There are no clinical studies that have investigated the differences in blood serum metabolome between obstructive sleep apnea (OSA) patients and controls. In a single-center prospective observational study, we compared metabolomic profiles in the serum of OSA patients with apnea–hypopnea index (AHI) ≥ 15/h and control individuals. Peripheral blood was obtained at 3 different time points overnight: 9:00 p.m.; 5:00 a.m. and 7:00 a.m. We used a targeted approach for detecting amino acids and biogenic amines and analyzed the data with ranked general linear model for repeated measures. We recruited 31 patients with moderate-to-severe OSA and 32 controls. Significant elevations in median concentrations of alanine, proline and kynurenine in OSA patients compared to controls were detected. Significant changes in the overnight dynamics of serum concentrations occurred in OSA: glutamine, serine, threonine, tryptophan, kynurenine and glycine levels increased, whereas a fall occurred in the same biomarker levels in controls. Phenylalanine and proline levels decreased slightly, compared to a steeper fall in controls. The study indicates that serum profiles of amino acid and biogenic amines are significantly altered in patients with OSA referring to vast pathophysiologic shifts reflected in the systemic metabolism.
There are no clinical studies that have investigated the differences in blood serum metabolome between obstructive sleep apnea (OSA) patients and controls. In a single-center prospective observational study, we compared metabolomic profiles in the peripheral blood of OSA patients with apnea-hypopnea index (AHI) > 15/h and control individuals. Blood was obtained at 3 different time points overnight: 21:00 p.m.; 5:00 a.m. and 7:00 a.m. We used a targeted approach for detecting amino acids and biogenic amines and analyzed the data with ranked general linear model for repeated measures. We recruited 31 patients with moderate-to-severe OSA and 32 controls. Significant elevations in median concentrations of alanine, proline and kynurenine in OSA patients compared to controls were detected. Significant changes in the overnight dynamics of peripheral blood concentrations occurred in OSA: glutamine, serine, threonine, tryptophan, kynurenine and glycine levels increased, whereas a fall occurred in the same biomarker levels in controls. Phenylalanine and proline levels decreased slightly, compared to a steeper fall in controls. The study indicates that serum profiles of amino acid and biogenic amines are significantly altered in patients with OSA referring to vast pathophysiologic shifts reflected in the systemic metabolism.
BackgroundApnoea-hypopnoea index (AHI) forms the basis for severity of obstructive sleep apnoea (OSA), a condition expected to reprogram metabolic pathways in humans. We aimed at identifying the AHI breakpoint from which the majority of significant changes in the systemic metabolome of patients with sleep complaints occur.MethodsIn a prospective observational study on symptomatic individuals, who underwent polysomnography for the diagnosis of OSA, profiles of 187 metabolites including amino acids, biogenic amines, acylcarnitines, lysophasphatidylcholines, phosphatidylcholines and sphingomyelins were analysed with liquid chromatography-mass-spectrometry in peripheral blood drawn at 3 different time points overnight. Comparisons of rank-transformed data with general linear model for repeated measures after dichotomizing the study group at different AHI levels were applied to define the best cut-off based on Cohen's f.ResultsSixty-five subjects were recruited with their median AHI of 15.6 events per hour. The mean Cohen's f over the metabolites was highest (0.161) at an AHI level of 5·h−1representing the metabolomic threshold (MT). Of the particular between-group differences, 8 phosphatidylcholines, 9 acylcarnitines and one amino acid (threonine) had significantly lower concentrations in the individuals with an AHI level equal to or above the MT. The metabolomic changes at AHI levels defining moderate and severe OSA were smaller than at AHI of 5·h−1.ConclusionsThe MT for patients with sleep complaints described in this report for the first time coincides with the AHI threshold required to confirm the diagnosis of OSA.
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