Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA) axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB) display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment

Neuroendocrine Alterations in Obese Patients with Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant morbidity and mortality when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. Obese patients with OSAS show a reduction of both spontaneous and stimulated growth hormone (GH) secretion coupled to reduced insulin-like growth factor-I (IGF-I) concentrations and impaired peripheral sensitivity to GH. Hypoxemia and chronic sleep fragmentation could affect the sleep-entrained prolactin (PRL) rhythm. A disrupted Hypothalamus-Pituitary-Adrenal (HPA) axis activity has been described in OSAS. Some derangement in Thyroid-Stimulating Hormone (TSH) secretion has been demonstrated by some authors, whereas a normal thyroid activity has been described by others. Changes of gonadal axis are common in patients with OSAS, who frequently show a hypogonadotropic hypogonadism. Altogether, hormonal abnormalities may be considered as adaptive changes which indicate how a local upper airway dysfunction induces systemic consequences. The understanding of the complex interactions between hormones and OSAS may allow a multi-disciplinary approach to obese patients with this disturbance and lead to an effective management that improves quality of life and prevents associated morbidity or death

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Role of sleep duration in the regulation of glucose metabolism and appetite.

Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regulates the appetite-stimulating hormone ghrelin, and increases hunger and food intake. Taken together with the epidemiologic evidence for an association between short sleep and the prevalence or incidence of diabetes mellitus and/or obesity, these results support a role for reduced sleep duration in the current epidemic of these metabolic disorders. Screening for habitual sleep patterns in patients with "diabesity" is therefore of great importance. Studies are warranted to investigate the putative therapeutic impact of extending sleep in habitual short sleepers with metabolic disorders.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Reviewinfo:eu-repo/semantics/publishe

Effect of sleep loss on the hypothalamo-pituitary-adrenal (HPA) axis

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Impact of short-term sleep restriction on glucose homeostasis

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Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation

The hypothalamus-pituitary-adrenal (HPA) axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting at the hypothalamic and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues (GHS)/GHS-receptor systems have been shown to exert a clear inhibitory and stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP), a GABA-A receptor agonist, shows the most marked inhibitory effect on both spontaneous and stimulated HPA axis activity, in agreement with its peculiar efficacy in panic disorders and depression where an HPA axis hyperactivation is generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol-releasing effect in humans and the ghrelin/GHS-R system is probably involved in the modulation of the HPA response to stress and nutritional/metabolic variations. The glucocorticoid-mediated negative feedback action is mediated by both glucocorticoid (GR) and mineralocorticoid (MR) receptors activation at the central level, mainly in the hippocampus. In agreement with animal studies, MRs seem to play a crucial role in the maintenance of the circadian ACTH and cortisol rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly ALP), ghrelin, as well as MR agonists/antagonists, may represent good tools to explore the activity of the HPA axis in both physiological conditions and pathological states characterized by an impaired control of the corticotroph function

Impact of obstructive sleep apnea on HDL levels in obesity

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Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men.

Context: Insufficient sleep is associated with increased cardio-metabolic risk. Alterations in hypothalamic-pituitary-adrenal (HPA) axis may underlie this link. Objective: To examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations. Methods: Thirteen subjects participated in 2 laboratory sessions (2 nights of 10h in bed versus 2 nights of 4h in bed) in a randomized cross-over design. Sleep was polygraphicallyrecorded. After the second night of each session, blood was sampled at 20-min intervals from 09:00 to 24:00 to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 14:00 to 24:00 to measure free cortisol. Perceived stress, hunger and appetite were assessed at hourly intervals by validated scales. Results: Sleep restriction was associated with a 19% increase in overall ACTH levels (p<0.03) that was correlated with the individual amount of sleep loss (rSp=0.63, p<0.02). Overall total cortisol levels were also elevated (+21%; p=0.10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (p<0.04), without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by respectively, 30% (p<0.03) and 200% (p<0.04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; p<0.05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol. Conclusion: The impact of sleep loss on HPA activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe