Differential regulation of human blood glucose level by interleukin-2 and -6.

While the acute phase reaction to infection is associated with hyperglycemia, during progressing infection hypoglycemia can develop. The cytokines regulating the dynamics of host defense may concurrently contribute to blood glucose regulation. To examine this hypothesis, changes in blood glucose concentrations in healthy men were compared following administration of interleukin-2 (IL-2) and IL-6 representing, respectively, major mediators of the adaptive and the early innate immune response to bacterial infection. Doses of 10 000 IU/kg IL-2 and 0.5 microg/kg IL-6 (vs. placebo) were administered subcutaneously in two groups of men (n = 18 and 16) at 1900 h before a period of nocturnal rest allowing an assessment of changes under basal conditions. Serum concentrations of glucose and of various hormones were assessed every 60 min. Despite generally lowered glucose concentration at night, IL-2 induced a transient but distinct decrease in blood glucose concentration most consistent 8 - 9 hours following injection (p < 0.01). The hypoglycemic response to IL-2 was not accompanied by changes in serum insulin, C-peptide or cortisol. In contrast to IL-2, IL-6 led to an increase in cortisol, followed by a pronounced increase in blood glucose again peaking about 8 hours after injection (p < 0.001). Results indicate a differential regulation of blood glucose concentration by cytokines. Contrasting with the hyperglycemic effects of the acute phase regulator IL-6, the T-cell cytokine IL-2 seems to support glucose uptake and utilization by immune cells.

Heart rate variability during waking and sleep in healthy males and females.

STUDY OBJECTIVES: The study goal was to investigate autonomic activity with heart rate variability analysis during different sleep stages in males and females. DESIGN: The study utilized a 2 Groups (males, females) x 4 States (waking, stage 2 sleep, stage 4 sleep, rapid-eye movement sleep) mixed design with one repeated, within-subjects factor (i.e., state). SETTING: The study was carried out in the sleep laboratory of the Thomas N. Lynn Institute for Healthcare Research. PARTICIPANTS: Twenty-four healthy adults (fourteen females and ten males). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: All participants underwent polysomnographic monitoring and electrocardiogram recordings during pre-sleep waking and one night of sleep. Fifteen-minute segments of beat-to-beat heart rate intervals during waking, stage 2 sleep, stage 4 sleep, and REM sleep were subjected to spectral analysis. Compared to NREM sleep, REM sleep was associated with decreased high frequency (HF) band power, and significantly increased low frequency (LF) to (HF) ratio. Compared to females, males showed significantly elevated LF/HF ratio during REM sleep. Males also demonstrated significantly decreased HF band power during waking when compared to females. No significant sleep- or gender-related changes in LF band power were found. CONCLUSIONS: The results confirmed changes in autonomic activity from waking to sleep, with marked differences between NREM and REM sleep. These changes were primarily due to stage-related alterations in vagal tone. REM sleep was characterized by increased sympathetic dominance, secondary to vagal withdrawal. The data also suggested gender differences in autonomic functioning during waking and sleep, with decreased vagal tone during waking and increased sympathetic dominance during REM sleep in the males.

Disruption of normal gastric myoelectric functioning by sleep.

STUDY OBJECTIVES: The aim of this study was to assess the effects of sleep on gastric myoelectric activity as measured by electrogastrography in healthy individuals. The goal was to elucidate the role of central influences in the regulation of normal gastric functioning. DESIGN: Electrograstrogram (EGG) was recorded during polysomnographically monitored waking and sleep. SETTING: Sleep laboratory. PARTICIPANTS: 17 healthy volunteers. MEASUREMENTS AND RESULTS: EGG parameters were computed for 20-minute segments of pre-sleep waking, stage 2 sleep, stage 4 sleep, and REM sleep using both overall and running spectral analysis of EGG data. The dominant power decreased significantly from waking (31.4 +/- 1.4 dB) to all sleep stages (23.1 +/- 1.5 dB during stage 2; 24.7 +/- 1.4 dB during stage 4; 24.3 +/- 1.3 dB during REM sleep). The percentage of 2-4cpm activity decreased significantly during NREM sleep (64.6 +/- 7.6% during stage 2 sleep; 57.5 +/- 5.5% during stage 4 sleep) compared to its waking value (90.8 +/- 3.2%), but not compared to REM sleep (74.1 +/- 5.4%). The instability coefficient of the dominant frequency increased significantly from waking (0.19 +/- 0.03) to all sleep stages (0.36 +/- 0.05 during stage 2 sleep; 0.47 +/- 0.05 during stage 4; 0.34 +/- 0.05 during REM sleep). No significant differences between the sleep stages were found for any measure. CONCLUSIONS: Sleep is associated with increases in gastric dysrhythmia and instability of the gastric slow wave frequency when compared to waking. These findings suggest that the intrinsic electrical activity of the stomach is significantly influenced by central nervous system mechanisms, and support the notion of a brain-gut axis.

