Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea-hypnoea index (AHI).

INTRODUCTION: Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure (CPAP), the conventional treatment for OSA, can be poor and considering weight loss is the most effective treatment for OSA. This trial examines whether the glucagon-like peptide-1 receptor agonist liraglutide, a glucose-lowering therapy associated with significant weight loss used in T2DM, can improve the severity and symptoms of OSA. METHODS AND ANALYSIS: This is an outpatient, single-centred, open-labelled, prospective, phase IV randomised controlled trial in a two-by-two factorial design. One hundred and thirty-two patients with newly diagnosed OSA (apnoea-hypopnoea index (AHI) ≥15 events/hour), and existing obesity and T2DM (glycated haemoglobin (HbA1c) ≥47 mmol/mol), will be recruited from diabetes and sleep medicine outpatient clinics in primary and secondary care settings across Liverpool. Patients will be allocated equally, using computer-generated random, permuted blocks of unequal sizes, to each of the four treatment arms for 26 weeks: (i) liraglutide (1.8 mg once per day) alone, (ii) liraglutide 1.8 mg once per day with CPAP, (iii) CPAP alone (conventional care) or (iv) no treatment (control). The primary outcome measure is change in OSA severity, determined by AHI. Secondary outcome measures include effects on glycaemic control (glycated haemoglobin (HbA1c)), body weight and quality of life measures. Exploratory measures include measures of physical activity, MRI-derived measures of regional body composition including fat mass (abdominal subcutaneous, visceral, neck and liver fat) and skeletal muscle mass (cross-sectional analysis of thigh), indices of cardiac function (using transthoracic echocardiography) and endothelial function. ETHICAL APPROVAL: The study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1019) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBERS: ISRCTN16250774. EUDRACT No. 2014-000988-41. UTN U1111-1139-0677.

Pulse transit time changes in subjects exhibiting sleep disordered breathing.

INTRODUCTION: Pulse Transit Time (PTT) represents a non-invasive marker of sleep fragmentation in OSAS. Little is known regarding PTT in sleepy subjects exhibiting nocturnal Inspiratory Flow Limitation (IFL) in the absence of apneas or desaturation. MATERIALS AND METHODS: The IFL cohort was gender and age matched to subjects with OSAS and a cohort where Sleep Disordered Breathing (SBD)/IFL was absent ("Non Flow Limited" or NFL cohort); PTT Arousal index (PTT Ar) defined by number of PTT arousals per hour. RESULTS: 20 subjects meeting criteria for the IFL cohort were aged and gender matched with OSAS and "NFL" subjects. Females comprised 65% of the IFL cohort; the mean BMI of the IFL cohort was significantly higher than the NFL cohort (34.25 v 28.90; p = 0.016) but not when compared to the OSAS cohort (34.25 v 36.31; p = 0.30). The PTT Ar in the IFL cohort (33.67 h) was significantly higher than the NFL cohort (23.89 h) but significantly lower than the OSAS cohort (55.21 h; F = 8.76; p < 0.001). PTT Ar was found to positively correlate with AHI (CC = 0.46; p < 0.001), ODI (CC = 0.47; p < 0.001) and RDI (CC = 0.49; p < 0.001). Within the IFL cohort, PTT Ar positively correlated with age (CC = 0.501; p = 0.024) but not gender and BMI. CONCLUSION: The PTT Arousal Index increased proportionately with severity of SDB with significantly higher markers of arousal in sleepy subjects exhibiting nocturnal IFL when compared to controls. Subjects exhibiting IFL were predominantly female with an elevated BMI. IFL may thus represent a significant pathogenic entity in the development of daytime sleepiness.

Sleep profiles and mood states during an expedition to the South Pole.

OBJECTIVE: To study sleep parameters and mood profiles of a female explorer traveling solo and unaided to the South Pole during the winter. METHODS: During the 44-day expedition, global activity and sleep were assessed using a wrist actigraph (AW) worn on the nondominant wrist. Mood was assessed using an adapted Profile of Mood States questionnaire. Pre- and post expedition physiologic profiles were conducted to assess body composition, strength and power, and aerobic capacity. RESULTS: The AW data revealed decreasing sleep duration throughout the expedition, with an average sleep time of 5 hours (range, 8 hours and 14 minutes to 1 hour and 42 minutes), with sleep times consistently <3 hours during the final third of the expedition. Mood responses indicated a progressive reduction in vigor and increase in fatigue. Sleep time was positively related to vigor and inversely related to depression and fatigue, a finding that is consistent with the notion that positive feelings (high vigor and low fatigue) are linked with sleep. CONCLUSIONS: This account provides insight to help understand the limits of human tolerance and may be directly applicable when planning future expeditions of this nature.

