OBJECTIVEShort 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 METHODSThis 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.RESULTSIVGTT-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.CONCLUSIONSSleep 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.

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As previously reported [Reid, 1953a], ACTH preparations do not readily enhance the diabetogenic potency (in cats) of purified preparations of growth hormone (GH), in contrast to that of crude ox-pituitary extracts. It is now postulated that crude extracts are rich in a 'co-factor' which enables, or helps, ACTH to enhance the diabetogenic activity of GH. Some evidence has been found for the presence of such a 'co-factor' in crude chorionic gonadotrophin, in semipurified LH, and in crude 'albumin fractions' obtained as by-products in the isolation of GH from crude extracts. It was previously shown that the effectiveness of different ACTH preparations, in enhancing the diabetogenic potency of crude GH preparations, bore little relation to their activity in the Sayers test (ascorbic acid depletion). It now appears that this lack of correlation is not attributable to differences in the rate of absorption after injection into cats. The diabetogenic potency of an alkaline pituitary extract was found to be enhanced when a preparation of ox 'crude corticotropin' (containing some GH), or of pig GH, was given concurrently at an acidic pH so that its intrinsic diabetogenic activity was low. This ' ACTH-like activity' was not found with purified ox GH under these conditions.