Evaluation of Sex Differences in Glucose Metabolism in Response to Sleep Curtailment

Two-thirds of Americans report regularly obtaining an insufficient amount of sleep. Chronic sleep deficiency is associated with negative health consequences such as obesity, cardiovascular disease, diabetes, and metabolic syndrome. Laboratory studies have shown that sleep restriction reduces glucose tolerance in otherwise healthy adults, and it is now well established that sleep restriction decreases insulin sensitivity. However, there is a significant gap in the literature regarding how sex differences may drive disparate metabolic outcomes in men and women in response to sleep loss.

Epidemiological studies strongly suggest that women and men may respond differently to the physiological challenges associated with sleep restriction and circadian disruption. Trouble sleeping is more prevalent in women compared to men, and sleep disturbances appear to be associated with higher risk of obesity, hypertension, and elevated HbA1c in women compared to men. Although multiple causative mechanisms have been explored, most laboratory studies investigating the mechanisms by which sleep disturbances impair metabolism have been conducted solely in men or have not been powered for sex differences.

One potential mechanism underlying sex differences in glucose regulation after sleep loss is the glucagon-like peptide-1 (GLP-1) pathway. GLP-1 reduces blood glucose by stimulating insulin secretion and inhibiting glucagon secretion in response to food intake and is the target of promising new treatments for insulin resistance and obesity such as Ozempic and Wegovy. Interestingly, women exhibit a greater response to treatment with these GLP-1 receptor agonist drugs; additionally, one laboratory study found decreased GLP-1 levels in women but not in men after 4 days of sleep curtailment.

This study will use a randomized crossover design in young men and premenopausal women to test the hypotheses that sleep loss impairs glucose tolerance more in women than in men, and that this difference is partially mediated by sex-dependent responses in GLP-1 after sleep curtailment.

Currently, there are no sex-specific recommendations for management of diabetes or sleep loss, despite evidence that women may bear a greater disease burden than men. Understanding sex differences in glucose metabolism in response to sleep curtailment is critical for making more effective and individualized treatment recommendations to mitigate the adverse metabolic effects of sleep restriction in women and men.