Sleep biosignature of Type 2 diabetes: a case-control study.

AIM: To determine whether or not the sleep disturbances associated with Type 2 diabetes affect the structure of sleep. METHODS: We designed a case-control study in 76 patients with Type 2 diabetes and 76 control subjects without Type 2 diabetes, matched by age, gender, BMI and waist and neck circumferences. A subgroup of 32 patients with Type 2 diabetes was also matched with 64 control subjects without Type 2 diabetes according to apnoea-hypopnoea index score. Examination included an overnight full polysomnography. RESULTS: No differences in the percentage of time spent in either rapid eye movement or non-rapid eye movement sleep were observed between groups; however, patients with Type 2 diabetes had more microarousal events during sleep than control subjects [41.4 (total range 4.0-104.4) vs 20.7 (total range 1.3-94.5) events/h; P < 0.001]. These differences were mainly observed during the non-rapid eye movement sleep [7.4 (total range 0-107.2) vs 0.2 (total range 0-65.2) events/h; P < 0.001]. In addition, sleep variables related to oxygen saturation measures, such as the percentage of time spent with oxygen saturation ≤90%, were significantly greater during the rapid eye movement sleep in patients with Type 2 diabetes [20.3 (total range 0-99.2) vs. 10.5 (total range 0-94.0)%; P = 0.047]. This pattern was maintained in the subgroup of patients matched by apnoea-hypopnaea index. Finally, stepwise regression analyses showed that apnoea-hypopnoea index, the presence of Type 2 diabetes and fasting plasma glucose value were independently associated with the number of microarousals (R2 =0.667). CONCLUSIONS: Type 2 diabetes is associated with an altered sleep structure, with different effects according to rapid eye movement (increase in nocturnal hypoxia) or non-rapid eye movement (increase in sleep fragmentation) sleep.

Intermittent hypoxia is an independent marker of poorer glycaemic control in patients with uncontrolled type 2 diabetes.

AIM: This study investigated the association between intermittent hypoxia and glycaemic control in patients with uncontrolled type 2 diabetes (T2D) not treated for sleep apnoea. METHODS: This was a single-centre cross-sectional study of stable patients with T2D and HbA1c ≥7% (53 mmol/mol). Patients underwent overnight pulse oximetry and, if intermittent hypoxia-defined by a 4% oxyhaemoglobin desaturation index ≥15-was observed, respiratory polygraphy was performed. All participants completed the Pittsburgh Sleep Questionnaire and Hospital Anxiety and Depression Scale. The association between intermittent hypoxia and poorer glycaemic control (defined by an HbA1c level above the median of 8.5%) was estimated by multivariate logistic regression analysis. RESULTS: Out of 145 patients studied, 54 (37.2%) had intermittent hypoxia (with sleep apnoea confirmed in 53). Patients with intermittent hypoxia had 0.7% (7.7 mmol/mol) higher median HbA1c levels than patients without intermittent hypoxia (P=0.001). Intermittent hypoxia was associated with poorer glycaemic control after adjusting for obesity, age at onset and duration of diabetes, insulin requirement, sleep quality and depressive mood (OR: 2.31, 95% CI: 1.06-5.04, model adjusted for body mass index; OR: 2.46, 95% CI: 1.13-5.34, model adjusted for waist-to-height ratio). CONCLUSION: Intermittent hypoxia, a consequence of sleep apnoea, is frequent and has a strong independent association with poorer glycaemic control in patients with uncontrolled T2D.

Los ictus y su relación con el sueño y los trastornos del sueño / Strokes and their relationship with sleep and sleep disorders

Introducción: Los ictus son una causa importante de morbimortalidad en la población actual. Cada vez, a los ictus, se les han ido atribuyendo nuevos factores de riesgo. Últimamente está aumentando el interés de los trastornos del sue˜no y su influencia tanto como factor de riesgo y pronóstico en los ictus. Desarrollo: En este trabajo se exponen los cambios de la arquitectura del sue˜no y de la actividad cerebral en los pacientes con ictus, además de la interacción existente entre los ictus y los diferentes trastornos del sue˜no, así como los resultados de estas interacciones que modifican el transcurso de la enfermedad. Se enumeran los posibles tratamientos descritos hasta la actualidad, ya que un correcto tratamiento de estos trastornos del sue˜no no sólo puede mejorar la calidad de vida y disminuir las secuelas, sino mejorar las expectativas de vida de estos pacientes. Conclusiones: Los trastornos del sue˜no se están consolidando como una entidad asociada a los ictus, que en ocasiones puede ser un factor precursor, pero que también puede interferir en la evolución y en la recuperación posterior del ictus. Con este artículo pretendemos realizar una revisión exhaustiva de lo que se ha descrito hasta la actualidad en relación con los ictus, con el sue˜no y las alteraciones del mismo (AU)

