Metabolomics Analysis Reveals Molecular Signatures of Metabolic Complexity in Children with Hypercholesterolemia.

Despite the importance of hypercholesterolemia in children, it is overlooked, and there are currently few metabolomics-based approaches available to understand its molecular mechanisms. Children from a birth cohort had their cholesterol levels measured with the aim of identifying the metabolites for the molecular biological pathways of childhood hypercholesterolemia. One hundred and twenty-five children were enrolled and stratified into three groups according to cholesterol levels (acceptable, <170 mg/dL, n = 42; borderline, 170-200 mg/dL, n = 52; and high, >200 mg/dL, n = 31). Plasma metabolomic profiles were obtained by using 1H-nuclear magnetic resonance (NMR) spectroscopy, and partial least squares-discriminant analysis (PLS-DA) was applied using the MetaboAnalyst 5.0 platform. Metabolites significantly associated with different cholesterol statuses were identified, and random forest classifier models were used to rank the importance of these metabolites. Their associations with serum lipid profile and functional metabolic pathways related to hypercholesterolemia were also assessed. Cholesterol level was significantly positively correlated with LDL-C and Apo-B level, as well as HDL-C and Apo-A1 level separately, whereas HDL-C was negatively correlated with triglyceride level (p < 0.01). Eight metabolites including tyrosine, glutamic acid, ornithine, lysine, alanine, creatinine, oxoglutaric acid, and creatine were significantly associated with the different statuses of cholesterol level. Among them, glutamic acid and tyrosine had the highest importance for different cholesterol statuses using random forest regression models. Carbohydrate and amino acid metabolisms were significantly associated with different cholesterol statuses, with glutamic acid being involved in all amino acid metabolic pathways (FDR-adjusted p < 0.01). Hypercholesterolemia is a significant health concern among children, with up to 25% having high cholesterol levels. Glutamic acid and tyrosine are crucial amino acids in lipid metabolism, with glutamic-acid-related amino acid metabolism playing a significant role in regulating cholesterol levels.

Retinal Thickness Associates with Cognition Dysfunction in Young Adult with Type 1 Diabetes in Taiwan.

Background: Several factors could affect the cognitive dysfunction in patients with type 1 diabetes (T1D). Objectives: To report the characteristic of cognitive dysfunction in T1D and find its association with the retinal thickness. Subjects: We recruited one hundred and seven patients with T1D in our study. Methods: Detailed clinical and demographic factors and Cambridge Automated Neuropsychological Test Battery (CANTAB) were performed in all participants. The age at onset>5 years old and ≤5 years old groups was defined as old- and young-onset groups. The levels of the average values of 5-year glycated hemoglobin (HbA1c_5) before study were collected. Ophthalmic study and central retinal thickness (CRT) were performed. Results: The median age of T1D was 24.9 years old and 57 participants were women. The median age at onset was 7.4 years old, and mean disease duration was 17.2 years. After adjusting off multiple covariates by the regression analyses, the young-onset group had significantly a longer latency in sustained attention than old-onset group (P = 0.02). The HbA1c_5 showed a significantly negative association with the sustained attention (P = 0.03). The average values of CRT showed significantly negative correlations with the reaction time in sustained attention and visual searching (P = 0.04 and P < 0.01, respectively). Conclusions: Our results suggest that age at onset and glycemic control had significant impacts on different cognitive domains in T1D. The CRT had a significant correlation with sustained attention, which could be a surrogate markers of brain structural changes in T1D.