Correlation between breakfast tryptophan content and morning-evening in Japanese infants and students aged 0-15 yrs

Tryptophan can be metabolized via 5-hydroxytryptamine=serotonin to melatonin by a series of 4 enzymes in pineal body. Lack of serotonin in body fluid in the brain during daytime can lead to several psychiatric disorders, while shortage of plasma-melatonin at night can be related to sleep disorders. The Morning-Evening (M-E) questionnaire and the original questionnaire including questions on sleep habits, mental symptoms, and contents of meals were administered to 1055 infants aged 0-6 yrs, 751 students attending an elementary school, and 473 students attending junior high school in Kochi City (33 degrees N). The index of tryptophan taken at breakfast (Trp-Index) was calculated as tryptophan amount per one meal based on the tryptophan included in each 100 g of the foods and a standard amount of food per one meal. A significant positive-correlation between M-E scores and Trp-Index was not shown by relatively older students, aged 9-15 yrs (Pearson's test, r=0.044-0.123, p=0.071-0.505), whereas a significant positive correlation was shown by infants and young elementary school students aged 0-8 yrs (r=0.180, 0.258, p<0.001). The more frequently the infants had difficulty falling asleep at bedtime and waking up in the morning, the less the Trp-Indices taken at breakfast were (Kruskall-Wallis-test, p=0.027 for difficulty falling asleep; p=0.008 for difficulty waking up). The more frequently infants became angry even by a little trigger, or depressed, the lower (more evening-typed) the M-E scores were (Kruskal-Wallis test: p相似文献   

HYPERSENSITIVITY OF MELATONIN SUPPRESSION IN RESPONSE TO LIGHT IN PATIENTS WITH DELAYED SLEEP PHASE SYNDROME*

Patients with delayed sleep phase syndrome (DSPS) experiencea chronic mismatch between the usual daily schedule required by the individual'senvironment and their circadian sleep-wake pattern, resulting in major academic,work, and social problems. Although functional abnormalities of the circadianpacemaker system have been reported in patients with DSPS, the etiology ofDSPS has not been fully elucidated. One hypothesis proposed to explain whypatients with DSPS fail to synchronize their 24h sleep-wake cycle to theirenvironment is that they might have reduced sensitivity to environmental timecues, most notably light-dark cycles. Therefore, we compared the sensitivityof melatonin suppression in response to light in patients with DSPS and normalcontrol subjects. Fifteen patients with DSPS and age- and sex-matched healthycontrols were studied. As the melatonin secretion rhythm in patients withDSPS was expected to be delayed compared to the controls, the time of peakmelatonin secretion was determined in each subject in the first session. Inthe second session, each subject was exposed to light with an intensity of1000 lux for 2h beginning 2h prior to his or her peak melatonin secretion.Melatonin was measured by radioimmunoassay in saliva sampled every 30 minutesduring the period of light exposure. Suppression of the melatonin concentrationin saliva was dependent on duration of light exposure. In addition, the suppressiveeffect of light on the melatonin concentration was significantly greater inpatients with DSPS than in control subjects. The results suggest hypersensitivityto nighttime light exposure in patients with this syndrome. Our findings thereforesuggest that evening light restriction is important for preventing patientswith DSPS from developing a sleep phase delay. (ChronobiologyInternational, 18(2), 263–271, 2001)     

Melatonin rhythms in delayed sleep phase syndrome

The aim of this study was to compare circadian and sleep characteristics between patients with delayed sleep phase syndrome (DSPS) and healthy controls. The authors studied 8 DSPS patients and 15 normal controls. Serum melatonin concentration was assessed every hour for 24 h under dim light conditions. The sleep phase and the melatonin rhythm in DSPS patients were significantly delayed compared to those in normal controls. Sleep length was significantly greater in DSPS patients compared to that in controls, but the duration of melatonin secretion did not differ between the two groups. The final awakening, relative to melatonin onset, melatonin midpoint, and melatonin offset, was significantly longer in DSPS patients than in controls. By contrast, the timing of sleep onset relative to melatonin rhythm did not differ between the two groups. The authors found a significant positive correlation between sleep phase markers and melatonin phase markers in DSPS. They postulate that a delayed circadian pacemaker may be responsible for delayed sleep phase syndrome. The alteration of phase angle between melatonin rhythm and sleep phase suggested that not only the delay of the circadian clock but also a functional disturbance of the sleep-wake mechanism underlies DSPS.     