Introduction: In the current population, strokes are one of the most important causes of morbidity and mortality, to which new risk factors are increasingly being attributed. Of late, there is increased interest in the relationship between sleep disorders and strokes as regards risk and prognosis. Development: This article presents the changes in sleep architecture and brain activity in stroke patients, as well as the interaction between stroke and sleep disorders, including those which may also influence the outcome and recovery from strokes. The different treatments discussed in the literature are also reviewed, as correct treatment of such sleep disorders may not only improve quality of life and reduce after-effects, but can also increase life expectancy. Conclusions: Sleep disorders are becoming increasingly associated with stroke. In addition to being a risk factor, they can also interfere in the outcome and recovery of stroke patients. This article aims to present an exhaustive and current review on strokes and their relationship with sleep alterations and sleep disorders (AU)

Strokes and their relationship with sleep and sleep disorders.

INTRODUCTION: In the current population, strokes are one of the most important causes of morbidity and mortality, to which new risk factors are increasingly being attributed. Of late, there is increased interest in the relationship between sleep disorders and strokes as regards risk and prognosis. DEVELOPMENT: This article presents the changes in sleep architecture and brain activity in stroke patients, as well as the interaction between stroke and sleep disorders, including those which may also influence the outcome and recovery from strokes. The different treatments discussed in the literature are also reviewed, as correct treatment of such sleep disorders may not only improve quality of life and reduce after-effects, but can also increase life expectancy. CONCLUSIONS: Sleep disorders are becoming increasingly associated with stroke. In addition to being a risk factor, they can also interfere in the outcome and recovery of stroke patients. This article aims to present an exhaustive and current review on strokes and their relationship with sleep alterations and sleep disorders.

TNF-α system and lung function impairment in obesity.

A potential interaction between pulmonary function, abnormal adipose tissue activity, and systemic inflammation has been suggested. This study explores the relationship between circulating soluble TNF-α receptors (sTNF-R1 and sTNF-R2) and respiratory function parameters in obese subjects. Thirty-one non-diabetic morbidly obese women with a history of non-smoking and without prior cardiovascular or respiratory disease were prospectively recruited in the outpatient Obesity Unit of a referral center. Pulmonary function test included a forced spirometry, static pulmonary volume measurements, non-attended respiratory polygraphy, and arterial gas blood sampling. Circulating levels of sTNFR-R1, sTNF-R2, interleukine 6 and adiponectin were determined using ELISA. Statistical analysis included a multivariate regression analysis taking into account the potential confounders. sTNF-R1 positively correlated with BMI (r=0.571, p=0.001) and arterial carbon dioxide pressure (PaCO(2), r=0.381, p=0.038), but negatively with forced expiratory volume in 1s (FEV(1), r=-0.437, p=0.012), maximum midexpiratory flow (FEF(25-75), r=-0.370, p=0.040) and forced vital capacity (FVC, r=-0.483, p=0.005). However, no correlation between sTNF-R2 and BMI and either pulmonary function tests or arterial blood samples was observed. Multiple linear regression analysis showed that sTNF-R1 independently predicted FEV(1) (beta=-0.437, p=0.012) and FVC (beta=-0.483, p=0.005). Thus, circulating levels of sTNF-R1, but not sTNF-R2, are related to reduced lung volumes and airflow limitation in morbidly obese patients prior to the development of a clinically recognized respiratory disease. Therefore, studies addressed to evaluating the potential beneficial effect of anti-TNF-α agents on pulmonary function tests in obese subjects seem warranted.

Type 2 diabetes impairs pulmonary function in morbidly obese women: a case-control study.

