No abstract

Abstract. Elmasry A, Lindberg E, Berne C, Janson C, Gislason T, Awad Tageldin M, Boman G (Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden; Ain Shams University, Cairo, Egypt; and Vi®lsstadir Hospital, Gardabaer, Iceland). Sleepdisordered breathing and glucose metabolism in hypertensive men: a population-based study. J Intern Med 2001; 249: 153±161.

Abstract. Elmasry A, Janson C, Lindberg E, Gislason T, Tageldin MA, Boman G (Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden; Ain Shams University, Cairo, Egypt; and Viffilsstadir Hospital, Gardabñr, Iceland). The role of habitual snoring and obesity in the development of diabetes: a 10-year follow-up study in a male population. J Intern Med 2000; 248: 13±20.Objectives. There are many similarities between diabetes (mainly type 2) and sleep breathing disturbances regarding risk factors, anthropometric criteria and consequences of morbidity and mortality. The aim of this study was to investigate whether the association between habitual snoring and diabetes is entirely dependent on obesity. Design. A population-based prospective study. Setting. The municipality of Uppsala, Sweden. Subjects and methods. In 1984 and in 1994, 2668 men aged 30±69 years at baseline answered questionnaires concerning sleep breathing disturbances and somatic diseases.Results. Of those with habitual snoring in 1984, 5.4% reported that they had developed diabetes during the 10-year period compared with 2.4% of those without habitual snoring (P , 0.001). Amongst obese snorers, 13.5% developed diabetes compared with 8.6% of obese non-snorers (P = 0.17). In a multiple logistic regression model, the odds ratio (95% confidence interval) for development of diabetes was higher in obese snorers [7.0 (2.9±16.9)] than in obese non-snorers [5.1 (2.7±9.5)] after adjustment for age, weight gain, smoking, alcohol dependence and physical inactivity. Conclusions. We conclude that, in males aged 30± 69 years, habitual snoring is associated with an increased incidence of diabetes within 10 years. Although obesity is the main risk factor for developing diabetes, coexistent habitual snoring may add to this hazard.

No abstract

Background: Several studies have reported an association between sleep disordered breathing (SDB) and hypertension (HT) but there is still a debate as to whether this is an effect of confounders. Some researchers have found an age dependent relationship between SDB and HT with higher risk at lower ages. A case-control study was performed in hypertensive men and non-hypertensive male controls matched for age and body mass index to assess whether there is an independent association between SDB and HT. If so, we further wanted to investigate whether this effect is age dependent. Methods: An overnight sleep study was performed in a population based, age stratified sample of 102 hypertensive men aged 43-82 years and 102 non-hypertensive controls. Results: Hypertensive subjects had a significantly higher prevalence of SDB than non-hypertensive subjects (apnoea-hypopnoea index (AHI): 10.8 v 7.3; desaturation index (DI): 8.5 v 5.2; AHI >10: 37% v 24%, p<0.05; DI >10: 29% v 12%; lowest desaturation: mean (SD) 81.9 (7.3) v 84.7 (6.1), p<0.01). After adjusting for neck circumference and physical inactivity, DI >10 and lowest desaturation were still independent predictors of HT with adjusted odds ratios of 2.3 (95% CI 1.0 to 5.3) and 0.94 (95% CI 0.89 to 0.99), respectively. When the subjects were split into two groups according to age (<60 and >60 years), the influence of DI >10 on HT was strongest in the younger men (adjusted OR 4.3 (95% CI 1.0 to 19.3 v 2.1 (95% CI 0.7 to 6.5)) and the association between minimum oxygen saturation (SaO 2 ) and HT reached statistical significance in the younger men only. Conclusion: SDB is more prevalent in men with HT than in controls. DI >10 and lowest desaturation are independent predictors of HT irrespective of confounders. The results indicate that the influence of SDB on HT is more pronounced in younger and middle aged men than in those above 60 years.