Hypersensitivity of melatonin suppression in response to light in patients with delayed sleep phase syndrome

Patients with delayed sleep phase syndrome (DSPS) experience a chronic mismatch between the usual daily schedule required by the individual's environment and their circadian sleep-wake pattern, resulting in major academic, work, and social problems. Although functional abnormalities of the circadian pacemaker system have been reported in patients with DSPS, the etiology of DSPS has not been fully elucidated. One hypothesis proposed to explain why patients with DSPS fail to synchronize their 24h sleep-wake cycle to their environment is that they might have reduced sensitivity to environmental time cues, most notably light-dark cycles. Therefore, we compared the sensitivity of melatonin suppression in response to light in patients with DSPS and normal control subjects. Fifteen patients with DSPS and age- and sex-matched healthy controls were studied. As the melatonin secretion rhythm in patients with DSPS was expected to be delayed compared to the controls, the time of peak melatonin secretion was determined in each subject in the first session. In the second session, each subject was exposed to light with an intensity of 1000 lux for 2h beginning 2h prior to his or her peak melatonin secretion. Melatonin was measured by radioimmunoassay in saliva sampled every 30 minutes during the period of light exposure. Suppression of the melatonin concentration in saliva was dependent on duration of light exposure. In addition, the suppressive effect of light on the melatonin concentration was significantly greater in patients with DSPS than in control subjects. The results suggest hypersensitivity to nighttime light exposure in patients with this syndrome. Our findings therefore suggest that evening light restriction is important for preventing patients with DSPS from developing a sleep phase delay. (Chronobiology International, 18(2), 263-271, 2001)     

Insomnia: zolpidem extended-release for the treatment of sleep induction and sleep maintenance symptoms

Insomnia impairs daytime functioning or causes clinically significant daytime distress. The consequences of insomnia, if left untreated, may contribute to the risks of developing additional serious conditions, such as psychiatric illness, cardiovascular disease, or metabolic issues. Furthermore, some comorbidities associated with insomnia may be bidirectional in their causality because psychiatric and other medical problems can increase the risk for insomnia. Regardless of the serious consequences of inadequately treated insomnia, clinicians often do not inquire into their patients' sleep habits, and patients, in turn, are not forthcoming with details of their sleep difficulties. The continuing education of physicians and patients with regard to insomnia and currently available therapies for the treatment of insomnia is, therefore, essential. Insomnia may present as either a difficulty falling asleep, difficulty maintaining sleep, or waking too early without being able to return to sleep. Furthermore, these symptoms often change over time in an unpredictable manner. Therefore, when considering a sleep medication, one with efficacy for the treatment of multiple insomnia symptoms is recommended. A modified-release formulation of zolpidem, zolpidem extended-release, has been approved for the treatment of insomnia characterized by both difficulty in falling asleep and maintaining sleep. Here, we review studies supporting the use of zolpidem extended-release in the treatment of sleep-onset and sleep maintenance difficulties.     

Melatonin Treatment Effects on Adolescent Students' Sleep Timing and Sleepiness in a Placebo-Controlled Crossover Study

During the last few decades, the incidence of sleep-onset insomnia, due to delay of circadian phase, has increased substantially among adolescents all over the world. We wanted to investigate whether a small dose of melatonin given daily, administered in the afternoon, could advance the sleep timing in teenagers. Twenty-one students, aged 14–19 yrs, with sleep-onset difficulties during school weeks were recruited. The study was a randomized, double blind, placebo (PL)-controlled crossover trial, lasting 5 wks. During the first 6 d in wks 2 and 4, the students received either PL or melatonin (1 mg) capsules between 16:30 and 18:00 h. During the first 6 d of wk 5, all students received melatonin. Wks 1 and 3 were capsule-free. In the last evening of each week and the following morning, the students produced saliva samples at home for later melatonin analysis. The samples were produced the same time each week, as late as possible in the evening and as early as possible in the morning. Both the student and one parent received automatic mobile text messages 15 min before saliva sampling times and capsule intake at agreed times. Diaries with registration of presumed sleep, subjective sleepiness during the day (Karolinska Sleepiness Scale, KSS) and times for capsule intake and saliva samplings were completed each day. Primary analysis over 5 wks gave significant results for melatonin, sleep and KSS. Post hoc analysis showed that reported sleep-onset times were advanced after melatonin school weeks compared with PL school weeks (p < .005) and that sleep length was longer (p < .05). After the last melatonin school week, the students fell asleep 68 min earlier and slept 62 min longer each night compared with the baseline week. Morning melatonin values in saliva diminished compared with PL (p < .001) and evening values increased (p < .001), indicating a possible sleep phase advance. Compared with PL school weeks, the students reported less wake up (p < .05), less school daytime sleepiness (p < .05) and increased evening sleepiness (p < .005) during melatonin weeks. We conclude that a small dose of melatonin given daily, administered in the afternoon, could advance the sleep timing and make the students more alert during school days even if they continued their often irregular sleep habits during weekends. (Author correspondence: arne.lowden@stress.su.se)     

