Introduction
Sleep quality, glucose regulation, and age-related metabolic changes converge on physiological pathways linked to cognitive decline across the lifespan. More than 500 million adults worldwide meet criteria for impaired glucose regulation, highlighting the scale of metabolic vulnerability in aging populations1. Aging is also associated with altered sleep architecture, increased fragmentation, and higher apnea burden, all of which may contribute to metabolic and neurovascular risk2. Yet how sleep architecture (macro and microarchitecture) and sleep-disordered breathing relate to glucose regulation in aging, and whether these relationships differ by sex, remains incompletely understood.
Aims/Objectives
We investigated the relationship between traditional sleep architecture, sleep depth (Odds Ratio Product; ORP), and glucose regulation in community-dwelling middle-aged to older adults. We further examined whether these associations differed by sex.
Methods
The study conformed to the standards set by the Declaration of Helsinki. Eighty-six adults (n=56 women; age 63.8±5.9 years) from the Brain in Motion II study completed overnight in-home Level II polysomnography and fasting blood sampling. Glucose status was classified as normoglycemic (n=45; ≤5.6 mmol/L) or glucose-dysregulated (n=40; >5.6 mmol/L). Groups were comparable for age and sex.
Results
Individuals with glucose dysregulation had higher body mass index (30.8±4.9 vs. 27.3±5.1 kg/m²; p=0.002), higher body fat percentage (38.1±7.1 vs. 35.1±7.2%; p<0.001), and lower V̇O₂max (24.9±5.3 vs. 27.9±4.7 mL/kg/min; p=0.007). Glucose-dysregulated participants displayed higher sleep efficiency (76.5±10.1 vs. 70.2±10.4%; p=0.002), shorter sleep-onset latency (25.3±36.2 vs. 42.6±45.6 min; p=0.037), and less full wakefulness (ORP decile 10: 8.9±6.4 vs. 13.7±7.1% of total sleep time; p=0.002). Total sleep time (346.0±65.0 vs. 327.6±72.8 min; p=0.278) and wake after sleep onset (137.1±58.3 vs. 125.4±51.7 min; p=0.241), did not differ significantly between groups. No group differences were observed in other ORP deciles or NREM stages.
Sex-based analyses showed that females had higher sleep efficiency (75.0±10.4 vs. 69.8±10.9%; p=0.012), less time awake (115.4±52.4 vs. 141.0±60.5 min; p=0.018), and greater NREM stage 3 sleep (55.1±40.1 vs. 17.7±26.6 min; p<0.001) compared with males. Sex-by-glucose interactions indicated that differences in sleep efficiency and wakefulness by glucose status were evident in females but not males.
Overall, apnea–hypopnea index (AHI) did not differ by glucose group or sex; however, glucose-dysregulated females exhibited higher AHI than normoglycemic females (26.1±16.8 vs. 15.7±11.9 events·h⁻¹, p=0.046). When categorized by OSA severity, glucose-dysregulated participants showed a greater burden of moderate-to-severe OSA, whereas normoglycemic participants were more likely to fall within no or mild OSA categories. Hypoxia-related indices were also worse in glucose-dysregulated participants, particularly among females.
Conclusion
Our findings suggest that the relationship between glucose regulation and sleep in older adults is more nuanced than expected. Glucose-dysregulated participants exhibited patterns consistent with increased homeostatic sleep pressure, including higher sleep efficiency and reduced wakefulness, potentially reflecting early physiological adaptations preceding overt sleep disruption. The paradoxically “better” sleep outcomes may be influenced by higher BMI and a greater burden of undiagnosed mild-to-moderate OSA, with chronic sleep fragmentation, REM disruption, and nocturnal hypoxia contributing to compensatory sleep drive. This underscores the importance of considering sleep-disordered breathing when evaluating sleep–glucose interactions and may inform early preventive strategies targeting both metabolic and sleep pathways to support healthy aging.