Autonomic imbalance mediates sleep apnea-specific hypoxic burden and glucose metabolism in obstructive sleep apnea: A large-scale observational study.

OBJECTIVE

Obstructive sleep apnea (OSA) is associated with autonomic imbalance and glucose metabolism disorders. However, whether autonomic imbalance mediates the association between sleep apnea-specific hypoxic burden (SASHB) and glucose metabolism disorders was also unknown.

METHODS

We enrolled 2470 suspected OSA patients between January 2021 and May 2025, who underwent polysomnography, biochemical testing, and heart rate variability (HRV) assessment. Logistic regression was performed to estimate odds ratios for glucose metabolism disorders across quartiles of both SASHB and HRV indices. Mediation analysis examined five classic HRV indices (Mean R-R intervals; SDNN index; Centroid of R-R distribution; Approximate Entropy; LF/HF) as autonomic imbalance markers.

RESULTS

Compared with the lowest quartile, higher SASHB levels were significantly associated with increased risks of hyperglycemia (ORs: 1.161, 1.021, and 1.653; P < 0.001), hyperinsulinemia (ORs: 1.455, 1.725, and 2.459; P < 0.001), and insulin resistance (ORs: 1.431, 1.733, and 2.381; P < 0.001). Conversely, higher AppEn levels were associated with decreased risks of hyperglycemia (ORs: 0.799, 0.680, and 0.825; P = 0.043), hyperinsulinemia (ORs: 0.865, 0.771, and 0.538; P < 0.001), and insulin resistance (ORs: 0.794, 0.694, and 0.598; P < 0.001). Mediation analysis revealed that HRV indices exerted partial mediating effects, with indirect effect (OR) values of 1.044, 1.042, and 1.043 for the three outcomes, respectively.

CONCLUSIONS

The study results indicate that SASHB is associated with glucose metabolism disorders, and autonomic imbalance may play a mediating role in such an association. These findings suggest that targeting autonomic imbalance might be a promising therapeutic strategy for OSA-related glucose metabolism disorders.