Eveningness associates with smoking and sleep problems among pregnant women

Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness–eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep (OR = 3.4, p < 0.0001), poor sleep quality (OR = 2.9, p < 0.01) and daily tiredness (OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale (p < 0.05), Basic Nordic Sleep Questionnaire (p < 0.0001) and Global Seasonality Score (p < 0.01) and were also more often smokers, also during pregnancy (p < 0.001) and reported poorer general health (p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood (OR = 1.5, p < 0.05) and adolescence (OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.     

Can the circadian phase be estimated from self-reported sleep timing in patients with Delayed Sleep Wake Phase Disorder to guide timing of chronobiologic treatment?

Introduction: The efficacy of bright light and/or melatonin treatment for Delayed Sleep Wake Phase Disorder (DSWPD) is contingent upon an accurate clinical assessment of the circadian phase. However, the process of determining this circadian phase can be costly and is not yet readily available in the clinical setting. The present study investigated whether more cost-effective and convenient estimates of the circadian phase, such as self-reported sleep timing, can be used to predict the circadian phase and guide the timing of light and/or melatonin treatment (i.e. dim-light melatonin onset, core body temperature minimum and melatonin secretion mid-point) in a sample of individuals with DSWPD. Method: Twenty-four individuals (male = 17; mean age = 21.96, SD = 5.11) with DSWPD were selected on the basis of ICSD-3 criteria from a community-based sample. The first 24-hours of a longer 80-hour constant laboratory ultradian routine were used to determine core body temperature minimum (cBT^min), dim-light melatonin onset (DLMO) and the midpoint of the melatonin secretion period (DLM^mid = [DLM°^ff–DLMO]/2). Prior to the laboratory session subjective sleep timing was assessed using a 7-day sleep/wake diary, the Pittsburgh Sleep Quality Index (PSQI), and the Delayed Sleep Phase Disorder Sleep Timing Questionnaire (DSPD-STQ). Results: Significant moderate to strong positive correlations were observed between self-reported sleep timing variables and DLMO, cBT^min and DLM^mid. Regression equations revealed that the circadian phase (DLMO, cBT^min and DLM^mid) was estimated within ±1.5 hours of the measured circadian phase most accurately by the combination of sleep timing measures (88% of the sample) followed by sleep diary reported midsleep (83% of the sample) and sleep onset time (79% of the sample). Discussion: These findings suggest that self-reported sleep timing may be useful clinically to predict a therapeutically relevant circadian phase in DSWPD.     

A PEDIGREE OF ONE FAMILY WITH DELAYED SLEEP PHASE SYNDROME

The prevalence of delayed sleep phase syndrome (DSPS) has been estimated to be quite low. Although no genetic inheritance pattern has been described, it has been reported that close to 50% of DSPS patients have biological relatives with similar symptoms. A pedigree of one extended family with symptoms suggestive of DSPS has been identified. Morningnesseveningness questionnaires were administered to all first- and second-degree relatives of a proband identified with DSPS. A total of 51 (86%) questionnaires were returned, and 6 adult biological relatives of 27 (22%) showed a preference for eveningness, which is much higher than reported in the general population. Both the paternal and maternal branches contained affected individuals, suggesting the possibility of a bilineal mode of inheritance. While the trait did not obey simple Mendelian inheritance, the vertical patterns of transmission were consistent with either an autosomal dominant mode of inheritance with incomplete penetrance or a multifactorial mode of inheritance. These data provide some preliminary support to the notion that eveningness, and thus DSPS, may have a genetic component. The prevalence of symptoms suggestive of DSPS is higher in this family than reported in the general population. Case reports such as this support the utility of larger, more systematic studies. It is unclear whether this degree of familiarity is representative of that in the general population. (Chronobiology International, 18(5), 831–840, 2001)     

