Melatonin concentration as a marker of the circadian phase in patients with obstructive sleep apnoea.

OBJECTIVE: The effects of obstructive sleep apnoea (OSA) on the markers of glucose metabolism and other hormones are of interest, particularly since there is growing evidence that OSA may be a risk factor for disorders such as insulin resistance. However, interpreting these studies depends on the target hormone not having a diurnal rhythm and the circadian rhythm not being altered by the sleep fragmentation that occurs in OSA. Therefore, the aim of our study was to test the hypothesis that OSA displaces the circadian rhythm. METHODS: We carried out a prospective, observational, controlled, parallel study in 22 OSA patients (mean [SD] age: 45.1 [8.8]years; apnoea/hypopnoea index (AHI): 37 [24] events/h) and 22 age matched healthy subjects (age: 47.9 [7.9]years; AHI: 3 [1] events/h). Saliva samples for the measurement of melatonin were collected from participants resting in dim light at 30 min intervals between 19:30 and 22:30 h. Dim light melatonin onset (DLMO), a marker of the circadian phase, was taken at the end of the 30 min interval in which the greatest rise in melatonin occurred. RESULTS: The group median (interquartile range) DLMO did not differ in OSA patients compared to healthy subjects (OSA patients: 90 [60-150]min; healthy subjects: 135 [90-150]min, p=0.19). CONCLUSION: The circadian phase is the same in OSA patients and healthy subjects using salivary melatonin concentration as a marker of the circadian phase.

Lack of association between impaired glucose tolerance and appetite regulating hormones in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghrelin, neuropeptide Y [NPY] and peptide tyrosine-tyrosine [PYY]). METHOD: We studied 68 OSA patients (mean AHI 22 events/h) and 37 age and weight matched healthy controls recruited by advertisement. All participants received a standardized evening meal, attended polysomnography and an oral glucose tolerance test (OGTT) on waking. Hormones were measured in blood taken before sleep (22:30) and at the start of the OGTT. RESULTS: Impaired glucose tolerance was present in 54% of patients and 32% of controls (p = 0.05). The only differences between groups was that leptin was significantly higher at 22:30 in OSA patients compared to controls (9.6 ng/L vs 7.9 ng/L, p = 0.05). OSA patients had marginally elevated plasma NPY levels at 22:30 (56.6 [52, 67] pmol/L vs 51.1[47.3, 61] pmol/L; p = 0.04). No differences in ghrelin, PYY or NPY were observed between patients with IGT and those without. However OSA patients with IGT had significantly higher value of leptin at both 22:30 (10.9 [7.7, 15.9] ng/mL vs 7.4 [5.6, 12.3] ng/mL, p = 0.02) and 07:00 (11.6 [7.6, 16.2] ng/mL vs 6.9 [5.4, 12.6] ng/mL, p = 0.024) than those without. In multivariate analysis the only major association of leptin was body mass index. CONCLUSION: Clinically significant abnormalities of appetite regulating hormones are not present in OSA. Appetite regulating hormones did not differ in OSA patients with and without impaired glucose tolerance.

Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory.

RATIONALE: Although cognitive deficits are well documented in patients with sleep apnea, the impact on memory remains unclear. OBJECTIVES: To test the hypotheses that (1) patients with obstructive sleep apnea have memory impairment and (2) memory impairment is commensurate with disease severity. METHODS: Patients with obstructive sleep apnea and healthy volunteers (apnea-hypopnea index <5 events/h) completed a test battery specially designed to differentiate between aspects of memory (semantic, episodic, and working) versus attention. Sleepiness was measured on the basis of the Epworth Sleepiness Scale and Oxford Sleep Resistance test. Memory performance in patients versus control subjects was compared (Mann-Whitney U test; P < 0.01, Bonferroni corrected for multiple comparisons) and relationships between performance and disease severity were analyzed by linear regression. MEASUREMENTS AND MAIN RESULTS: Sixty patients and healthy control subjects matched for age (mean +/- SD: patients, 51 +/- 9 yr; control subjects, 50 +/- 9 yr) and education (patients, 14 +/- 3 yr; control subjects, 15 +/- 3 yr) participated. Patients demonstrated impaired Logical Memory Test results (immediate recall: patients, median [range], 36 [9-69]; control subjects, 43 [19-64], P = 0.0004; and delayed recall: patients, 22 [6-42]; control subjects, 27 [10-46]; P = 0.0001). There were minimal differences in attention, visual episodic, semantic, or working memory; patients performed better than control subjects on Spatial Span forward and backward. Regression analysis revealed that Logical Memory Test performance was not significantly related to disease severity after controlling for age, education, and sleepiness. CONCLUSIONS: Obstructive sleep apnea is associated with impairment in verbal, but not visual, memory. The impairment was present across a range of disease severity and was not explained by reduced attention. Such verbal memory impairment may affect daytime functioning and performance.

Sleep architecture and attenuated heart rate response to arousal from sleep in patients with autonomic failure.

OBJECTIVE: To determine if patients with autonomic failure have increased sleep disturbances and if multiple system atrophy (MSA) and pure autonomic failure (PAF) patients have frequent arousals from sleep associated with an attenuated heart rate (HR) response compared to healthy volunteers. METHODS: With informed consent, 10 autonomic failure patients and 10 healthy volunteers were studied. Sleep disturbances were scored using standard criteria. Arousals were identified from stage 2 sleep and differences in the R-R interval between groups were tested using a mixed-model regression analysis. RESULTS: Three MSA and one PAF patient had obstructive sleep apnoea compared to one volunteer. One MSA and three PAF patients had periodic limb movements. One MSA patient had REM behaviour disorder. The autonomic patients had significantly reduced total sleep time (p=0.007) and sleep efficiency (p=0.003). The HR response to arousal was smaller in autonomic failure patients compared to volunteers during the early phase of the arousal (p=0.047), but not the later phase (p=0.67). CONCLUSION: Autonomic failure patients have increased sleep disturbances compared to healthy volunteers. The smaller HR response in autonomic failure patients suggests that an intact sympathetic nervous system is a key component of the HR response associated with arousal from sleep.