The association of objective daytime sleepiness with impaired glucose metabolism in patients with obstructive sleep apnea: a multi-omics study

Study Objectives: To examine the joint effect of obstructive sleep apnea (OSA) and objective excessive daytime sleepiness (EDS) on glucose metabolism and the underlying mechanisms. Methods: We included 127 patients with OSA. The multiple sleep latency test (MSLT) and Epworth sleepiness scale (ESS) were used to assess objective and subjective EDS, respectively. Disordered glucose metabolism was defined as either a physician diagnosis or having fasting blood glucose levels >= 5.6 mmol/L. Values of fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) higher than the median values of our sample were defined as high fasting insulin and insulin resistance. Serum metabolomics and fecal microbiota were used to explore underlying mechanisms. Results: Lower MSLT values were associated with higher levels of fasting blood glucose, fasting insulin, and HOMA-IR. Furthermore, objective EDS was associated with increased odds of disordered glucose metabolism, elevated fasting insulin, and insulin resistance. Dysregulation of serum valine degradation and dysbiosis of fecal Bacteroides thetaiotaomicron were associated with impaired glucose metabolism in OSA with objective EDS. No association between subjective EDS and impaired glucose metabolism was observed. Conclusions: OSA with objective, but not subjective, EDS is associated with an increased risk of disordered glucose metabolism and insulin resistance. Dysregulation of valine degradation and dysbiosis of B. thetaiotaomicron appear to link objective EDS and disordered glucose metabolism in OSA.