Sleep Parameters among Offshore Workers: An Initial Assessment in the Campos Basin,Rio De Janeiro,Brazil

Shift work has potentially adverse effects on health, particularly on sleep. The purpose of the present study was to assess sleep parameters among personnel working in oil and gas offshore installations in the Campos Basin, Rio de Janeiro, Brazil. One hundred and seventy-nine subjects were asked to complete a sleep questionnaire with multiple-choice answers. Offshore workers were divided into two groups according to their work schedule: (1) fixed daytime workers (n = 86; age: 35.8 ± 9.6 yrs) and (2) shift (n = 87) or night (n = 6) workers (total n = 93; age: 37.7 ± 9.7 yrs). Shift/night workers reported poor sleep more frequently than the daytime workers (20.4% vs. 1.2%, p < 0.01), as well as habitual difficulty in falling asleep (15.1% vs. 4.7%, p < 0.01), long latency of sleep onset (28% vs. 7%, p < 0.01), fragmented sleep (45.2% vs. 16.3%, p < 0.01), short sleep episodes (44.1% vs. 16.3%, p < 0.01), irregular bedtimes (29.0% vs. 12.8%, p < 0.01), and feeling tired upon awakening (15.1% vs. 3.5%, p < 0.01). Habitual napping and loud snoring were reported twice as often in shift/night than in day workers (p < 0.01). Nightmares, somnambulism, and unpleasant feeling in the legs were equality reported by both groups (p > 0.05). Few offshore workers had sought medical help for their sleep problems. A higher number of shift/night workers reported feelings of sadness compared with day workers (26.9% vs. 9.3%, p < 0.01). The findings of this study show that subjective reports of sleep-related problems are quite common among Brazilian offshore shift workers. Reliance on self-reported sleep problems and a cross-sectional design are the main limitations of our study.     

Bright-light mask treatment of delayed sleep phase syndrome

We treated delayed sleep phase syndrome (DSPS) with an illuminated mask that provides light through closed eyelids during sleep. Volunteers received either bright white light (2,700 lux, n = 28) or dim red light placebo (0.1 lux, n = 26) for 26 days at home. Mask lights were turned on (< 0.01 lux) 4 h before arising, ramped up for 1 h, and remained on at full brightness until arising. Volunteers also attempted to systematically advance sleep time, avoid naps, and avoid evening bright light. The light mask was well tolerated and produced little sleep disturbance. The acrophase of urinary 6-sulphatoxymelatonin (6-SMT) excretion advanced significantly from baseline in the bright group (p < 0.0006) and not in the dim group, but final phases were not significantly earlier in the bright group (ANCOVA ns). Bright treatment did produce significantly earlier phases, however, among volunteers whose baseline 6-SMT acrophase was later than the median of 0602 h (bright shift: 0732-0554 h, p < 0.0009; dim shift: 0746-0717 h, ns; ANCOVA p = 0.03). In this subgroup, sleep onset advanced significantly only with bright but not dim treatment (sleep onset shift: bright 0306-0145 h, p < 0.0002; dim 0229-0211 h, ns; ANCOVA p < .05). Despite equal expectations at baseline, participants rated bright treatment as more effective than dim treatment (p < 0.04). We conclude that bright-light mask treatment advances circadian phase and provides clinical benefit in DSPS individuals whose initial circadian delay is relatively severe.     

SLEEP AND SLEEPINESS: IMPACT OF ENTERING OR LEAVING SHIFTWORK—A PROSPECTIVE STUDY

Very little is known about the effects on sleep and sleepiness of entering or exiting shiftwork. The present study used a longitudinal database (n?=?3637). Participants completed a questionnaire on work hours, sleep, and work environment at the start and end of a 5-yr period. Changes in shift/day work status were related to change in a number of subjective sleep variables using logistic regression analysis. The analyses were adjusted for age, sex, and differences in socioeconomic status, work demands, work control, physical workload, marriage status, and number of children. In comparison with constant day work, entering shiftwork (with or without night shifts) from day work increased the risk of difficulties in falling asleep, and leaving shiftwork reduced this risk (odds ratio [OR]?=?2.8 [confidence interval, CI?=?1.8–4.5]). Also falling asleep at work showed a consistent pattern; an increased risk of falling asleep for those with shiftwork on both occasions, and for those with night work on both occasions. Also entering night work was associated with a strongly increased risk of falling asleep at work (OR?=?2.9 [CI?=?1.3–6.7]). These results suggest that entering and leaving shiftwork has a considerable impact on sleep and alertness. However, there is a need for large and more extended longitudinal studies to support our findings. (Author correspondence: Torbjorn.akerstedt@ki.se)     

