Respiratory medicine · 2025
Assessment of the metabolome across the glucose tolerance spectrum in adults with cystic fibrosis hospitalized for pulmonary exacerbations.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Yang Chin-An, Batross Jonathon, Gonzalez Ramirez Lucia A, Chandler Joshua, Walker Douglas, Tran ViLinh, Jones Dean P, Olveira Gabriel, Ziegler Thomas R, Tangpricha Vin, Alvarez Jessica A
Аннотация
BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is one of the most common co-morbidities among adults with cystic fibrosis (CF), yet the mechanisms determining its development remain unclear. This study explored the underlying biological mechanisms associated with CFRD development using plasma high-resolution metabolomics (HRM).
METHODS: This cross-sectional study included 52 adults with CF hospitalized for a pulmonary exacerbation. Participants were categorized into three glucose tolerance groups: normal glucose tolerance (n = 26), pre-diabetes (n = 9), and CFRD (n = 17), based on data abstraction from the electronic medical record. Untargeted metabolomics were performed on fasted plasma using dual column liquid chromatography and high-resolution mass spectrometry. Analysis of covariates and pathway enrichment analysis were used to define the metabolites and pathways that differentiated between glucose tolerance groups. A sub-set analysis was performed using highest confidence metabolites quantified by reference standardization.
RESULTS: Among the 2134 features in HILIC and 1909 in C18 modes, glucose tolerance status was significantly associated with 94 and 107 features (p < 0.05), which were significantly enriched within three and eleven pathways, respectively. These pathways included redox-related processes, such as glutathione metabolism and the tricarboxylic acid cycle, as well as pentose phosphate pathway. In the sub-set analysis, two per- and polyfluoroalkyl substances were identified as decreasing with worsening glucose intolerance group (FDR q = 0.07 and 0.11, respectively).
DISCUSSION: Untargeted metabolomics demonstrated several redox-related pathways differentiating between glucose tolerance categories among adults with CF during a pulmonary exacerbation. Future targeted research is warranted to determine biological mechanisms of CFRD pathophysiology, including the role of the environment.
METHODS: This cross-sectional study included 52 adults with CF hospitalized for a pulmonary exacerbation. Participants were categorized into three glucose tolerance groups: normal glucose tolerance (n = 26), pre-diabetes (n = 9), and CFRD (n = 17), based on data abstraction from the electronic medical record. Untargeted metabolomics were performed on fasted plasma using dual column liquid chromatography and high-resolution mass spectrometry. Analysis of covariates and pathway enrichment analysis were used to define the metabolites and pathways that differentiated between glucose tolerance groups. A sub-set analysis was performed using highest confidence metabolites quantified by reference standardization.
RESULTS: Among the 2134 features in HILIC and 1909 in C18 modes, glucose tolerance status was significantly associated with 94 and 107 features (p < 0.05), which were significantly enriched within three and eleven pathways, respectively. These pathways included redox-related processes, such as glutathione metabolism and the tricarboxylic acid cycle, as well as pentose phosphate pathway. In the sub-set analysis, two per- and polyfluoroalkyl substances were identified as decreasing with worsening glucose intolerance group (FDR q = 0.07 and 0.11, respectively).
DISCUSSION: Untargeted metabolomics demonstrated several redox-related pathways differentiating between glucose tolerance categories among adults with CF during a pulmonary exacerbation. Future targeted research is warranted to determine biological mechanisms of CFRD pathophysiology, including the role of the environment.