Beschreibung:
Background: Advances in metabolomics enable broad exploration of metabolism in cystic fibrosis (CF) and cystic fibrosis‐related diabetes (CFRD).Methods: Plasma from 30 CF adults hospitalized for pulmonary symptoms (15 with CFRD) and 17 healthy controls were analyzed by high‐resolution LC‐MS. Data was analyzed in R using an in‐house pipeline that performs log2‐transformation, quantile normalization, FDR analysis using limma, and hierarchal clustering analysis (HCA). The METLIN Database was used to match ions to known metabolites. A targeted metabolome‐wide association study (MWAS) with serum 25‐hydroxyvitamin D (25(OH)D) levels was also done.Results: Of 11,736 metabolites, 4,522 significantly differed between CF and controls (q = 0.01). HCA revealed 55 distinct metabolomic clusters differentiating CF and control subjects. Derivatives of vitamin D3 and several acylcarnitines were lower in CF. MWAS identified 268 metabolites associated with serum 25(OH)D levels, including octanoylcarnitine (r = 0.51, P = 0.01). A total of 74 metabolites significantly differentiated CF patients ± CFRD (q = 0.05), including coenzyme A and ATP.Conclusions: Plasma metabolomic profiling can distinguish adults with or without CF and CF patients ± CFRD; other metabolites are linked with vitamin D status. These pilot data suggest fatty acid β‐oxidation pathways may be perturbed in certain CF patients.Grant Funding Source: Supported by National Institutes of Health (T32 DK007298‐32S1, K23 AR054334, and K24 RR023356).