Propofol-Induced Sleep: Efficacy and Safety in Patients with Refractory Chronic Primary Insomnia

Insomnia, defined as difficulty in falling asleep and/or staying asleep, short sleep duration, or poor quality sleep, is a common sleep disorder affecting 30-40% of adult population. We have conducted a randomized, double-blind, placebo-controlled study to test if anesthesia is therapeutically beneficial in patients with refractory chronic primary insomnia. We have assessed the efficacy and safety of propofol-induced sleep in these patients. This study comprised of 103 patients with refractory chronic primary insomnia (including 59 non-pregnant, non-lactating women; 28-60 years) and the participants were randomized to receive either physiological saline (placebo) (n = 39) or 3.0 g/l propofol (n = 64) in a 2-h continuous intravenous infusion for five consecutive nights. The Leeds Sleep Evaluation Questionnaire was used for the subjective assessment of sleep, and polysomnography was used for the objective measurement of sleep architecture and patterns. The assessments were done prior to and at the end of the 5-day treatment and 6 months after treatment period. The adverse effects of the treatment were also recorded. A 2-h continuous intravenous infusion of 3.0 g/l propofol for five consecutive nights improved the subjective and objective assessments of sleep in 64 patients with refractory chronic primary insomnia. This improvement occurred immediately after the therapy and persisted for 6 months. No serious adverse events were noticed during the period of drug administration or 6 months after the treatment. Propofol therapy is an efficacious and safe choice for restoring normal sleep in patients with refractory chronic primary insomnia.     

Daily Rhythms of Toxicity and Effectiveness of Anesthetics (MS222 and Eugenol) in Zebrafish (Danio Rerio)

Sleep inertia is a brief period of inferior task performance and/or disori-entation immediately after sudden awakening from sleep. Normally sleep inertia lasts <5 min and has no serious impact on conducting routine jobs. This preliminary study examined whether there are best and worst times to wake up stemming from circadian effects on sleep inertia. Since the process of falling asleep is strongly influenced by circadian time, the reverse process of awakening could be similarly affected. A group of nine subjects stayed awake for a 64-h continuous work period, except for 20-min sleep periods (naps) every 6 h. Another group of 10 subjects stayed awake for 64 h without any sleep. The differences between these two groups in performance degradation are expected to show sleep inertia on the background of sleep deprivation. Sleep inertia was measured with Baddeley's logical reasoning task, which started within 1 min of awakening and lasted for 5 min. There appeared to be no specific circadian time when sleep inertia is either maximal or minimal. An extreme form of sleep inertia was observed, when the process of waking up during the period of the circadian body temperature trough became so traumatic that it created “sleep (nap) aversion.” The findings lead to the conclusion that there are no advantages realized on sleep inertia by waking up from sleep at specific times of day.     

Chronotype in very low birth weight adults – a sibling study

ABSTRACT

Chronotype is the temporal preference for activity and sleep during the 24 h day and is linked to mental and physical health, quality of life, and mortality. Later chronotypes, so-called “night owls”, consistently display poorer health outcomes than “larks”. Previous studies have suggested that preterm birth (<37 weeks of gestation) is associated with an earlier chronotype in children, adolescents, and young adults, but studies beyond this age are absent. Our aim was to determine if adults born preterm at very low birth weight (VLBW, ≤1500 g) display different chronotypes than their siblings. We studied VLBW adults, aged 29.9 years (SD 2.8), matched with same-sex term-born siblings as controls. A total of 123 participants, consisting of 53 sibling pairs and 17 unmatched participants, provided actigraphy-derived data on the timing, duration, and quality of sleep from 1640 nights (mean 13.3 per participant, SD 2.7). Mixed effects models provided estimates and significance tests. Compared to their siblings, VLBW adults displayed 27 min earlier sleep midpoint during free days (95% CI: 3 to 51 min, p =.029). This was also reflected in the timing of falling asleep, waking up, and sleep-debt corrected sleep midpoint. The findings were emphasized in VLBW participants born small for gestational age. VLBW adults displayed an earlier chronotype than their siblings still at age 30, which suggests that the earlier chronotype is an enduring individual trait not explained by shared family factors. This preference could provide protection from risks associated with preterm birth.     

Clock Polymorphisms and Circadian Rhythms Phenotypes in a Sample of the Brazilian Population

A Clock polymorphism T to C situated in the 3′ untranslated region (3′‐UTR) has been associated with human diurnal preference. At first, Clock 3111C had been reported as a marker for evening preference. However these data are controversial, and data both corroborating and denying them have been reported. This study hypothesizes that differences in Clock genotypes could be observed if extreme morning‐type subjects were compared with extreme evening‐type subjects, and the T3111C and T257G polymorphisms were studied. The possible relationship between both polymorphisms and delayed sleep phase syndrome (DSPS) was also investigated. An interesting and almost complete linkage disequilibrium between the polymorphisms T257G in the 5′ UTR region and the T3111C in the 3′ UTR region of the Clock gene is described. Almost always, a G in position 257 corresponds to a C in position 3111, and a T in position 257 corresponds to a T in position 3111. The possibility of an interaction of these two regions in the Clock messenger RNA structure that could affect gene expression was analyzed using computer software. The analyses did not reveal an interaction between those two regions, and it is unlikely that this full allele correspondence affects Clock gene expression. These results show that there is no association between either polymorphism T3111C or T257G in the Clock gene with diurnal preference or delayed sleep phase syndrome (DSPS). These controversial data could result from the possible effects of latitude and clock genes interaction on circadian phenotypes.     

A prospective study of delayed sleep phase syndrome in patients with severe resistant obsessive-compulsive disorder

There have been relatively few studies examining sleep in patients with obsessive-compulsive disorder (OCD) and these have produced contradictory findings. A recent retrospective study identified a possible association between OCD and a circadian rhythm sleep disorder known as delayed sleep phase syndrome (DSPS). Patients with this pattern of sleeping go to bed and get up much later than normal. They are unable to shift their sleep to an earlier time and, as a result, suffer considerable disruption to social and occupational functioning. In this study, we examined the sleep of patients with OCD prospectively. We aimed to establish the frequency of DSPS in this population and any associated clinical or demographic factors which might be implicated in its aetiology.     

Associations between nocturnal urinary 6-sulfatoxymelatonin,obstructive sleep apnea severity and glycemic control in type 2 diabetes

Reduced nocturnal secretion of melatonin, a pineal hormone under circadian control, and obstructive sleep apnea have been both identified as risk factors for the development of type 2 diabetes mellitus. Whether they interact to impact glycemic control in patients with existing type 2 diabetes is not known. Therefore, this study explores the relationships between obstructive sleep apnea, melatonin and glycemic control in type 2 diabetes. As diabetic retinopathy may affect melatonin secretion, we also explore the relationship between retinopathy, melatonin and glycemic control. Fifty-six non-shift workers with type 2 diabetes, who were not using beta-blockers, participated. Most recent hemoglobin A1c (HbA1c) levels and the results of ophthalmologic examinations were obtained from medical records. Obstructive sleep apnea was diagnosed using an ambulatory device. Sleep duration and fragmentation were recorded by 7-day wrist actigraphy. The urinary 6-sulfatoxymelatonin/creatinine ratio, an indicator of nocturnal melatonin secretion, was measured in an overnight urine sample. Mediation analyses were applied to explore whether low nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio could be a causal link between increasing obstructive sleep apnea severity [as measured by an Apnea Hypopnea Index (AHI)] and poorer glycemic control, and between the presence of retinopathy and glycemic control. AHI and HbA1c were log-scale (ln) transformed. Obstructive sleep apnea was found in 76.8%, and 25.5% had diabetic retinopathy. The median (interquartile range) of urinary 6-sulfatoxymelatonin/creatinine ratio was 12.3 (6.0, 20.1) ng/mg. Higher lnHbA1c significantly correlated with lower 6-sulfatoxymelatonin/creatinine ratio (p = 0.04) but was not directly associated with OSA severity. More severe obstructive sleep apnea (lnAHI, p = 0.01), longer diabetes duration (p = 0.02), retinopathy (p = 0.01) and insulin use (p = 0.03) correlated with lower urinary 6-sulfatoxymelatonin/creatinine ratio, while habitual sleep duration and fragmentation did not. A mediation analysis revealed that lnAHI negatively correlated with urinary 6-sulfatoxymelatonin/creatinine ratio (coefficient = ?2.413, p = 0.03), and urinary 6-sulfatoxymelatonin/creatinine negatively associated with lnHbA1c (coefficient = ?0.005, p = 0.02), after adjusting for covariates. Mediation analysis indicated that the effect of lnAHI on lnHbA1c was indirectly mediated by urinary 6-sulfatoxymelatonin/creatinine ratio (B = 0.013, 95% CI: 0.0006, 0.0505). In addition, having retinopathy was significantly associated with reduced nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio, and an increase in HbA1c by 1.013% of its original value (B = ?0.013, 95% CI: ?0.038, ?0.005). In conclusion, the presence and severity of obstructive sleep apnea as well as the presence of diabetic retinopathy were associated with lower nocturnal melatonin secretion, with an indirect adverse effect on glycemic control. Intervention studies are needed to determine whether melatonin supplementation may be beneficial in type 2 diabetes patients with obstructive sleep apnea.     

Sleep Loss and Performance of Anaesthesia Trainees and Specialists

Fatigue risk associated with work schedules of hospital doctors is coming under increasing scrutiny, with much of the research and regulatory focus on trainees. However, provision of 24 h services involves both trainees and specialists, who have different but interdependent work patterns. This study examined work patterns, sleep (actigraphy, diaries) and performance (psychomotor vigilance task pre‐ and post‐duty) of 28 anaesthesia trainees and 20 specialists across a two‐week work cycle in two urban public hospitals. Trainees at one hospital worked back‐to‐back 12 h shifts, while the others usually worked 9 h day shifts but periodically worked a 14 h day (08:00–22:00 h) to maintain cover until arrival of the night shift (10 h). On 11% of day shifts and 23% of night shifts, trainees were working with ≥2 h of acute sleep loss. However, average sleep loss was not greater on night shifts, possibly because workload at night in one hospital often permitted some sleep. Post‐night shift performance was worse than post‐day shift performance for the median (t₍₁₃₁₎=3.57, p<0.001) and slowest 10% of reaction times (t₍₁₃₄₎=2.91, p<0.01). At the end of night shifts, poorer performance was associated with longer shift length, longer time since waking, greater acute sleep loss, and more total work in the past 24 h. Specialists at both hospitals had scheduled clinical duties during the day and were periodically scheduled on call to cover after‐hours services. On 8% of day shifts and 14% of day+call schedules, specialists were working with ≥2 h of acute sleep loss. They averaged 0.6 h less sleep when working day shifts (t_(23.5)=2.66, p=0.014) and 0.8 h less sleep when working day shifts+call schedules (t_(26.3)=2.65, p=0.013) than on days off. Post‐duty reaction times slowed linearly across consecutive duty days (median reaction time, t₍₁₃₁₎=?3.38, p<0.001; slowest 10%, t₍₁₆₀₎=?3.33, p<0.01; fastest 10%, t₍₁₃₈₎=?2.67, p<0.01). Poorer post‐duty performance was associated with greater acute sleep loss and longer time since waking, but better performance was associated with longer day shifts, consistent with circadian improvement in psychomotor performance across the waking day. This appears to be the first study to document sleep loss among specialist anaesthetists. Consistent with observations from experimental studies, the sleep loss of specialists across 12 consecutive working days was associated with a progressive decline in post‐duty PVT performance. However, this decline occurred with much less sleep restriction (< 1 h per day) than in laboratory studies, suggesting an exacerbating effect of extended wakefulness and/or cumulative fatigue associated with work demands. For both trainees and specialists, robust circadian variation in PVT performance was evident in this complex work setting, despite the potential confounds of variable shift durations and workloads. The relationship between PVT performance of an individual and the safe administration of anaesthesia in the operating theater is unknown. Nevertheless, the findings reinforce that any schedule changes to reduce work‐related fatigue need to consider circadian performance variation and the potential transfer of workload and fatigue risk between trainees and specialists.