Characteristics of obstructive sleep apnea related to insulin resistance.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with multiple comorbidities, including diabetes. Its development is preceded by alterations in the initial phase of carbohydrate metabolism characterized by insulin resistance. This study aims to evaluate the role of intermittent hypoxia and sleep fragmentation characteristic of OSA on the risk of insulin resistance among apneic patients without diabetes. METHODOLOGY: 92 consecutive patients with OSA without evidence of diabetes were recruited. Overnight video polysomnography was performed and, the following morning, fasting blood glucose, insulin and glycosylated hemoglobin were determined. Insulin resistance was measured using the HOMA-IR index. RESULTS: Insulin resistance was present in 52.2% of OSA patients. In these subjects, insulin resistance was independently associated to the apnea index during REM sleep (adjusted odds ratio [aOR] 1.09; 95% CI, 1.03 to 1.16; p = 0.004), desaturation index (aOR 1.08; 95% CI: 1.04 to 1.13; p = 0.027), and sleep time with oxygen saturation below 90% (aOR 1.04; 95% CI 1.00 to 1.08; p = 0.049). Furthermore, the HOMA-IR level was also directly related to the desaturation index (standardized regression coefficient [B] = 0.514, p < 0.001) and to the apnea index during REM sleep (B = 0.344, p = 0.002). CONCLUSIONS: Intermittent hypoxia and disturbances in REM sleep emerge as main contributors to insulin resistance in OSA patients yet to experience diabetes onset.

Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea.

Rationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1ß, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Measurements and Main Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1ß and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α-dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.

Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea.

As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)ß-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFß, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFß induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFß activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA.

Contribution of sleep characteristics to the association between obstructive sleep apnea and dyslipidemia.

OBJECTIVES/BACKGROUND: Little information is available about the association of obstructive sleep apnea (OSA) with atherogenic dyslipidemia and the contribution of sleep characteristics to lipid alterations. We compare dyslipidemia prevalence among non-apneic subjects and mild-severe OSA patients to identify the sleep characteristics that are independently associated with dyslipidemia and serum lipid levels in OSA patients. PATIENTS/METHODS: We recruited 809 consecutive patients who had been referred for polysomnography study by OSA suspicion. Anthropometric characteristics, body composition and comorbidities were recorded. Spirometry and 24-h ambulatory blood pressure monitoring were performed the same day of the sleep study. The day after attended polysomnography, fasting blood samples were drawn to measure the lipid profile. RESULTS: Dyslipidemia prevalence increased with the presence of OSA, from non-OSA subjects to mild, moderate and severe OSA patients (31%, 33%, 42% and 51%, respectively; p < 0.001). After adjusting for sex, age, body mass index and smoking habit, only severe OSA had an independent association with dyslipidemia when compared to non-OSA subjects (adjusted odds ratio 1.71, 95%CI 1.09 to 2.69, p = 0.019). In OSA patients, multivariate logistic regression identified active smoking, apnea-hypopnea index (AHI) and mean nocturnal saturation as variables independently associated with dyslipidemia. However, in these patients, arousal index, slow wave sleep duration and REM latency were also independently associated with cholesterol and low-density lipoprotein levels. CONCLUSIONS: The association between dyslipidemia and OSA is limited to severe patients, with high AHI and nocturnal hypoxemia. However, sleep fragmentation and increased sympathetic activity could also contribute to OSA-related lipid dysregulation.

SMAD4 Overexpression in Patients with Sleep Apnoea May Be Associated with Cardiometabolic Comorbidities.

Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic and cardiovascular risk. Although the mechanisms involved in the development of these disorders may vary, OSA patients frequently present an increase in transforming growth factor beta (TGFß), the activity of which is higher still in patients with hypertension, diabetes or cardiovascular morbidity. Smad4 is a member of the small mother against decapentaplegic homologue (Smad) family of signal transducers and acts as a central mediator of TGFß signalling pathways. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with an apnoea-hypopnoea index (AHI) ≥30 and 26 healthy volunteers. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in HIF1α, mTOR and circadian genes. Moreover, we associated high concentrations of Smad4 plasma protein with the presence of diabetes, dyslipidaemia and hypertension in these patients. Results suggest that increased levels of SMAD4, mediated by intermittent hypoxaemia and circadian rhythm deregulation, may be associated with cardiometabolic comorbidities in patients with sleep apnoea.

Tratamiento por teléfono del tabaquismo. Factores predictivos de éxito / Telephone-based smoking cessation. Predictors of success

Fundamento y objetivo: Evaluar los factores predictivos de éxito del tratamiento telefónico del tabaquismo. Pacientes y métodos: Estudio observacional realizado en el contexto de la práctica clínica en una Unidad de Tabaquismo. Programa de tratamiento por teléfono durante 3 meses y seguimiento hasta los seis meses. Se analizaron variables sociodemográficas, de dependencia y comorbilidad, y como variable principal la abstinencia continua a las 24 semanas. Resultados: Se incluyeron 743 sujetos (43% varones y 57% mujeres), con edad media (DE) de 41,9 (9,8) años. La abstinencia continua fue del 37,3% (intervalo de confianza del 95% [IC 95%] 34,9-40,0). El modelo multivariable mostró tres variables con valor predictivo: no padecer trastorno psiquiátrico, vivir en pareja y el primer ítem del test de Fagerström. Conclusiones: El resultado del programa de tratamiento estuvo condicionado por las siguientes variables del fumador: la dependencia a la nicotina, la patología psiquiátrica y el soporte social (AU)

Background and objective: To identify the predictors of successful outcome in a telephone smoking cessation program. Patients and methods: Observational study in the context of clinical practice in a smoking cessation clinic. The smoking cessation program was carried out by phone over a period of 3 months and follow-up for 6 months. Sociodemographic variables were analyzed, dependence, and comorbidity and the main variable was continuous abstinence at 24 weeks. Results: 743 smokers, 43% male and 57% female, mean (SD) age: 41.9 (9.8) years. The continuous abstinence rate at 24 weeks was 37.3% (IC 95% 34.9-40.0).The multivariable model showed three variables with predictive value: no current psychiatric diagnosis, social support and the first item of Fagerström test (time to first cigarette in the morning). Conclusions: Treatment outcomes of this smoking cessation program was influenced by the following variables: nicotine dependence, psychiatric disorders and social support (AU)

[Telephone-based smoking cessation. Predictors of success]. / Tratamiento por teléfono del tabaquismo. Factores predictivos de éxito.

BACKGROUND AND OBJECTIVE: To identify the predictors of successful outcome in a telephone smoking cessation program. PATIENTS AND METHODS: Observational study in the context of clinical practice in a smoking cessation clinic. The smoking cessation program was carried out by phone over a period of 3 months and follow-up for 6 months. Sociodemographic variables were analyzed, dependence, and comorbidity and the main variable was continuous abstinence at 24 weeks. RESULTS: 743 smokers, 43% male and 57% female, mean (SD) age: 41.9 (9.8) years. The continuous abstinence rate at 24 weeks was 37.3% (IC 95% 34.9-40.0).The multivariable model showed three variables with predictive value: no current psychiatric diagnosis, social support and the first item of Fagerström test (time to first cigarette in the morning). CONCLUSIONS: Treatment outcomes of this smoking cessation program was influenced by the following variables: nicotine dependence, psychiatric disorders and social support.