThree districts of South India: Puducherry, Cuddalore and Villupuram SUBJECTS: Newly diagnosed sputum smear positive pulmonary TB patients aged ≥16 years RESULTS: In total, 1188 TB patients were included. Prevalence of DM among TB patients was 39% (95% CI: 36.2% to 41.8%). In unadjusted analysis, elderly TB, marital status, caste, gender, higher education level, household income and obesity had a significant association with DM. However, in adjusted analysis, only marital status (currently married aPR; 3.77 (95 CI: 2.20 to 6.49), widowed/separated/divorced aPR; 3.66 (95 CI: 1.96 to 6.83)) and body mass index category (normal weight aPR; 3.26 (95 CI: 2.55 to 4.16), overweight aPR; 3.86 (95 CI: 2.69 to 5.52), obesity aPR; 4.08 (95 CI: 2.81 to 5.94)) were found to be significant determinants. The number of TB patients needed to be screened to find a new DM case was 12.ConclusionWe found that one in three TB patients had coexisting DM. The number of TB patients needed to be screened to obtain a newly diagnosed DM patients was also determined. The study supports and highlights the need of RNTCP's effort in bidirectional screening of TB and DM.
| S-EPMC8543642 | biostudies-literature
Project description:BackgroundThere is scarce evidence that tuberculosis (TB) can cause diabetes in those not previously known to be diabetic. Whilst the World Health Organization (WHO) recommends screening for Diabetes Mellitus (DM) at the onset of TB treatment, nevertheless, it remains to be elucidated which patients with TB-associated hyperglycemia are at higher risk for developing DM and stand to benefit from a more regular follow-up. This review aims to firstly quantify the reduction of newly detected hyperglycemia burden in TB patients who are on treatment over time; secondly, determine the burden of TB-associated hyperglycemia after follow-up, and thirdly, synthesize literature on risk factors for unresolved TB-associated hyperglycemia in previously undiagnosed individuals.MethodsWe searched PUBMED, EMBASE, SCOPUS, and Global Health for articles on TB-associated hyperglycemia up to September 30th, 2019. Search terms included Tuberculosis and hyperglycemia/DM, and insulin resistance. We appraised studies, extracted data, and conducted a meta-analysis to assess the change of the burden of hyperglycemia in prospective studies. The review is registered in the PROSPERO database (CRD42019118173).ResultsEleven studies were included in the meta-analysis yielding a total of 677 (27,3%) of patients with newly detected hyperglycemia at baseline. The mean quality score of eligible studies using the Newcastle-Ottawa Quality Assessment Scale was 7.1 out of 9 (range 6-9). The pooled unresolved new cases of hyperglycemia at the end of follow up was 50% (95% CI: 36-64%) and the total pooled burden of hyperglycemia at 3-6 months of follow up was 11% (95% CI: 7-16%), with both estimates displaying a high heterogeneity, which remained significant after performing a sub-analysis by DM diagnostic method and 3 months of follow up. As only 2 studies explored risk factors for unresolved hyperglycemia, no meta-analysis was performed on risk factors.ConclusionOur meta-analysis showed that although in half of the patients with newly observed hyperglycemia at baseline, it remained unresolved at a follow-up of 3 to 6 months, the total burden of hyperglycemia is slightly above 10%, 3 months after initiating TB treatment. Studies are warranted to assess whether risk factors including HIV positivity, smoking, and extensive pulmonary TB disease put patients at higher risk for DM.
| S-EPMC7724718 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that has turned up as pandemic dimensions all over the world. In China, some traditional Chinese herbal formulas have enjoyed a high reputation in T2DM treatment for centuries. And ShenQi compound (SQC), a formula has been performed on T2DM clinical therapeutics in China for many years, deserve to study in depth. Gene microarray experiments were performed to explore the molecular mechanism of SQC treatment. In addition, a western medicine, metformin was employed as a comparison.
2021-01-22 | GSE165225 | GEO
Project description:In many low- and middle-income countries (LMICs), the epidemiological transition is characterized by an increased burden of non-communicable diseases (NCDs) and the persistent challenge of infectious diseases. The transmission of tuberculosis, one of the leading infectious diseases, can be halted through active screening of risk groups and early case findings. Studies have reported comorbidities between tuberculosis (TB) and NCDs, which necessitates the development of an integrated disease management model. This scoping review discusses the possibilities and problems of integration in managing TB and NCDs, with a particular emphasis on diabetic mellitus (DM) and hypertension screening and control. We will conduct this review following Arksey and O'Malley's framework for scoping review. We will use key terms related to integrated management, i.e., screening, diagnosis, treatment, and care, of TB, DM, and hypertension in PubMed, Scopus Database, and ScienceDirect for research published from January 2005 to July 2021. This review will also consider grey literature, including unpublished literature and international disease management guidelines on TB, DM, and hypertension from WHO or other health professional organization. We will export the search results to citation manager software (EndNote). We will remove duplicates and apply the inclusion and exclusion criteria to identify the set of papers for the review. After screening the titles and abstract, two authors will independently review the full text of selected studies and extract the data. We will synthesize all selected studies qualitatively and the results will be discussed with the experts. The results will be used as the basis of the development of a guideline for integrated TB, DM, and hypertension management.
