Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime

Chronic insomnia, by far the most commonly encountered sleep disorder in medical practice, is characterized by difficulty falling or staying asleep at night and increased fatigue during the day. Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are fatigue-inducing cytokines, and the daytime secretion of IL-6 is negatively influenced by the quantity and quality of the previous night's sleep. We hypothesize that the poor quality of insomniacs' sleep is associated with a hypersecretion of these 2 cytokines during the daytime, which, in turn, correlates with the fatigue experienced by these patients. Eleven young insomniacs (6 men and 5 women) and 11 (8 men and 3 women) age- and body mass index (BMI)-matched healthy controls participated in the study. Subjects were recorded in the sleep laboratory for 4 consecutive nights and serial 24-hour plasma measures of IL-6 and TNF were obtained during the 4th day. Insomniacs compared to controls slept poorly (sleep latency and wake were increased, whereas percentage sleep time was decreased during baseline nights, all P <.05). The mean 24-hour IL-6 and TNF secretions were not different between insomniacs and controls. However, the difference in the change (increase) of IL-6 plasma levels from midafternoon (2 PM) to evening (9 PM) between insomniacs and controls was significant (P <.01). Furthermore, cosinor analysis showed a significant shift of the major peak of IL-6 secretion from nighttime (4 AM) to evening (7 PM) in insomniacs compared to controls (P <.05). Also, while TNF secretion in controls showed a distinct circadian rhythm with a peak close and prior to the offset of sleep (P <.05), such a rhythm was not present in insomniacs. Finally, daytime secretion of TNF in insomniacs was characterized by a regular rhythm of 4 hours (P <.05); such a distinct periodicity was not present in controls. We conclude that chronic insomnia is associated with a shift of IL-6 and TNF secretion from nighttime to daytime, which may explain the daytime fatigue and performance decrements associated with this disorder. The daytime shift of IL-6 and TNF secretion, combined with a 24-hour hypersecretion of cortisol, an arousal hormone, may explain the insomniacs' daytime fatigue and difficulty falling asleep.     

Epidemiology and treatment of the metabolic syndrome

Recent definitions of the metabolic syndrome from the World Health Organization (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer picture of the prevalence of the metabolic syndrome and the risks it poses for cardiovascular disease and type 2 diabetes. Solid epidemiological and trial evidence support lifestyle changes as the main modifiable risk factors, including abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low in fiber content, in the treatment of individual components of the metabolic syndrome. Physical activity may prevent the metabolic syndrome as defined by the WHO and NCEP, but the evidence for lifestyle changes using these definitions is still sparse. No trials on the treatment of the metabolic syndrome to prevent diabetes have been published. However, both the Finnish Diabetes Prevention Study and the Diabetes Prevention Program found that moderate lifestyle interventions in persons with impaired glucose tolerance, a condition related to the metabolic syndrome, decreased the incidence of type 2 diabetes by 58%. Some drugs may also prevent diabetes. Further research on lifestyle modifications in the prevention and treatment of the metabolic syndrome, and on how best to promote lifestyle changes, is needed. In the meantime, efforts to curb obesity and overweight, increase physical activity and improve compliance with current dietary recommendations should continue.     

Selective effects of CPAP on sleep apnoea-associated manifestations

Background   Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.
Materials and methods   Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP.
Results   At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls ( P  < 0·05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels ( P  < 0·05). CPAP decreased daytime sleepiness and blood pressure ( P  < 0·05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-α, or TNF-r1 levels.
Conclusions   In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.     

Association of waist and hip circumference with 12-year progression of carotid intima-media thickness in elderly women

OBJECTIVE: To test the hypothesis that waist and hip circumferences together provide additional information on the progression of preclinical atherosclerosis beyond either of them alone in elderly women. DESIGN: A 12-year follow-up study. SUBJECTS: A population-based sample of 102 women 60-70 years of age at baseline. MEASUREMENTS: Waist and hip circumferences and body mass index (BMI) were assessed and carotid intima-media thickness (IMT) was quantified noninvasively by ultrasonography. RESULTS: There was a significant increase in the 12-year carotid IMT progression across the thirds of waist circumference (0.080, 0.277, 0.279 mm, P=0.02 for difference) and hip circumference (0.030, 0.342, 0.260 mm, P=0.001 for difference) adjusted for conventional risk factors (age, smoking, systolic blood pressure, serum low-density lipoprotein and high-density lipoprotein cholesterol, blood glucose). The association of waist circumference with IMT progression was not significant after further adjustment for hip circumference or BMI. Further adjustment for waist circumference and BMI did not change the association of hip circumference with IMT progression. The IMT progression was greatest in women with waist circumference >83 cm and hip circumference 相似文献   

Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-alpha antagonist

The proinflammatory cytokines, TNFalpha and IL-6, are elevated in obstructive sleep apnea (OSA) and have been proposed as mediators of excessive daytime sleepiness in humans. We tested the effects of etanercept, a medication that neutralizes TNFalpha and is approved by the FDA for the treatment of rheumatoid arthritis, in eight obese male apneics. These patients participated in a pilot, placebo-controlled, double-blind study during which nighttime polysomnography, multiple sleep latency test, and fasting blood glucose and plasma levels of IL-6, C-reactive protein, insulin, and adiponectin were obtained. There was a significant and marked decrease in sleepiness by etanercept, which increased sleep latency during the multiple sleep latency test by 3.1 +/- 1.0 min (P < 0.05) compared with placebo. Also, the number of apneas/hypopneas per hour was reduced significantly by the drug compared with placebo (52.8 +/- 9.1 vs. 44.3 +/- 10.3; adjusted difference, -8.4 +/- 2.3; P < 0.05). Furthermore, IL-6 levels were significantly decreased after etanercept administration compared with placebo (3.8 +/- 0.9 vs. 1.9 +/- 0.4 pg/ml; adjusted difference, -1.9 +/- 0.5; P < 0.01). However, no differences were observed in etanercept vs. placebo in the levels of fasting blood glucose and plasma C-reactive protein, insulin, and adiponectin. We conclude that neutralizing TNFalpha activity is associated with a significant reduction of objective sleepiness in obese patients with OSA. This effect, which is about 3-fold higher than the reported effects of continuous positive airway pressure on objective sleepiness in patients with OSA (0.9 vs. 3.1 min), suggests that proinflammatory cytokines contribute to the pathogenesis of OSA/sleepiness.     

Recommendations for personal respiratory protection in tuberculosis

These recommendations of the German Central Committee against Tuberculosis give an overview of the current scientific knowledge on the tuberculosis risk of health service employees and on the risk of infection in individual areas of work. The efficacy of face masks and their benefit in tuberculosis control is discussed. There are no reliable data on the efficacy of face masks in preventing infection with M. tuberculosis, nor can such data be expected in the near future, due to the complex interaction of infection-preventing measures. As rapid case finding, isolation, and immediate, effective treatment of infected patients already greatly diminish the risk of transmission, we consider face masks to be of limited use in reducing this risk. However, they may be beneficial in certain areas of work and in certain situations, particularly in the presence of elevated aerosol concentrations. The benefit of face masks depends largely on their correct application. The choice of a particular type of mask requires knowledge of the current epidemiological situation, and a competent assessment of the risk in the area of work for which it is chosen, taking into account the closeness of contact with potentially infectious tuberculosis patients.     

Low physical activity as a predictor for antihypertensive drug treatment in 25-64-year-old populations in eastern and south-western Finland

OBJECTIVE: To determine whether low leisure-time physical activity, occupational physical activity and commuting activity independently increase the risk of hypertension when adjusted for most risk factors for hypertension and for different forms of physical activity. DESIGN: Population-based prospective cohort study. SETTING: Eastern and south-western Finland. PARTICIPANTS: Men (n = 5935) and women (n = 6227) aged 25-64 years. MAIN OUTCOME MEASURE: Initiation of free-of-charge medication for hypertension during a mean follow-up time of 11.3 years. RESULTS: Men with high leisure-time physical activity had a reduced risk of hypertension when adjustment had been made for age, area and year of survey, education, smoking, alcohol intake, baseline systolic blood pressure (SBP), body mass index (BMI), commuting activity and occupational physical activity [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.63 to 0.99]. Women with high leisure-time physical activity had a reduced risk of hypertension when adjusted for age, area and time of survey (HR 0.65; 95% CI 0.46 to 0.91). This association was no longer significant when further adjustments were made for other covariates (HR 0.73; 95% CI 0.52 to 1.03). High occupational physical activity reduced the risk of hypertension only among men and women combined when adjustment was made for age, area and time of survey, education, smoking and alcohol intake, in addition to baseline SBP, BMI, commuting activity and leisure-time physical activity (HR 0.83; 95% CI 0.72 to 0.96). Commuting activity was not associated with risk of hypertension in multivariate models. CONCLUSION: High levels of leisure-time physical activity are associated with a reduced risk of hypertension, independently of most common risk factors for hypertension, occupational physical activity and commuting activity. Promoting leisure-time physical activity is essential to prevent hypertension.     

Clustering of Metabolic Risk Factors Is Associated with High-Normal Levels of Liver Enzymes Among 6- to 8-Year-Old Children: The PANIC Study

Abstract Background: We studied the associations of clustering of metabolic risk factors with plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in healthy prepubertal children. Methods: The subjects were a representative population sample of 492 children 6-8 years of age. We assessed body fat percentage (dual-energy X-ray absorptiometry), body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, ALT, GGT, and high-sensitivity C-reactive protein (hsCRP) and calculated a continuous metabolic syndrome score variable. We also used factor analysis to examine whether high-normal liver enzymes are a feature of metabolic syndrome among children. Results: Children with overweight or obesity, defined by International Obesity Task Force (IOTF) criteria, had a 2.1-times higher risk of having ALT and a 4.5-times higher risk of having GGT in the highest fifth of its distribution than normal weight children. Children in the highest sex-specific third of metabolic syndrome score, body fat percentage, waist circumference, and insulin had a two to three times higher risk of being in the highest fifth of ALT and GGT. Moreover, children in the highest third of glucose and hsCRP had a 2.5-fold risk of being in the highest fifth of GGT. First-order factor analysis yielded three factors; the first included insulin, glucose, and triglycerides; the second waist circumference, insulin, GGT, and hsCRP; and the third HDL-C, triglycerides, waist circumference, and insulin. Second-order factor analysis yielded a single metabolic syndrome factor, explaining 64.1% of the variance. Conclusions: Clustering of metabolic risk factors, particularly excess body fat, is associated with high-normal levels of ALT and GGT in prepubertal children. High-normal levels of liver enzymes, especially GGT, and systemic low-grade inflammation could be considered features of metabolic syndrome among children. Subtle changes in liver function may play an important role in the pathogenesis of metabolic syndrome beginning in childhood.     

Systolic blood pressure during recovery from exercise and the risk of acute myocardial infarction in middle-aged men

We prospectively assessed the association of systolic blood pressure (SBP) after exercise with the risk of an acute myocardial infarction. Limited information exists currently on the role of SBP during recovery period with the risk of acute myocardial infarction. SBP was measured every 2 minutes during and after a progressive cycle ergometer exercise test in a representative sample of 2336 men (aged 42 to 61 years). During an average follow-up period of 13.1 years, 358 acute myocardial infarctions occurred. An incremental rise of 10 mm Hg per minute in SBP at 2 minutes after exercise (relative risk, 1.07-fold; 95% confidence interval [CI], 1.03 to 1.12; P=0.001) was associated with the risk of acute myocardial infarction after adjustment for age, alcohol consumption, smoking, serum lipids, diabetes mellitus, body mass index, resting SBP, regular use of antihypertensive medications, physical fitness, heart rate, and ischemic ECG findings during exercise. Men with elevated SBP of >195 mm Hg after exercise had a 1.69-fold (95% CI, 1.24 to 2.30; P=0.001) risk for an acute myocardial infarction compared with those with SBP <170 mm Hg after adjustment for age, other risk factors, and resting SBP. SBP after exercise provides an incremental predictive value for acute myocardial infarction beyond that of resting SBP. This emphasizes the importance of SBP measurements after the exercise test because it provides additional valuable prognostic measure with regard to acute myocardial infarction.