AIMS/HYPOTHESIS: To determine whether the presence of type 2 diabetes and the degree of metabolic control are related to reduced pulmonary function in obese individuals. METHODS: Seventy-five morbidly obese women (25 with type 2 diabetes [cases]--and 50 without diabetes [controls]) with a history of non-smoking and without prior cardiovascular or respiratory disease were prospective recruited for a case-control study in the outpatient obesity unit of a referral centre. Both groups were closely matched by age, BMI and waist circumference. Pulmonary function test included forced spirometry and static pulmonary volume measurements. RESULTS: Type 2 diabetic patients showed lower forced expiratory volume at 1 s (FEV1) (mean difference -11.6% of predicted [95% CI -20.4 to -2.8]; p = 0.011), and FEV1/forced vital capacity (FEV1/FVC) ratio (mean difference -4.4% [95% CI -8.1 to -0.7]; p = 0.049), but a greater residual volume (RV) (mean difference 19.5% of predicted [95% CI 10.8-28.3]; p < 0.001). In addition, an obstructive ventilatory pattern was more frequent in diabetic patients. Significant negative correlations between FEV1 and fasting glucose, HbA1c and HOMA insulin resistance (HOMA-IR) were detected. By contrast, RV was positively correlated with fasting glucose, HbA1c and HOMA-IR. Multiple linear regression analyses showed that fasting glucose and HbA1c independently predicted FEV1 and RV. CONCLUSIONS/INTERPRETATION: The presence of diabetes and the degree of glycaemic control are related to respiratory function impairment in morbidly obese women. Therefore, the impact of type 2 diabetes on pulmonary function should be taken into consideration by those providing care for obese people.

Accuracy and reliability of pulse oximetry at different arterial carbon dioxide pressure levels.

The present study aimed to assess whether arterial carbon dioxide pressure (Pa,CO(2)) has an impact on agreement between oxygen saturation measured with pulse oximetry (Sp,O(2)) or arterial blood gas co-oximetry (Sa,O(2)). Sa,O(2) and Sp,O(2) determinations were obtained simultaneously from 846 patients under assessment for long-term home oxygen therapy in a specialised outpatient clinic. Both measurements were taken with patients seated and breathing room air. Agreement between Sa,O(2) and Sp,O(2) results was analysed by the Bland-Altman method and the Lin concordance coefficient. In addition, potential interactions of arterial oxygen tension (Pa,O(2)) or Pa,CO(2) on agreement were analysed by adjusted multivariate analysis. Upon comparison of Sa,O(2) and Sp,O(2) results, the Bland-Altman technique yielded a bias (95% confidence interval (CI)) of -1.24 (-6.86-4.38) and -1.32 (-7.78-5.15) when Pa,CO(2) >48 mmHg (6.39 kPa) or Pa,O(2) <54 mmHg (7.20 kPa), respectively. Estimate by Lin's coefficient (95% CI) in these cases was 0.88 (0.85-0.90) and 0.81 (0.77-0.85). Adjusted multivariate analysis, performed to assess the impact of pH, Pa,O(2), Pa,CO(2) and bicarbonate on bias, showed that Pa,O(2), Pa,CO(2) and their interaction terms were the most important predictors of the bias (standardised estimates of -0.54, -0.94, and 0.85, respectively). The effect of pH, although statistically significant, was small, and bicarbonate had no significant effect. Arterial carbon dioxide pressure status can contribute to impaired agreement between arterial oxygen saturation and arterial oxygen saturation measured with pulse oximetry, particularly in patients with hypercapnia.

Mortality in severe sleep apnoea/hypopnoea syndrome patients: impact of treatment.

The aim of this study was to determine mortality in patients with sleep apnoea/hypopnoea syndrome (SAHS) according to the treatments employed and comorbidity. An historical cohort of patients with SAHS diagnosed at a university hospital between 1982 and 1992 and followed until 1996 was studied. From a total of 475 SAHS patients, 444 (94%), with a mean+/-SD apnoea/hypopnoea index at diagnosis of 55+/-27, were located and included in the study. SAHS treatments employed were: surgery (88), weight loss (134), continuous positive airway pressure (124) and 98 patients were not treated. By the end of follow-up, 49 patients had died. According to Cox regression analysis, mortality in treated patients was lower than in those not treated, but higher in those with a history of severe chronic obstructive pulmonary disease. Mortality in nontreated patients compared with that of the general population, adjusted for age and sex, showed excessive mortality, which decreased in treated patients. Stratification by age showed a greater mortality rate ratio in patients <50 yrs. These findings were maintained when mortality from cardiovascular causes was compared. In conclusion, a rise in mortality was found in nontreated sleep apnoea/hypopnoea syndrome patients compared with the general population, whereas mortality in those treated for sleep apnoea/hypopnoea syndrome did not differ significantly from that of the general population.

Influence of setting on unattended respiratory monitoring in the sleep apnoea/hypopnoea syndrome.

The high demand for full polysomnography and the better quality of sleep at home are the main reasons for performing home sleep studies. Home respiratory monitoring has been evaluated in several studies, but the influence of setting on the results of unattended respiratory monitoring has not been assessed to date. Unattended monitoring of respiratory variables at home and in the sleep laboratory was conducted in 35 consecutive patients with suspected sleep apnoea/hypopnoea syndrome. Respiratory variables during sleep, rate of successful studies and patient preference were compared. The data acquisition failure rate was 2.8% in the sleep laboratory and 5.7% at home. The mean difference between apnoea/hypopnoea indices (AHI) obtained from home and laboratory studies was -0.21 +/- 8 (95% confidence interval 3.27-2.84). Using the method comparison approach of Bland and Altman, the limits of agreement of the mean difference between AHI home and AHI laboratory were -16.7 and 17.1. No difference was observed between the studies in time spent in different body positions. When patients were asked where they would prefer to repeat the sleep study, 53% replied at home, 28% in hospital and 19% showed no preference. It was concluded that the setting of unattended respiratory monitoring (home or sleep laboratory) influences neither the number of valid studies nor the results of the respiratory parameters measured; most patients, however, preferred home studies.

Self-reported sleepiness while driving as a risk factor for traffic accidents in patients with obstructive sleep apnoea syndrome and in non-apnoeic snorers.

The obstructive sleep apnoea syndrome (OSAS) is a condition causing daytime sleepiness and has been related to an increased risk for traffic accidents. However, the evidence linking severity of OSAS to a higher rate of automobile crashes is based on limited data. The aims of this study were to study the traffic accident rate in the last 5 years in patients referred to our sleep clinic because of clinical suspicion of OSAS and to analyse variables related to an increased risk for traffic accidents. A series of 189 consecutive patients with a driving license referred for a sleep study because of OSAS clinical suspicion and a control group (CG) of 40 hospital staff workers who denied snoring, matched for age and sex with the study population, were studied. Patients underwent a full-night polysomnography and both patients and the CG completed a self-answered questionnaire. One hundred and twenty-two patients were diagnosed as OSAS and 67 patients as non-apnoeic snorers (NAS). The self-reported number of accidents was significantly higher in OSAS patients compared with CG. The self-reported number of times off the road was significantly higher in OSAS patients compared with NAS and with CG. Variables associated with an increased risk for traffic accidents were self-reported sleepiness while driving (OR 5, 95%CI 2.3-10.9), having quit driving because of sleepiness (OR 3, 95%CI 1.1-8.6) and being currently working (OR 2.8, 95%CI 1.1-7.7). We conclude that self-reported sleepiness while driving is associated with an increased risk for traffic accidents in OSAS patients and in NAS. We suggest that this symptom can be used to alert patients and to give priority in the sleep clinic for study and treatment.

Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa.

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.

Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome.

Weight loss is associated with clinical improvement in sleep apnoea/ hypopnoea syndrome (SAHS). The aim of this study was to ascertain whether the therapeutic efficacy of dietary weight loss is maintained in the long-term. From a total of 216 overweight SAHS patients treated by only a weight reduction programme, 24 cured by this method (apnoea/hypopnoea index (AHI) at diagnosis 443+/-27.8, after weight loss 3+/-3.1) were re-evaluated after a mean (+/-SD) period of 94.3+/-27.4 months post-cure. No correlation was found between changes in AHI and body mass index experienced by each patient in the two phases of the study (diagnosis to cure and cure to long-term follow-up), r=0.29, p=0.156, demonstrating a marked intra-individual variability. Six of the 13 patients who maintained their weight presented recurrence of SAHS (AHI 40.5+/-24.1) as did eight of the 11 who had regained weight (AHI 44.3+/-23.). Weight maintenance was more frequent among patients who had continued to attend periodic appointments, 10/11 versus 3/13 (p<0.001). In conclusion, weight-loss efficacy is maintained in the long-term in some sleep apnoea/hypopnoea syndrome patients. This study indicates the need for periodic follow-up of these patients as a reinforcement for weight maintenance and for early detection of the reappearance of sleep apnoea/hypopnoea syndrome.

Acute delirium as a manifestation of obstructive sleep apnea syndrome.

