Objective: Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness.

Research Design and Methods: This twelve-day, inpatient General Clinical Research Center study included twenty healthy men (age 20-35 years, BMI 20-30 kg/m²). Subjects spent 10 hours/night in bed for ≥8 nights including 3 inpatient nights (sleep-replete condition), followed by 5 hours/night of time in bed for 7 nights (sleep-restricted condition). Subjects received modafinil (300 mg/day) or placebo during sleep restriction. Diet and activity were controlled. On the last two days of each condition we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic hyperinsulinemic clamp. Salivary cortisol, 24-hr urinary catecholamines, and neurobehavioral performance were measured.

Results: IVGTT-derived insulin sensitivity was reduced 20 ± 24% (mean±SD) after sleep restriction (p=0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced 11±5.5% (p< 0.04) after sleep restriction. Glucose tolerance and the Disposition Index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51±8% with sleep restriction, p<0.02), urinary catecholamines or slow wave sleep.

Conclusion: Sleep restriction (5 hrs/night) for one week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance.