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INTRODUCTION: Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility. OBJECTIVE: The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework. METHODS: We used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure. RESULTS: Only 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P < 0.05) with offspring BMI z-scores at age 2 years in a meta-analytic framework including at least two studies: arabinose (Coefmeta = 0.40 [95% CI 0.10,0.70], Pmeta = 9.7 × 10-3), guanidinoacetate (Coefmeta = - 0.28 [- 0.54, - 0.02], Pmeta = 0.033), 3-ureidopropionate (Coefmeta = 0.22 [0.017,0.41], Pmeta = 0.033), 1-methylhistidine (Coefmeta = - 0.18 [- 0.33, - 0.04], Pmeta = 0.011), serine (Coefmeta = - 0.18 [- 0.36, - 0.01], Pmeta = 0.034), and lysine (Coefmeta = - 0.16 [- 0.32, - 0.01], Pmeta = 0.044). No associations were robust to multiple testing correction. CONCLUSIONS: Despite including three cohorts with large sample sizes (N > 100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.
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Lisina , Metabolómica , Niño , Femenino , Embarazo , Humanos , Preescolar , Índice de Masa Corporal , Reproducibilidad de los Resultados , Modelos LinealesRESUMEN
BACKGROUND: acute myocardial infarction (AMI) is often followed by hyperglycemia. To date, there is no study that examine the role of myocardial damage, ion channel changes and increased inflammatory response as a pathomechanism of malignant arrhythmias due to hyperglycemia in AMI patients. The aim of this study is to determine the effect of acute hyperglycemia on the occurence of malignant arrhythmias, troponin I, VLP, echocardiographic strain, ion channel changes (CaMKII) and hsCRP. This study also aims to assess the effect of troponin I, VLP, GLS, CaMKII and hsCRP on the occurence of malignant arrhythmias in AMI patients with acute hyperglycemia. METHODS: a cross-sectional study followed by a cohort study was conducted on AMI patients treated at ICCU Cipto Mangunkusumo Hospital Jakarta during November 2018 to May 2019 period. Patients with severe infections and who had experienced malignant arrhythmias at admission were excluded from the study. The occurence of malignant arrhythmias as the main outcome of this study and CaMKII level were assessed on the fifth day of treatment. Patients who died before the fifth day of treatment due to causes other than malignant arrhythmias were excluded from analysis. The association between acute hyperglycemia with VLP and the occurence of malignant arrhythmias was analyzed through a chi-square test, whereas the differences between troponin I, GLS, CaMKII and hsCRP, based on the hyperglycemia status of the patient, were analyzed by Mann-Whitney U test. RESULTS: a total of 110 patients were included in the study. Two patients died on the third day of observation due to malignant arrhythmias. No significant relationship was found between acute hyperglycemia in AMI and malignant arrhythmias (RR = 1,38, 95%CI 0.50-3.77). There were differences of CaMKII level on day-1 and day-5 between those who were experienced malignant arrhytmia and those who were not (p-value for differences are 0,03 and 0,01, respectively. In the acute hyperglycemia group, there was difference of CaMKII day-5 levels between positive and negative VLP (p = 0.03). CONCLUSION: it was concluded that the inititial stage of AMI causes more dominant myocardial damage, as compared to metabolic factors. In the next stage of AMI, acute hyperglycemia increases ROS and the activation of ion channel changes described by CaMKII. This change results in electrophysiological remodeling of the heart, as seen in the VLP image on SA-ECG.