Cognitive deficits and psychiatric manifestations such as depression and psychosis have been associated with obstructive sleep apnea (OSA) syndrome. We report a patient with OSA admitted to our center because of acute delirium of sudden onset at night, during sleep, and which impelled the patient to jump out of the window of his home. After exhaustive study, no other causes were found for the delirium, which resolved when nasal continuous positive airway pressure (nCPAP) was initiated. We believe that it is clinically important to be aware of this association, since it identifies a new, treatable cause of delirium.

Survival prognostic factors and markers of morbidity in Spanish patients with systemic sclerosis.

OBJECTIVE: To identify survival prognostic factors and markers of morbidity among patients with systemic sclerosis (SSc). PATIENTS AND METHODS: The study included 72 patients diagnosed with SSc. According to the extent of skin involvement, three groups of patients were established: group 1, without sclerosis and with sclerosis of fingers and neck; group 2, with sclerosis of face and distal to elbows and knees; group 3, with generalised sclerosis including the trunk. All patients were included in a study protocol to determine visceral involvement. Cumulative survival after first symptom has been estimated according to the Kaplan-Meier method. The association between a hypothetical prognostic factor and cumulative survival after first symptom was assessed by log rank test. The association between a hypothetical risk factor and the prevalence of severe morbidity was assessed by the odds ratio. Multiple logistic regression models were used to identify the main predictors of severe morbidity. RESULTS: Survival was estimated to be 85% 10 years after first SSc symptom. Survival was higher among SSc patients with skin involvement distal to elbows and knees than among the rest of patients; a forced vital capacity (FVC) on spirometry lower than 70% of expected value was associated with a shorter survival, even after adjustment for diffuse SSc. Skin involvement proximal to elbows or knees was associated with a higher prevalence of severe morbidity (OR = 46.57; p < 0.001). According to a multiple logistic regression, severe morbidity was higher among patients with skin involvement proximal to knees or elbows (OR = 40.92; p < 0.001) or among patients with pulmonary hypertension detected by Doppler echocardiography (OR = 23.66 p < 0.001). CONCLUSIONS: In patients with SSc the extent of skin sclerosis was found to be a determining factor on the prognosis. According to skin sclerosis extent two main subsets of SSc patients with different survival incidence and degree of morbidity could be clearly established: limited SSc, formed by patients with no skin sclerosis or with sclerosis distal to elbows and knees and diffuse SSc, formed by patients with skin sclerosis distal and proximal to elbows and knees. Moreover, lung involvement (FVC < 70% on survival study and pulmonary hypertension on morbidity study) was an important and independent prognostic factor.

Nasal continuous positive airway pressure with supplemental oxygen in coexistent sleep apnoea-hypopnoea syndrome and severe chronic obstructive pulmonary disease.

The objective of our study was to assess the application of nasal continuous positive airway pressure (nCPAP) with supplemental oxygen for correction of upper airway obstructive episodes and hypoxaemia during sleep in stable patients with sleep apnoea-hypopnoea syndrome (SAHS) and severe chronic obstructive pulmonary disease (COPD). Ten male patients with symptomatic SAHS and severe COPD (forced expiratory volume in one second < 50% of predicted) were studied for three consecutive nights. Diagnostic polysomnography was performed the first night and repeated with increasing nCPAP levels, with and without supplemental oxygen on the second and third nights, respectively. Diagnostic polysomnography showed: mean (SD) apnoea-hypopnoea index 41 (22) events.h-1; mean arterial oxygen saturation (Sa,O2) was 86 (2)% and mean desaturation nadir was 81 (4)% during non-rapid eye movement (nREM) sleep and 80 (7)% and 73 (9)%, respectively during REM sleep. The application of nCPAP during the second night corrected apnoeas and hypopnoeas, but mean Sa,O2 remained < 90% in all patients. With the addition of oxygen at a flow of 1.5 L.min-1 at suboptimal nCPAP levels, we observed an increase in apnoea frequency, persistence of apnoeas at nCPAP levels which eliminated them when no supplemental oxygen was administered, and longer duration of apnoeas and hypopnoeas. However, when the effective nCPAP level of the second night was reached with supplemental oxygen during the third night, its efficacy in eliminating apnoeas and hypopnoeas was maintained and, furthermore, all patients presented Sa,O2 > 90%, with no greater hypercapnia cardiac arrhythmias. We conclude that nasal continuous positive airway pressure with supplemental oxygen constitutes a practical therapeutic alternative for hypoxic patients with sleep apnoea-hypopnoea syndrome and chronic obstructive pulmonary disease.