| S-EPMC9275721 | biostudies-literature
Project description:BackgroundDiabetes mellitus (DM) increases the risk of tuberculosis (TB) disease. Knowledge of the impact of DM on TB treatment outcomes is primarily based on retrospective studies.MethodsWe conducted a prospective cohort study of new pulmonary TB patients with and without DM (TB-DM and TB only) in India. The association of DM with a composite unfavorable TB treatment outcome (failure, recurrence, mortality) over 18 months was determined, and the effect of DM on all-cause mortality and early mortality (death during TB treatment) was assessed.ResultsOf 799 participants, 574 (72%) had TB only and 225 (28%) had TB-DM. The proportion of patients with DM who experienced the composite outcome was 20%, as compared with 21% for TB-only participants (adjusted hazard ratio [aHR], 1.13; 95% CI, 0.75-1.70). Mortality was higher in participants with DM (10% vs 7%), and early mortality was substantially higher among patients with DM (aHR, 4.36; 95% CI, 1.62-11.76).ConclusionsDM was associated with early mortality in this prospective cohort study, but overall unfavorable outcomes were similar to participants without DM. Interventions to reduce mortality during TB treatment among people with TB-DM are needed.
| S-EPMC8047862 | biostudies-literature
Project description:Molecular pathological epidemiology (MPE) is a multidisciplinary and transdisciplinary study field, which has emerged as an integrated approach of molecular pathology and epidemiology, and investigates the relationship between exogenous and endogenous exposure factors, tumor molecular signatures, and tumor initiation, progression, and response to treatment. Molecular epidemiology broadly encompasses MPE and conventional-type molecular epidemiology. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated death worldwide and remains as a major public health challenge. Over the past few decades, a number of epidemiological studies have demonstrated that diabetes mellitus (DM) is an established independent risk factor for HCC. However, how DM affects the occurrence and development of HCC remains as yet unclearly understood. MPE may be a promising approach to investigate the molecular mechanisms of carcinogenesis of DM in HCC, and provide some useful insights for this pathological process, although a few challenges must be overcome. This review highlights the recent advances in this field, including: (1) introduction of MPE; (2) HCC, risk factors, and DM as an established independent risk factor for HCC; (3) molecular pathology, molecular epidemiology, and MPE in DM and HCC; and (4) MPE studies in DM and risk of HCC. More MPE studies are expected to be performed in future and I believe that this field can provide some very important insights on the molecular mechanisms, diagnosis, personalized prevention and treatment for DM and risk of HCC.
| S-EPMC5037325 | biostudies-literature
Project description:Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are common chronic diseases that threaten human health. Patients with DM are susceptible to PTB, an important factor that aggravates the complications of diabetes. However, the molecular regulatory mechanism underlying the susceptibility of patients with DM to PTB infection remains unknown. In this study, healthy subjects, patients with primary PTB, and patients with primary PTB complicated by DM were recruited according to inclusion and exclusion criteria. Peripheral whole blood was collected, and alteration profiles and potential molecular mechanisms were further analyzed using integrated bioinformatics analysis of metabolomics and transcriptomics. Transcriptional data revealed that lipocalin 2 (LCN2), defensin alpha 1 (DEFA1), peptidoglycan recognition protein 1 (PGLYRP1), and integrin subunit alpha 2b (ITGA2B) were significantly upregulated, while chloride intracellular channel 3 (CLIC3) was significantly downregulated in the group with PTB and DM (PTB_DM) in contrast to the healthy control (HC) group. Additionally, the interleukin 17 (IL-17), phosphatidylinositol 3-kinase (PI3K)-AKT, and peroxisome proliferator-activated receptor (PPAR) signaling pathways are important for PTB infection and regulation of PTB-complicated diabetes. Metabolomic data showed that glycerophospholipid metabolism, carbon metabolism, and fat digestion and absorption processes were enriched in the differential metabolic analysis. Finally, integrated analysis of both metabolomic and transcriptomic data indicated that the NOTCH1/JAK/STAT signaling pathway is important in PTB complicated by DM. In conclusion, PTB infection altered the transcriptional and metabolic profiles of patients with DM. Metabolomic and transcriptomic changes were highly correlated in PTB patients with DM. Peripheral metabolite levels may be used as biomarkers for PTB management in patients with DM. IMPORTANCE The comorbidity of diabetes mellitus (DM) significantly increases the risk of tuberculosis infection and adverse tuberculosis treatment outcomes. Most previous studies have focused on the relationship between the effect of blood glucose control and the outcome of antituberculosis treatment in pulmonary tuberculosis (PTB) with DM (PTB_DM); however, early prediction and the underlying molecular mechanism of susceptibility to PTB infection in patients with DM remain unclear. In this study, transcriptome sequencing and untargeted metabolomics were performed to elucidate the key molecules and signaling pathways involved in PTB infection and the susceptibility of patients with diabetes to PTB. Our findings contribute to the development of vital diagnostic biomarkers for PTB or PTB_DM and provide a comprehensive understanding of molecular regulation during disease progression.
| S-EPMC10434036 | biostudies-literature
Project description:<p>Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are common chronic diseases that threaten human health. Patients with DM are susceptible to PTB, an important factor that aggravates the complications of diabetes. However, the molecular regulatory mechanism underlying the susceptibility of patients with DM to PTB infection remains unknown. Healthy subjects, patients with primary PTB and patients with primary PTB complicated by DM were recruited according to inclusion and exclusion criteria. Peripheral whole blood was collected, and alteration profiles and potential molecular mechanisms were further analyzed using integrated bioinformatics analysis of metabolomics and transcriptomics. In this study, transcriptional data revealed that lipocalin 2 (LCN2), defensin alpha 1 (DEFA1), peptidoglycan recognition protein 1 (PGLYRP1) and integrin subunit alpha 2b (ITGA2B) were significantly upregulated, while chloride intracellular channel 3 (CLIC3) significantly down-regulated in PTB-DM by contrast to HC group. Additionally, the IL-17, PI3K-AKT and PPAR signaling pathways are important for PTB infection and regulation of PTB-complicated diabetes. Metabolomic data showed that glycerophospholipid metabolism, carbon metabolism and fat digestion and absorption processes were enriched in the differential metabolic analysis. Finally, integrated analysis of both metabolomic and transcriptomic data indicated that the NOTCH1/JAK/STAT signaling pathway is important in PTB complicated by DM. In conclusion, PTB infection altered the transcriptional and metabolic profiles of patients with DM. Metabolomic and transcriptomic changes were highly correlated in PTB-infected patients with DM. Peripheral metabolite levels may be used as biomarkers for PTB management in patients with DM.</p><p><strong>IMPORTANCE:</strong> The comorbidity of diabetes mellitus (DM) significantly increases the risk of tuberculosis infection and adverse tuberculosis treatment outcomes. Most previous studies have focused on the relationship between the effect of blood glucose control and the outcome of anti-tuberculosis treatment in pulmonary tuberculosis (PTB)-DM; however, early prediction and the underlying molecular mechanism of susceptibility to PTB infection in patients with DM remain unclear. Here, transcriptome sequencing and untargeted metabolomics were performed to elucidatethe key molecules and signaling pathways involved in PTB infection and the susceptibility of patients with diabetes to PTB. Our findings contribute to the development of vital diagnostic biomarkers for PTB or PTB-DM and provide acomprehensive understanding of molecular regulation during disease progression.</p>
2023-07-26 | MTBLS7623 | MetaboLights
Project description:The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality. Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17-1.41), CTSD (1.15-1.37), CD163 (1.09-1.30), IGFBP2 (1.05-1.30), and FABP4 (1.04-1.29)] and ACM and four proteins [GAL4 (1.38-1.56), CTSD (1.14-1.43), CD163 (1.09-1.36), and IGFBP2 (1.03-1.35)] with CVM. Three proteins [GAL4 (1.14-1.57), CTSD (1.12-1.50), and FABP4 (1.05-1.55)] were significantly associated with incident CE and two [GAL4 (1.03-1.54) and CTSD (1.01-1.46)] were associated with incident HF after adjusting for traditional risk factors including N-terminal pro-brain natriuretic peptide. In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.
| S-EPMC7754972 | biostudies-literature
Project description:BackgroundDespite the well-documented association between diabetes and active tuberculosis, evidence of the association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent.MethodsWe included observational studies that applied either the tuberculin skin test or the interferon gamma release assay for diagnosis of LTBI and that provided adjusted effect estimate for the association between diabetes and LTBI. We searched PubMed and EMBASE through 31 January 2016. The risk of bias of included studies was assessed using a quality assessment tool modified from the Newcastle-Ottawa scale.ResultsThirteen studies (1 cohort study and 12 cross-sectional studies) were included, involving 38263 participants. The cohort study revealed an increased but nonsignificant risk of LTBI among diabetics (risk ratio, 4.40; 95% confidence interval [CI], 0.50-38.55). For the cross-sectional studies, the pooled odds ratio from the random-effects model was 1.18 (95% CI, 1.06-1.30), with a small statistical heterogeneity across studies (I2, 3.5%). The risk of bias assessment revealed several methodological issues, but the overall direction of biases would reduce the positive causal association between diabetes and LTBI.ConclusionsDiabetes was associated with a small but statistically significant risk for LTBI. Findings from this review could be used to inform future cost-effectiveness analysis on the impact of LTBI screening programs among diabetics.
| S-EPMC5399944 | biostudies-literature