Sleep-related gastro-oesophageal reflux: provocation with a late evening meal and treatment with acid suppression.

BACKGROUND: Two studies were carried out in order to investigate the issue of meal-provoked nocturnal gastrooesophageal reflux. METHODS: In Experiment 1, 20 symptomatic reflux patients underwent both pH and polysomnographic monitoring on two nights. On one night, patients ate a non-provocative meal prior to 19.00 hours, while on the other night patients consumed a late evening meal (21.00 hours). In Experiment 2.17 symptomatic reflux patients were studied using pH and polysomnographic monitoring on two nights subsequent to a late evening provocative meal. On one night, patients received 75 mg of the H2-antagonist ranitidine, while on another night they received a placebo. The data from 12 of the 17 patients studied were used in the analysis. RESULTS: For Experiment 1, no significant differences in the number or duration of reflux events, acid exposure (total %), or polysomnographic measures of per cent of sleep stages between the two nights were observed. The results of the second experiment demonstrated that when given ranitidine, patients experienced significant decrease in acid contact time (total %), and mean duration of reflux events. Subjective reports of discomfort and sleep disturbance were also significantly improved on the drug night. However, significant differences in polysomnographic measures were not observed. CONCLUSIONS: Based on these results, we conclude that in some symptomatic reflux patients a late-night non-provocative meal may not increase the incidence of gastro-oesophageal reflux, and that a low dose of an H2-antagonist is effective in decreasing oesophageal acid contact time following a late evening provocative meal.

The efficacy of omeprazole twice daily with supplemental H2 blockade at bedtime in the suppression of nocturnal oesophageal and gastric acidity.

BACKGROUND: It has been presumed that nocturnal acid breakthrough may pose a risk for the development of nocturnal gastro-oesophageal reflux. AIM: To investigate the occurrence of gastro-oesophageal reflux and acid breakthrough during polygraphically monitored sleep under conditions of powerful acid suppression with omeprazole 20 mg b.d. and an additional dose of ranitidine at bedtime. METHODS: Nineteen individuals with symptomatic gastro-oesophageal reflux disease were studied. Each individual was studied on two occasions subsequent to 1 week of 20 mg of omeprazole treatment b.d. Subjects underwent 24-h oesophageal and gastric pH recording, with polysomnographic monitoring. Participants received either 150 mg ranitidine at bedtime or placebo, prior to a provocative meal. RESULTS: Ranitidine administration resulted in a significant (P < 0.01) reduction in the percentage of time the intragastric pH < 4.0. There was no significant difference with regard to measures of gastro-oesophageal reflux, and reflux events were not noted to occur with a significantly greater frequency during periods of nocturnal acid breakthrough compared with control intervals without acid breakthrough. CONCLUSIONS: The administration of 150 mg ranitidine at bedtime did not significantly alter the occurrence of sleep-related gastro-oesophageal reflux.

Meal composition and its effect on postprandial sleepiness.

