Recently, there was an abundance of studies being conducted on the metabolomic profiling of tuberculosis patients. Amino acids are critical metabolites for the immune system, as they might contribute to providing nutrients for the host intracellular pathway. In tuberculosis, several amino acids play important roles in both the mycobacteria infection mechanism and the host. Individual studies showed how the dynamics of metabolite products that result from interactions between Mycobacterium tuberculosis (Mtb) and the host play important roles in different stages of infection. In this review, we focus on the dynamics of amino-acid metabolism and identify the prominent roles of amino acids in the diagnostics and treatment of tuberculosis infection. Online resources, including PubMed, ScienceDirect, Scopus, and Clinical Key, were used to search for articles with combination keywords of amino acids and TB. The inclusion criteria were full-text articles in English published in the last 10 years. Most amino acids were decreased in patients with active TB compared with those with latent TB and healthy controls. However, some amino acids, including leucine, isoleucine, valine, phenylalanine, aspartate, and glutamate, were found to be at higher levels in TB patients. Additionally, the biomarkers of Mtb infection included the ratios of kynurenine to tryptophan, phenylalanine to histidine, and citrulline to arginine. Most amino acids were present at different levels in different stages of infection and disease progression. The search for additional roles played by those metabolomic biomarkers in each stage of infection might facilitate diagnostic tools for staging TB infection.

Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children. We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-β, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5–80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts. There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1–3.21)), fasting insulin HR 1.89 (95% CI 1.11–3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62–1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses. The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches. 10.13039/501100001659 German Research Foundation (DFG)—through SFB 1052, project number 209933838, subproject C5; 10.13039/501100002347 Federal Ministry of Education and Research , Germany; European Union– 10.13039/501100008530 European Regional Development Fund ; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03.

Background: It is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study. Methods: We used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λ_R) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h²), shared environment, and genetic correlation (r_g) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age², and sex. Results: Individuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λ_FDR of 1.23 (95% CI 1.20–1.25) for hypertension to λ_FDR of 2.48 (95% CI 2.15–2.86) for T2D. Most of these were higher than in spouses (λ_Spouses < λ_FDR), except for obesity which was slightly higher in spouses. We found moderate heritability for cardiometabolic traits (from h²_CRP: 0.26 to h²_HDL: 0.50). Cardiometabolic disorders showed positive familial co-aggregation, particularly between T2D, MetS, and obesity (from λ_{FDR obesity-MetS}: 1.28 (95% CI 1.24–1.32) to λ_{FDR MetS-T2D}: 1.61 (95% CI 1.52–1.70)), consistent with the genetic correlations between continuous intermediate traits (ranging from r_{g HDL-Triglycerides}: − 0.53 to r_{g LDL-Apolipoprotein B}: 0.94). Conclusions: There is positive familial (co-)aggregation of cardiometabolic disorder, moderate heritability of intermediate traits, and moderate genetic correlations between traits. These results indicate that shared genetics and common genetic architecture contribute to cardiometabolic disease.

Background: Thalassemia carrier screening is a major preventive measure potentially influenced by the level of knowledge, particularly in adolescents. Therefore, this study aimed to analyze the effect of health education on knowledge of thalassemia in adolescents and its association with their willingness to do thalassemia screening.Methods: A cross-sectional study was conducted using data regarding knowledge of thalassemia before and after health education sessions from 229 students at Public Senior High-School 3 Bandung. All participants attended a one-day health education in July 2019. A questionnaire was filled in to measure their knowledge regarding thalassemia before and after the session, including knowledge on etiology and definition, risk of disease, clinical manifestations, treatment, complication, prognosis, and disease prevention. Only data with complete questionnaire responses were included. These responses were scored quantitatively and analyzed for their association with participants’ willingness to screen. Results: Participants were knowledgeable concerning thalassemia before the health education session (median, range: 60.0, 25.0-90.0), and knowledge was increased significantly after the education session (median, range: 80.0, 35.0-100.0) with an increased median difference=19.99 (p-value 0.05), the willingness was slightly associated with improved knowledge regarding the risk of disease (OR: 1.02; 95%CI: 1.00-1.03; p-value <0.005). Conclusion: Health education regarding thalassemia significantly increases general knowledge of thalassemia. However, improving knowledge is not significant in influencing adolescents’ motivation to take the screening tests.

Aims: Type 2 diabetes (T2D) is a global health burden, more prevalent among individuals with attention deficit hyperactivity disorder (ADHD) compared to the general population. To extend the knowledge base on how ADHD links to T2D, this study aimed to estimate causal effects of ADHD on T2D and to explore mediating pathways. Methods: We applied a two-step, two-sample Mendelian randomization (MR) design, using single nucleotide polymorphisms to genetically predict ADHD and a range of potential mediators. First, a wide range of univariable MR methods was used to investigate associations between genetically predicted ADHD and T2D, and between ADHD and the purported mediators: body mass index (BMI), childhood obesity, childhood BMI, sedentary behaviour (daily hours of TV watching), blood pressure (systolic blood pressure, diastolic blood pressure), C-reactive protein and educational attainment (EA). A mixture-of-experts method was then applied to select the MR method most likely to return a reliable estimate. We used estimates derived from multivariable MR to estimate indirect effects of ADHD on T2D through mediators. Results: Genetically predicted ADHD liability associated with 10% higher odds of T2D (OR: 1.10; 95% CI: 1.02, 1.18). From nine purported mediators studied, three showed significant individual mediation effects: EA (39.44% mediation; 95% CI: 29.00%, 49.73%), BMI (44.23% mediation; 95% CI: 34.34%, 52.03%) and TV watching (44.10% mediation; 95% CI: 30.76%, 57.80%). The combination of BMI and EA explained the largest mediating effect (53.31%, 95% CI: −1.99%, 110.38%) of the ADHD–T2D association. Conclusions: These findings suggest a potentially causal, positive relationship between ADHD liability and T2D, with mediation through higher BMI, more TV watching and lower EA. Intervention on these factors may thus have beneficial effects on T2D risk in individuals with ADHD.

Purpose: This study aims to provide new insights into the potential of oyster mushroom (Pleurotus ostreatus) ethanolic extract in preventing obesity through the inhibition of Pparg expression and modulation of methylation level on Pparg promoter during 3T3-L1 adipocyte differentiation. Methods: This in vitro quantitative experimental study was conducted by treating the 3T3-L1 cell line differentiated using 0.5 mM methyl-isobutyl-xanthine, 1 μM dexamethasone, and 10 μg/mL insulin-containing medium with oyster mushroom ethanolic extract. The extract was obtained from 80 g of dried oyster mushroom powder extracted three times with 800 mL of ethanol, filtered, evaporated, and reconstituted in dimethyl sulfoxide (DMSO) to final concentrations of 0, 25, 50, and 100 μg/mL, with DMSO limited to 0.5% in all solutions. Pparg mRNA expression was quantified by qRT-PCR analysis and Pparg promoter methylation levels were measured quantitatively by pyrosequencing of bisulfite-treated DNA samples. Results: The addition of 25 μg/mL oyster mushroom ethanolic extract significantly suppressed Pparg mRNA expression with no significant change in the Pparg promoter methylation levels. Conclusion: Oyster mushroom ethanolic extract inhibited Pparg mRNA expression without altering Pparg promoter methylation, suggesting reduced adipocyte differentiation. This study emphasizes the potential of oyster mushroom in the prevention or treatment of obesity by inhibiting adipocyte differentiation.