Acute sleep responses in a normobaric hypoxic tent.

PURPOSE: Sleeping in a hypoxic environment is becoming increasingly popular among athletes attempting to simulate a "live high, train low" training regime. The purpose of this study was to investigate the acute effects (one night) of sleeping in a normobaric hypoxic tent (NH) (PO(2) = 110 mm Hg approximately 2500 m) upon markers of sleep physiology and quality, compared with sleep in a normal ambient environment (BL) (PO(2) = 159 mm Hg approximately sea level) and sleep in a normobaric normoxic tent (NN) (PO(2) = 159 mm Hg). METHODS: Eight male recreational athletes (age 34.5 +/- 6.9 yr; stature 169.1 +/- 8.7 cm; mass 69.3 +/- 8.2 kg; VO(2max) 56.4 +/- 8.3 mL.kg(-1).min(-1)) participated in the study using a randomized, double-blind crossover design. Polysomnographic studies were undertaken to measure sleep stages, arterial oxygen saturation (SpO(2)), heart rate (HR), and the Respiratory Disturbance Index (RDI). The Leeds Sleep Evaluation Questionnaire (LSEQ) was used to measure subjective sleep quality. RESULTS: NH (89.9 +/- 4.8%) resulted in a significantly lower (P < 0.05) SpO(2) compared with both BL (95.7 +/- 1.5%) and NN (93.5 +/- 4.0%). Heart rate was significantly higher (P < 0.05) in NH (51.5 +/- 7.6 beats.min(-1)) compared with NN (48.3 +/- 6.9 beats.min(-1)) but was similar versus BL (50.3 +/- 4.3 beats.min(-1)). RDI (counts.h) and RDI (total counts) were lowest in BL (3.5 +/- 2.5; 18.1 +/- 7.9) and highest in NH (36.8 +/- 42.7; 221.9 +/- 254.5). The difference in RDI (counts.h(-1) and total counts) between NH and BL was significant (P < 0.05). The LSEQ revealed that subjects' "behavior following waking" score was significantly (P < 0.05) lower in NH (40.9 +/- 9.2) compared with BL (52.3 +/- 8.3). CONCLUSION: This study presents evidence that sleep in a normobaric hypoxic tent at a simulated altitude of 2500 m may affect sleep parameters in some individuals. This type of analysis may be useful in the early identification of poorly responding individuals to simulated altitude environments.

Symptomatic gastroesophageal reflux in subjects with a breathing sleep disorder.

STUDY OBJECTIVES: A link between gastroesophageal reflux (GER) and obstructive sleep apnea (OSA) has been suggested; however, the prevalence and frequency of symptomatic GER and the influence of OSA severity on GER are not known. DESIGN AND PATIENTS: Two hundred seventy-one subjects referred for overnight sleep studies were investigated for subjects with a breathing sleep disorder, occurrence of symptomatic GER, potential risk factors for both conditions, and comorbidity using a validated questionnaire. RESULTS: Overall, 160 of the 228 respondents (73%; 135 subjects with OSA and 93 subjects who snore) reported GER-related symptoms, with heartburn and/or acid regurgitation being the leading symptoms. No evidence of a difference in the occurrence of symptomatic GER between subjects who snore and subjects with OSA was observed (odds ratio [OR], 1.21; 95% confidence interval [CI], 0.7 to 2.1). Furthermore, the occurrence of reflux symptoms was not influenced by the severity of OSA (OR per 10 4% arterial oxygen saturation [SaO(2)] dips per hour, 0.98; 95% CI, 0.8 to 1.1). Self-reported comorbidity was higher in subjects with OSA compared with subjects who snore (p = 0.02), but none of the potential risks produced an association with the presence of reflux symptoms in this sample of patients with a breathing sleep disorder. CONCLUSION: We conclude that symptomatic GER is common in subjects with a breathing sleep disorder, but there was no difference between those with OSA and subjects who snore.