Drowsiness is a commonly experienced phenomenon following food ingestion. The present two experiments were designed to assess separately the effects of a solid meal compared to a liquid meal and to an equal volume of water, and the effects of meal constituents (high-fat, high-carbohydrate, or mixed meal) on objective postprandial sleep latencies. Ten normal male subjects participated in each study. Both studies used identical protocols, differing only in the meals the subjects were fed. All subjects underwent a pre-meal baseline nap at 1600 hours. At 1700 hours, subjects consumed a test meal. Naps followed at 1730, 1800, 1900, and 2000 hours. Sleep onset latency was determined by standard polysomnographic measures. In both studies, a one-way repeated-measures ANOVA procedure revealed no significant difference in sleep latencies among the meal conditions for the nap at 1600 hours. However, for the postprandial naps at 1730, 1800, and 2000 hours, the solid meal demonstrated a significant decrease in postprandial sleep latency compared with an equivalent volume of water (control). No significant differences in sleep latency were found between the food constituents. Results indicate that in contrast to a liquid meal, a solid meal produces a decrease in sleep onset latency when compared to an equivalent volume of water. Further, it was demonstrated that meal constituents have no effect on postprandial sleepiness.

A comparison of feeding to cephalic stimulation on postprandial sleepiness.

This study investigated the effects of ingestion of a meal compared to a sham feeding on objectively measured sleepiness. It was hypothesized that the ingestion of a solid meal would produce significantly greater postprandial sleepiness evidenced by shorter sleep onset latencies (SOL) when compared to a sham feeding. Eleven men and eight women without evidence of gastrointestinal disease or sleep disorders participated in the 2-day study. Subjects underwent a premeal baseline nap at 1600 hours and were given a standardized meal at 1700 hours. On one study day, subjects consumed the entire meal, whereas on another study day, they were asked to chew and then expectorate the meal. Naps with polysomnographic monitoring followed at 1730, 1800, and 1900 hours. Sleep onset latencies were determined by standard polysomnographic measures. Statistical analyses revealed the sleep onset latencies for the two meal conditions differed significantly at the 1800 hours postprandial nap only. Individuals demonstrated a transient decrease in sleep latency after consuming a meal compared to a sham feeding. These results lend support to the existence of a gastrointestinal effect on postprandial sleepiness.

Autonomic regulation of cardiac function during sleep in patients with irritable bowel syndrome.

OBJECTIVE: Several studies have provided evidence of abnormal autonomic activity in irritable bowel syndrome (IBS), suggesting that abnormal central nervous system-autonomic nervous system arousal mechanisms may be part of its pathophysiology. The goal was to investigate cardiac sympatho-vagal balance during waking and the different stages of sleep using heart rate variability analysis in IBS patients compared to healthy controls. METHODS: A total of 15 IBS patients (13 female, two male, mean age 34.9 +/- 2.1 yr) and 15 controls (13 female, two male, mean age 36.2 +/- 2.3 yr) were studied during 1 h of pre-sleep quiet waking and during seven-hours of sleep. Polysomnography was used for the determination of state of consciousness. Electrocardiography provided the beat-to-beat intervals, which were then subjected to spectral analysis for determination of the percentage of energy in the low and high frequency bands, respectively. The low frequency/high frequency band ratio was also calculated. For each subject, heart rate variability analysis was performed using 15-min segments of waking, non-rapid eye movement sleep, and rapid eye movement sleep. RESULTS: The low frequency band power was significantly greater in IBS patients during waking. No group differences were found in high frequency band power during any state. The low frequency to high frequency band ratio was significantly greater in IBS patients during rapid eye movement sleep. CONCLUSIONS: IBS patients have greater sympathetic activity during waking and greater overall sympathetic dominance during rapid eye movement sleep. These results support the presence of autonomic abnormalities in patients with IBS. The possibility is discussed that sympathetic dominance during rapid eye movement sleep may play a role in sensitizing the gut to waking stimulation.

Subjective and objective sleep quality in irritable bowel syndrome.

OBJECTIVE: The aim of this study was to compare subjective and objective measures of sleep quality in patients with irritable bowel syndrome (IBS) and controls. METHODS: The Pittsburgh Sleep Quality Index (PSQI) was used to measure subjective sleep quality, and polysomnography was performed during one night to obtain objective measures of sleep quality, including sleep efficiency, sleep latency, number of arousals, and percentage of slow-wave sleep. Participants were 15 IBS patients and 15 healthy controls. RESULTS: The results showed a significantly increased global PSQI score in patients, as well as significantly higher scores on several subcomponents of the PSQI (i.e., sleep quality, sleep latency, habitual sleep efficiency, and daytime dysfunction). Analysis of polysomnographic parameters revealed no significant group differences on any measure. CONCLUSIONS: Complaints of poor sleep quality in the absence of objective sleep abnormalities suggest altered sleep perception, and support that IBS involves exaggerated responses to normal internal or external stimuli.

