Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men

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 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20–35 years and BMI 20–30 kg/m²). Subjects spent 10 h/night in bed for ≥8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured.

RESULTS

IVGTT-derived insulin sensitivity was reduced by (means ± SD) 20 ± 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 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.

CONCLUSIONS

Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance.The average sleep duration in the U.S. has fallen below 7 h per night, a drop of ∼2 h per night over the last century and >1 h per night over the last 40 years (1,2). Cross-sectional and longitudinal studies have demonstrated a link between short sleep duration or poor sleep quality and increased risk of obesity (3–7), diabetes (7–11), hypertension (12), cardiovascular disease (13,14), the metabolic syndrome (15), and early mortality (14,16–21). Short-term sleep restriction (4 h/night for 1 week in a laboratory setting) impaired glucose tolerance during a frequently sampled intravenous glucose tolerance test (IVGTT) in healthy subjects (22).In healthy subjects, the mechanisms leading to impaired glucose tolerance with short-term reductions in nightly sleep duration are unclear. Decreases in insulin secretion have been implicated, and sleep restriction increases cortisol levels, which could influence glucose tolerance (22). Further, insulin resistance has been reported in two very different models of disrupted sleep: sleep apnea (23) and experimental disruption of slow-wave sleep (24). In the latter model, the extent of slow-wave sleep disruption predicted reductions in insulin sensitivity (24).Our primary goal was to test the hypothesis that sleep restriction in healthy subjects reduces insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp. Insulin secretion was assessed using IVGTTs. To identify possible mechanisms by which sleep restriction may affect insulin sensitivity, we assessed the relationships between changes in insulin sensitivity and changes in cortisol, catecholamines, and slow-wave sleep. Further, we tested the ability of modafinil to ameliorate the adverse effects of sleep restriction on insulin sensitivity. Modafanil activates central, wake-promoting dopaminergic and noradrenergic mechanisms (25,26) and ameliorates the adverse effects of sleep deprivation on alertness and performance (27–29)—impairments that have been attributed to reduced brain glucose utilization (30). Thus, we performed hyperinsulinemic-euglycemic clamps and intravenous glucose tolerance twice: at baseline in sleep-replete individuals and after 7 nights of sleep restriction (5 h in bed) in healthy individuals randomized to daily treatment with placebo or modafinil.