This study followed a small number of men previously studied polysomnographically 10 yr earlier to investigate the relationship between the development of sleep-disordered breathing and age, weight gain, and smoking. In 1984, 3,201 men answered a questionnaire including questions about snoring and excessive daytime sleepiness (EDS). Of those reporting symptoms related to obstructive sleep apnea syndrome (OSAS), a random sample of 61 men was investigated using whole-night polysomnography in 1985. Ten years later, 38 men participated in the present follow-up, which included a structured interview and polysomnography. During the 10-yr period, nine men had been treated for OSAS. Of the 29 untreated subjects, the number of men with OSAS, defined as an apnea-hypopnea index (AHI) of >/= 5/h, increased from four in 1985 to 13 in 1995 (p < 0.01). In this small sample, no significant associations were found between DeltaAHI (i.e., AHI 1995 - AHI 1985) and age, weight gain, or smoking. We conclude that, among this small group of individuals who were selected for original polysomnographic study and follow-up because they were thought to have symptoms of sleep apnea, sleep-disordered breathing became significantly worse over time.

Studies addressing the relationship between obstructive sleep apnoea (OSA) and sympathoadrenal activity have been criticized for poor control of factors known to confound sympathetic function, including hypertension. The aim of this study was to investigate the relationship between OSA and urinary catecholamines in a population-based sample of hypertensive males.In 1994, 2,668 males aged 40-79 yrs answered a questionnaire regarding sleep disorders and somatic diseases. Of those who reported hypertension, an age-stratified sample of 116 was selected for monitoring of breathing during sleep and overnight urine analysis.Subjects with OSA, defined as apnoea-hypopnoea index ¢10?h -1 , had higher concentrations of urinary normetanephrine (182¡57 versus 141¡45 mmol?mol -1 creatinine, pv0.001) and metanephrine (70¡28 versus 61¡28 mmol?mol -1 creatinine, pv0.05) in comparison to subjects without OSA. In a multiple regression analysis, there was an association between variables of sleep-disordered breathing and normetanephrine and metanephrine concentrations, independent of major confounding factors.The authors concluded that, in a population-based sample of hypertensive males, obstructive sleep apnoea is associated with increased urinary concentrations of extraneuronal metabolites of catecholamines independent of major confounding factors, suggesting increased sympathoadrenal activity. Elevated sympathoadrenal activity may explain the increased cardiovascular morbidity associated with obstructive sleep apnoea.

Background & AimsPatients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte−associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86), is a negative regulator of T-cell activation. We collected T cells from patients with ALF and investigated whether inhibitory signals down-regulate adaptive immune responses in patients with ALF.MethodsWe collected peripheral blood mononuclear cells from patients with ALF and controls from September 2013 through September 2015 (45 patients with ALF, 20 patients with acute-on-chronic liver failure, 15 patients with cirrhosis with no evidence of acute decompensation, 20 patients with septic shock but no cirrhosis or liver disease, and 20 healthy individuals). Circulating CD4+ T cells were isolated and analyzed by flow cytometry. CD4+ T cells were incubated with antigen, or agonist to CD3 and dendritic cells, with or without antibody against CTLA4; T-cell proliferation and protein expression were quantified. We measured levels of soluble B7 molecules in supernatants of isolated primary hepatocytes, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays.ResultsPeripheral blood samples from patients with ALF had a higher proportion of CD4+ CTLA4+ T cells than controls; patients with infections had the highest proportions. CD4+ T cells from patients with ALF had a reduced proliferative response to antigen or CD3 stimulation compared to cells from controls; incubation of CD4+ T cells from patients with ALF with an antibody against CTLA4 increased their proliferative response to antigen and to CD3 stimulation, to the same levels as cells from controls. CD4+ T cells from controls up-regulated expression of CTLA4 after 24−48 hours culture with sera from patients with ALF; these sera were found to have increased concentrations of soluble B7 compared to sera from controls. Necrotic human primary hepatocytes exposed to acetaminophen, but not hepatic sinusoidal endothelial cells and biliary epithelial cells from patients with ALF, secreted high levels of soluble B7. Sera from mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells.ConclusionsPeripheral CD4+ T cells from patients with ALF have increased expression of CTLA4 compared to individuals without ALF; these cells have a reduced response to antigen and CD3 stimulation. We found sera of patients with ALF and from mice with liver injury to have high concentrations of soluble B7, which up-regulates CTLA4 expression by T cells and reduces their response to antigen. Plasma exchange reduces level...