Using single-subject methodology to investigate psychiatric treatments in systemic lupus erythematosus.

Psychiatric problems are frequently experienced by persons with systemic lupus erythematosus (SLE). Some researchers and clinicians presume that these psychiatric problems are a direct manifestation of the disease, while others suggest that psychosocial and environmental factors have greater etiological significance. Our lack of knowledge regarding the etiology of psychiatric problems in this population is a serious limitation to selecting treatment approaches or to understanding treatment efficacy. Studies that employ group research designs to investigate the etiology or treatment of psychiatric problems in patients with SLE are inherently limited. Therefore, this article provides a general introduction to single-subject methodology and illustrates some potential applications to investigating psychiatric treatments in persons with SLE.

Proximal migration of esophageal acid perfusions during waking and sleep.

OBJECTIVE: Proximal acid migration resulting from gastroesophageal reflux has been implicated in aerodigestive complaints and disorders. This study was designed to investigate the effects of acid volume, posture, and sleep on proximal esophageal acid migration (drop in pH to <4.0). METHODS: The study was performed in 15 healthy adults. A distal esophageal acid perfusion technique to simulate gastroesophageal reflux was used. Esophageal acid perfusions of 1 ml and 3 ml were accomplished at a site 5 cm above the proximal border of the lower esophageal sphincter in the upright and supine positions during waking, and during polysomnographically monitored sleep. Esophageal pH was recorded by two sensors located in the mid- and proximal esophagus at 10 and 15 cm above the lower esophageal sphincter. RESULTS: Acid volume clearly increased the incidence of migration to the mid and proximal sensors during both waking and sleep, and also significantly increased acid clearance time. Posture failed to significantly affect the incidence of acid migration and acid clearance. Sleep clearly enhanced migration to the proximal pH sensor of even those perfusions as small as 1 ml. For instance, 40% of 1 ml perfusions during sleep migrated to the proximal sensor compared with <1% during waking. Acid clearance times were significantly longer during sleep as measured by the mid- and proximal esophageal pH sensors. CONCLUSIONS: In healthy individuals, volume enhances the likelihood of migration to both mid- and proximal esophagus, and significantly prolongs clearance time in the waking state. Posture appears to be a less significant parameter with regard to both the incidence of acid migration and acid clearance. Sleep is a significant risk factor for acid migration to the proximal esophagus for even minute volumes, and markedly prolongs acid clearance.

Performance by normal subjects on the Shipley Institute of Living Scale.

The usefulness of the Shipley Institute for Living Scale is limited by the lack of norms on middle-aged and older adults. This study reports data from 254 normal subjects aged 20 to 29 to 50 and older.

Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis.

BACKGROUND: Recently, several studies have shown an alteration in bowel function during sleep in patients with irritable bowel syndrome (IBS), and a recent study also suggests a remarkable increase in rapid eye movement (REM) sleep. These studies have suggested that an alteration in CNS function may play an important role in the pathogenesis of IBS. AIMS: To confirm the presence of an alteration in REM sleep in patients with IBS and to assess the relation between sleep and a non-invasive measure of gastric functioning, the electrogastrogram (EGG). PATIENTS: Ten patients with IBS and 10 age and sex matched normal volunteers. METHODS: All subjects slept one night in the sleep laboratory and underwent polysomnographic monitoring to determine sleep patterns, and recording of the EGG from surface electrodes. RESULTS: The IBS group had a notable and significant increase in the percentage and duration of REM sleep (p < 0.05). The control group had a decrease in the amplitude of the dominant EGG frequency from waking to non-REM sleep (p < 0.05), and a subsequent increase in the amplitude from non-REM to REM sleep (p < 0.05). No such changes were noted in the patients with IBS. CONCLUSIONS: Results confirmed the enhancement of REM sleep in patients with IBS and suggested an intrinsic alteration in autonomic and CNS functioning in patients with IBS.