Clamping Cortisol and Testosterone Mitigates the Development of Insulin Resistance during Sleep Restriction in Men.
Level 2 - randomized trial
Randomized double-blind crossover trial
PubMed 34043794 · doi:10.1210/clinem/dgab375
What was done
A randomized, double-blind, in-laboratory crossover study evaluated 34 healthy young men subjected to 4 nights of sleep restriction (4 hours/night) under two conditions in random order: a dual hormone clamp (cortisol and testosterone fixed) or matching placebo (cortisol and testosterone not fixed). Fasting blood samples and 23 serial samples during a 3-hour oral glucose tolerance test (OGTT) were collected before and after sleep restriction in each condition. Measured outcomes included cytokines, hormones, and overall insulin sensitivity derived from HOMA-IR, the Matsuda index, and the minimal model.
What was found
Sleep restriction with placebo induced hyperinsulinemia, hyperglycemia, and overall insulin resistance (P < 0.001 for each). Clamping cortisol and testosterone mitigated the development of overall insulin resistance (P = 0.046) and hyperinsulinemia (P = 0.014) by 50%, without preventing hyperglycemia. Interleukin-6, high-sensitivity C-reactive protein, peptide YY, and ghrelin showed no significant change, whereas tumor necrosis factor-α and leptin shifted in directions that would have mitigated insulin resistance under sleep restriction alone.
Why it matters
This trial demonstrates that shifts in cortisol and testosterone account for half of the acute impairment in insulin sensitivity during short-term sleep loss in men. It confirms endocrine dysregulation as a direct mechanistic driver of sleep-restriction-induced metabolic dysfunction.
Limits
The study included only a small cohort (n = 34) of healthy young men, limiting generalizability to women, older adults, or individuals with pre-existing metabolic disorders. The protocol tested acute, short-term sleep restriction (4 nights) rather than chronic sleep loss, and the simultaneous clamping design precluded assessing the independent effects of cortisol versus testosterone.