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.     

The Local Addition of Tenoxicam Reduces the Incidence of Low Back Pain after Lumbar Epidural Anesthesia

Background: Postepidural backache is a common postoperative complaint after lumbar epidural anesthesia. Useful interventions to decrease the incidence of postepidural backache would be helpful.

Methods: We performed a prospective, randomized, double-blind study to compare the effect of local addition of tenoxicam on the incidence of postepidural backache after nonobstetric surgery. One thousand unpremedicated ASA physical status I or II patients scheduled for hemorrhoidectomy were assigned randomly to tenoxicam or control groups. Patients in the control group received 25 ml lidocaine, 2%, with epinephrine 1:200,000 epidurally and 4 ml lidocaine, 1%, for local skin infiltration. Patients in the tenoxicam group received 25 ml lidocaine, 2%, with epinephrine 1:200,000 epidurally and 4 ml lidocaine, 1%, with tenoxicam (2 mg) 1:2,000 for local skin infiltration. Patients were interviewed at 24, 48, and 72 h postoperatively using a standard visual analog scale for evaluation of postepidural backache. A patient was considered to have postepidural backache when the postoperative visual analog scale score was higher than the preoperative score.

Results: The incidence of postepidural backache in patients in the control group for the 3 days were 22.8%, 17.4%, and 9.2%, all of which were significantly more frequent than observed in the patients in the tenoxicam group (6.8%, 4.0%, and 1.2%, P < 0.01). There was a significant association between backache and multiple attempts at epidural needle insertion.     

Sympathetic Nervous System Response to Lidocaine Induced Seizures in Cats

The effect on arterial pressure, EEG, preganglionic sympathetic nervous activity and pulse rate of repeated intravenous administrations of lidocaine (3 mg/kg) was investigated in cats anaesthetized with nitrous oxide. A continuous high voltage, burst-suppression EEG indicating constant seizure activity was found, whereas arterial pressure and sympathetic nervous activity did not change significantly. Although the onset of EEG seizure activity did not change the mean sympathetic activity level, the pattern of firing changed dramatically as every EEG seizure triggered a burst of sympathetic impulses. Barostatic reflexes were active after lidocaine administration unless seizure activity occurred. Thiopental 5 mg/kg given intravenously to cats during continuous lidocaine-induced EEG seizures always abolished the seizure activity without excessive depression of arterial pressure.     

ASO Visual Abstract: Temporizing Wound VAC Dressing Until Final Negative Margins are Achieved Reduces Myxofibrosarcoma Local Recurrence

Annals of Surgical Oncology -     

Propofol Anesthesia Compared to Awake Reduces Infarct Size in Rats

Background: Propofol has not been studied directly in animals subject to cerebral ischemia in the conscious state. Strokes are usually induced in animals while they are anesthetized, making it difficult to eliminate anesthetic interactions as a complicating factor. Therefore, to compare the neuroprotective effects of propofol to the unanesthetized state, experiments were performed using a model that induces a stroke in the conscious rat.

Methods: Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor endothelin. Four days before the strokes were induced, a guide cannula was implanted for the injection of endothelin. On the day of the experiment, endothelin (6.0 pmol in 3 [mu]l) was injected into the striatum. Propofol (25 or 15 mg [middle dot] kg-1 [middle dot] h-1) or intralipid (vehicle) were infused for 4 h starting immediately after the endothelin injection. In another series, the propofol infusion was begun 1 h after the endothelin injection and continued for 4 h. Three days later, the animals were killed, and the brains were sectioned and stained.

Results: The propofol group (25 mg [middle dot] kg-1 [middle dot] h-1) had a significantly reduced infarct size (0.7 +/- 0.21 mm3, first 4 h; 0.27 +/- 0.07 mm3, started 1 h after initiation of infarct) compared with the intralipid controls (3.40 +/- 0.53 mm3). To exclude a direct interaction between propofol and endothelin, in thiobutabarbital anesthetized rats, endothelin-induced cerebral vasoconstriction was examined using videomicroscopy, with or without propofol. Propofol had no effect on the magnitude or time course of the endothelin-induced vasoconstriction.     

全麻复合硬膜外阻滞抑制上腹部手术应激反应

目的：通过检测单纯全麻或全麻加硬膜外阻滞病人的血清皮质醇、胰岛素、血糖浓度及血压变化,比较两种麻醉方法抑制手术时应激反应的差异。方法：将２５例ＡＳＡＩ～Ⅱ级上腹部择期手术病人随机分为两组：Ｇ组按常规方法诱导后行气管内插管全麻,Ｃ组先行硬膜外穿刺注药置管后再行气管内插管全麻。分别在入室、切皮后１０分钟、腹腔探查、缝合腹腊后四个时点记录血流动力学及血清皮质醇、胰岛素、血糖等各项参数。结果：Ｇ组皮质醇在     

Desflurane Reduces the Febrile Response to Administration of Interleukin-2

Background: Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane-induced anesthesia produces a dose-dependent inhibition of the febrile response.

Methods: Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated-measures analysis of variance and Scheffe's F tests.

Results: Values are presented as mean +/- SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/- 2.0 [degree sign]C [center dot] h on the control day to 2.1 +/- 2.3 [degree sign]C [center dot] h during 0.6 MAC and to -1.4 +/- 3.1 [degree sign]C [center dot] h during 1.0 MAC desflurane-induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a dose-dependent fashion: 38.6 +/- 0.5 [degree sign]C on the control day, 37.7 +/- 0.7 [degree sign]C during 0.6 MAC and 37.2 +/- 1.0 [degree sign]C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering.