Guidelines for the design and conduct of human clinical trials on ingestion-time differences - chronopharmacology and chronotherapy - of hypertension medications.

Current hypertension guidelines fail to provide a recommendation on when-to-treat, thus disregarding relevant circadian rhythms that regulate blood pressure (BP) level and 24 h patterning and medication pharmacokinetics and pharmacodynamics. The ideal purpose of ingestion-time (chronopharmacology, i.e. biological rhythm-dependent effects on the kinetics and dynamics of medications, and chronotherapy, i.e. the timing of pharmaceutical and other treatments to optimize efficacy and safety) trials should be to explore the potential impact of endogenous circadian rhythms on the effects of medications. Such investigations and outcome trials mandate adherence to the basic standards of human chronobiology research. In-depth review of the more than 150 human hypertension pharmacology and therapeutic trials published since 1974 that address the differential impact of upon-waking/morning versus at-bedtime/evening schedule of treatment reveals diverse protocols of sometimes suboptimal or defective design and conduct. Many have been "time-of-day," i.e. morning versus evening, rather than circadian-time-based, and some relied on wake-time office BP rather than around-the-clock ambulatory BP measurements (ABPM). Additionally, most past studies have been of too small sample size and thus statistically underpowered. As of yet, there has been no consensual agreement on the proper design, methods and conduct of such trials. This Position Statement recommends ingestion-time hypertension trials to follow minimum guidelines: (i) Recruitment of participants should be restricted to hypertensive individuals diagnosed according to ABPM diagnostic thresholds and of a comparable activity/sleep routine. (ii) Tested treatment-times should be selected according to internal biological time, expressed by the awakening and bed times of the sleep/wake cycle. (iii) ABPM should be the primary or sole method of BP assessment. (iv) The minimum-required features for analysis of the ABPM-determined 24 h BP pattern ought to be the asleep (not "nighttime") BP mean and sleep-time relative BP decline, calculated in reference to the activity/rest cycle per individual. (v) ABPM-obtained BP means should be derived by the so-called adjusted calculation procedure, not by inaccurate arithmetic averages. (vi) ABPM should be performed with validated and calibrated devices at least hourly throughout two or more consecutive 24 h periods (48 h in total) to achieve the highest reproducibility of mean wake-time, sleep-time and 48 h BP values plus the reliable classification of dipping status. (vii) Calculation of minimum required sample size in adherence with proper statistical methods must be provided. (viii) Hypertension chronopharmacology and chronotherapy trials should preferably be randomized double-blind, randomized open-label with blinded-endpoint, or crossover in design, the latter with sufficient washout period between tested treatment-time regimens.

COVID-19 associated with diabetes and other noncommunicable diseases led to a global health crisis.

COVID-19 has gravely threatened high-risk populations, such as people with diabetes and other noncommunicable diseases, leading to disproportionate hospitalizations and deaths worldwide. It is well documented from previous outbreaks that diabetes increases the risk for poor outcomes due to SARS infection. In the present review, we bring evidence that the country and global level health crisis caused by COVID-19 could have been avoided or extremely minimized if measures to protect high-risk populations were implemented timely. In addition to general lockdowns, testing, tracing, isolation and hygiene measures, other specific interventions for diabetes and comorbidities management were shown crucial to allow the continuation of care services during the pandemic. These interventions included: teleconsultation, digital remote education andmonitoring, e-prescriptions, medicine delivery options, mobile clinics, and home point-of-care tests. In conclusion, we recommend prompt actions to protect the most vulnerable groups, valuing knowledge and experiences from previous outbreaks and lessons learned during the COVID-19 pandemic, in order to shield communities, health systems and the global economy.

Sleep-wake cycle impairment adding on the risk for COVID-19 severity in people with diabetes.

In the present article, we explore the risks of circadian disruptions and impact on the sleep-wake cycle of individuals with diabetes during COVID-19 pandemic. The association between the duration and quality of sleep and the stability of glucose levels is well-established. Therefore, during the pandemic with changes and limitations in the exposure to cyclic cues that entrain the circadian rhythms, such as light-dark and social interactions, we hypothesize that the power and stability of circadian rhythms decrease if measures are not taken to intentionally create a routine that includes zeitgebers. Knowing that sleep-wake cycle disruptions impair melatonin production, immune system response and glucose metabolism, and that individuals with diabetes are at higher risk for poor prognosis when infected by SARS-CoV-2 (especially if their blood glucose is out of target), we recommend monitoring and advising these individuals towards strategies to maintain adequate sleep quality and duration as part of their preventive and protective measures during the new pandemic routine.

Afternoon School Start Times Are Associated with a Lack of Both Social Jetlag and Sleep Deprivation in Adolescents.

The delayed circadian timing of adolescents creates a conflict with early school start times (SSTs). We used wrist actimetry to compare sleep parameters and routine nighttime activities in middle school students attending either a morning (0700 to 1200 h) or an afternoon (1230 to 1730 h) school shift. On school days, students from both shifts (n = 21 for morning shift, n = 20 for afternoon shift, ages 12-14 years) had a similar sleep onset, but morning-shift students had an earlier sleep offset and a 1 h 45 min shorter sleep duration than their afternoon peers, who slept the recommended 8 to 10 h of daily sleep. Only morning-shift students had afternoon naps, but this afternoon sleep was not sufficient to overcome sleep deprivation. On weekends, sleep onsets and offsets did not differ between shifts. Because only morning-shift students woke up later and slept longer (2 h 3 min) on weekends, they were also the only ones who experienced social jetlag. Daily surveys on their nighttime (from 1800 to 0600 h) activities indicated there was no difference between shifts in the time spent on leisure or using electronic media during school days, but students from both shifts spent more time in these activities during the weekend. Our study confirms that early SST in adolescents is associated with sleep deprivation and suggests that schedules that start much later than typically considered may be needed to eliminate sleep deprivation in adolescents.

Depressive symptoms and chronotypes of elderly nursing home residentes: A case management study.

Institutionalization potentiates the tendency for specific sleep disturbances which occur with aging, besides negative health consequences such as increased rate of depressive symptoms. OBJECTIVE: To compare sleep profile and depressive symptoms in elderly nursing home residents, highlighting gender differences. METHODS: A quantitative descriptive study of 29 elderly from two different nursing homes was conducted. A sociodemographics questionnaire, Sleep Diary, Morningness-Eveningness Questionnaire and the 15-item Geriatric Depression Scale were applied. Data were analyzed using descriptive statistics, Student's t-test and the Mann-Whitney U-test. RESULTS: The sample comprised individuals that were predominantly female (72%), aged 80-90 years (48%), widowed (66%) and low-educated (83%). The women were found to sleep and awake later than the men. Regarding chronotypes, the women were classified as evening types and men as intermediate/indifferent types. Most of the elderly exhibited symptoms of major depression (48%). Compared to men, women had more depressive symptoms in both dysthymia and major depression categories. CONCLUSION: No significant differences were evident on comparisons of sleep profile and depressive symptoms, but elderly with the intermediate chronotype scored lower on the depressive symptoms scale.

A institucionalização potencializa a tendência às alterações específicas que ocorrem no sono com o envelhecimento, além de consequências negativas para a saúde como o aumento da prevalência de sintomas depressivos. OBJETIVO: Comparar o perfil do sono com os sintomas depressivos de idosos residentes em instituições de longa permanência para idosos. MÉTODOS: Trata-se um estudo descritivo e quantitativo, desenvolvido 29 com idosos residentes em duas diferentes Instituições de Longa Permanência para Idosos. Foram utilizados um questionário de informações sociodemográficas, Diário do Sono, Questionário para identificação de Indivíduos Matutinos e Vespertinos e Escala de Depressão Geriátrica versão de 15 itens. Os dados foram analisados por meio de uma estatística descrita, Teste t de Student e teste U de Mann-Whitney. RESULTADOS: Houve predomínio de mulheres (72%%), idade entre 80 a 90 anos (48%), viúvas (66%) e com baixa escolaridade (83%). Observou-se que as mulheres dormiram e acordaram mais tarde comparados aos homens. Quanto ao cronotipo, as mulheres foram classificadas como vespertino e os homens como intermediários/ indiferentes. A maioria dos idosos apresentou sintomas de depressão maior (48%), quando comparado aos homens, as mulheres manifestaram mais sintomas depressivos, tanto na categoria distimia quanto depressão maior. CONCLUSÃO: Conclui-se que não houve diferença significante nas comparações entre o perfil do sono e sintomas depressivos, porém os idosos com o cronotipo intermediário apresentaram menor escore na escala de sintomas depressivos.

Depressive symptoms and chronotypes of elderly nursing home residentes: A case management study / Sintomas depressivos e cronotipos de idosos residentes de instituições de longa permanência (ilpis): um estudo decorrente de gestão de casos

ABSTRACT. Institutionalization potentiates the tendency for specific sleep disturbances which occur with aging, besides negative health consequences such as increased rate of depressive symptoms. Objective: To compare sleep profile and depressive symptoms in elderly nursing home residents, highlighting gender differences. Methods: A quantitative descriptive study of 29 elderly from two different nursing homes was conducted. A sociodemographics questionnaire, Sleep Diary, Morningness-Eveningness Questionnaire and the 15-item Geriatric Depression Scale were applied. Data were analyzed using descriptive statistics, Student's t-test and the Mann-Whitney U-test. Results: The sample comprised individuals that were predominantly female (72%), aged 80-90 years (48%), widowed (66%) and low-educated (83%). The women were found to sleep and awake later than the men. Regarding chronotypes, the women were classified as evening types and men as intermediate/indifferent types. Most of the elderly exhibited symptoms of major depression (48%). Compared to men, women had more depressive symptoms in both dysthymia and major depression categories. Conclusion: No significant differences were evident on comparisons of sleep profile and depressive symptoms, but elderly with the intermediate chronotype scored lower on the depressive symptoms scale.

RESUMO. A institucionalização potencializa a tendência às alterações específicas que ocorrem no sono com o envelhecimento, além de consequências negativas para a saúde como o aumento da prevalência de sintomas depressivos. Objetivo: Comparar o perfil do sono com os sintomas depressivos de idosos residentes em instituições de longa permanência para idosos. Métodos: Trata-se um estudo descritivo e quantitativo, desenvolvido 29 com idosos residentes em duas diferentes Instituições de Longa Permanência para Idosos. Foram utilizados um questionário de informações sociodemográficas, Diário do Sono, Questionário para identificação de Indivíduos Matutinos e Vespertinos e Escala de Depressão Geriátrica versão de 15 itens. Os dados foram analisados por meio de uma estatística descrita, Teste t de Student e teste U de Mann-Whitney. Resultados: Houve predomínio de mulheres (72%%), idade entre 80 a 90 anos (48%), viúvas (66%) e com baixa escolaridade (83%). Observou-se que as mulheres dormiram e acordaram mais tarde comparados aos homens. Quanto ao cronotipo, as mulheres foram classificadas como vespertino e os homens como intermediários/ indiferentes. A maioria dos idosos apresentou sintomas de depressão maior (48%), quando comparado aos homens, as mulheres manifestaram mais sintomas depressivos, tanto na categoria distimia quanto depressão maior. Conclusão: Conclui-se que não houve diferença significante nas comparações entre o perfil do sono e sintomas depressivos, porém os idosos com o cronotipo intermediário apresentaram menor escore na escala de sintomas depressivos.

Peripheral body temperature impairment in individuals with type 1 diabetes mellitus.

OBJECTIVE: The aim of the present study was to evaluate the peripheral temperature rhythmicity and control in individuals with type 1 diabetes mellitus. METHODS: Twelve non-obese adults (20-40 years old) with type 1 diabetes mellitus (T1D) and eight control individuals, matched for age and BMI, wore a wrist temperature recorder for 10 consecutive days. Recorded data were aggregated to calculate M10 (ten hours of highest temperature) and L5 (five hours of lowest temperature) of wrist temperature values for both groups. RESULTS: Mean wrist temperature and M10 were not different when comparing the groups. The wrist temperature amplitude was reduced in the T1D group (p=0.039), due to a higher L5 (p=0.038). DISCUSSION: While the higher L5 observed in T1D could be explained by less efficient heat dissipation, the amplitude flattening coincides with that observed in elderly.

Latitudinal cline of chronotype.

The rotation of the Earth around its own axis and around the sun determines the characteristics of the light/dark cycle, the most stable and ancient 24 h temporal cue for all organisms. Due to the tilt in the earth's axis in relation to the plane of the earth's orbit around the sun, sunlight reaches the Earth differentially depending on the latitude. The timing of circadian rhythms varies among individuals of a given population and biological and environmental factors underlie this variability. In the present study, we tested the hypothesis that latitude is associated to the regulation of circadian rhythm in humans. We have studied chronotype profiles across latitudinal cline from around 0° to 32° South in Brazil in a sample of 12,884 volunteers living in the same time zone. The analysis of the results revealed that humans are sensitive to the different sunlight signals tied to differences in latitude, resulting in a morning to evening latitudinal cline of chronotypes towards higher latitudes.

Melatonin and circadian rhythms in autism: Case report.

Among the most co-occurring conditions in autism spectrum disorders (ASD), there are sleep disorders which may exacerbate associated behavioral disorders and lead to intensification of existing autistic symptoms. Several studies investigating the use of melatonin in the treatment of sleep disorders in ASD have shown comparative efficiency in sleep with little or no side effects. Here we report a case of ASD with non-24-hour rhythm and the effect of melatonin in circadian parameters by actigraphy. Visual analysis of the first 10 days recorded and the periodogram suggest that this patient showed a non-24-hour rhythm. This ASD subject showed before melatonin administration an activity/rest rhythm lower than 24 hours. The results show that melatonin increased approximately 4.7 times the regularity of circadian activity rhythm and resting staying on average between 00:00 and 06:00 and showed positive effects in improving the quality of sleep and behavior. So, the actigraphy showed an ASD subject with a non-24-hour activity/rest rhythm which changed this rhythm to a 24-hour rhythm after melatonin administration. This result reinforces the prospect of therapy with melatonin for synchronization (increased regularity) of endogenous rhythms and improve sleep quality and hence behavior and indicates the actigraphy as a choice tool to characterize several parameters of the activity/rest rhythm of ASD individuals.

Activity/rest rhythm of depressed adolescents undergoing therapy: case studies / Ritmo de atividade e repouso em adolescentes deprimidos durante terapia: estudos de caso

Abstract Introduction: Disorders of circadian rhythms have been reported in studies of both depressed children and of depressed adolescents. The aim of this study was to evaluate whether there is a relationship between the 24-hour spectral power (24h SP) of the activity/rest rhythm and the clinical course of depression in adolescents. Methods: Six 14 to 17-year-old adolescents were recruited for the study. They were all suffering from major depressive disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, as identified by the Schedule for Affective Disorders and Schizophrenia for School Aged Children: Present and Lifetime Version (K-SADS-PL). Depressive symptoms were assessed using the Children's Depression Rating Scale - Revised (CDRS-R) and clinical evaluations. Locomotor activity was monitored over a period of 13 consecutive weeks. Activity was measured for 10-minute periods using wrist-worn activity monitors. All patients were prescribed sertraline from after the first week up until the end of the study. Results: We found a relationship between high CDRS values and low 24-hour spectral power. Conclusions: The 24h SP of the activity/rest rhythm correlated significantly (negatively) with the clinical ratings of depression.

Resumo Introdução: Distúrbios do ritmo circadiano têm sido relatados em estudos com crianças e adolescentes deprimidos. O objetivo deste estudo foi avaliar se existe relação entre a potência espectral de 24 horas do ritmo de atividade e repouso e sintomas clínicos de depressão em adolescentes. Métodos: Seis adolescentes com idade entre 14 e 17 anos foram recrutados para o estudo. Eles foram diagnosticados com depressão maior de acordo com os critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV), identificados utilizando-se o instrumento Schedule for Affective Disorders and Schizophrenia for School Aged Children: Present and Lifetime Version (K-SADS-PL). Os sintomas depressivos foram avaliados pelo questionário Children's Depression Rating Scale - Revised (CDRS-R) e por avaliações clínicas. A atividade motora foi monitorada por um período de 13 semanas consecutivas e registrada a cada 10 minutos utilizando-se monitores de atividades usados no pulso. Todos os pacientes utilizaram o antidepressivo sertralina começando após a primeira semana até o final do estudo. Resultados: Foi observada uma relação entre escores altos no CDRS-R e valores baixos de potência espectral de 24 horas no ritmo de atividade e repouso. Conclusão: A potência espectral de 24 horas do ritmo de atividade e repouso apresentou uma correlação significativa (negativa) com os sintomas clínicos de depressão.

Development of sleep/wake, activity and temperature rhythms in newborns maintained in a neonatal intensive care unit and the impact of feeding schedules.

UNLABELLED: Biological rhythms in infants are described as evolving from an ultradian to a circadian pattern along the first months of life. Recently, the use of actigraphy and thermistors with memory has contributed to the understanding of temporal relations of different variables along development. The aim of this study was to describe and compare the development of the rhythmic pattern of wrist temperature, activity/rest cycle, sleep/wake and feeding behavior in term and preterm newborns maintained in a neonatal intensive care unit (NICU). METHODS: Nineteen healthy preterm and seven fullterm newborns had the following variables monitored continuously while they were in the NICU: activity recorded by actigraphy, wrist temperature recorded with a thermistor and observed sleep and feeding behavior recorded by the NICU staff with diaries. Subjects were divided in 3 groups according to their gestational age at birth and rhythmic parameters were compared. RESULTS: A dominant daily rhythm was observed for wrist temperature since the first two weeks of life and no age relation was demonstrated. Otherwise, a daily pattern in activity/rest cycle was observed for most preterm newborns since 35 weeks of postconceptional age and was more robust in term babies. Feeding and sleep/wake data showed an almost exclusive 3h rhythm, probably related to a masking effect of feeding schedules. CONCLUSIONS: We found that wrist temperature develops a daily pattern as soon as previously reported for rectal temperature, and with acrophase profile similar to adults. Moreover, we were able to find a daily rhythm in activity/rest cycle earlier than previously reported in literature. We also suggest that sleep/wake rhythm and feeding behavior follow independent developmental courses, being more suitable to masking effects.

Immunomodulation by classical conditioning in NZB/W (F1) mice: Lifespan and diurnal variation.

Systemic Lupus Eritematosus (SLE) is a systemic inflammatory disease often treated with the agent cyclophosphamide (CY), known by provoking important adverse reactions to the organism. Ader and Cohen have demonstrated an alternative way of administrating this agent based on pavlovian conditioning, in order to reduce the aggression caused by CY. Considering the influence of the temporal organization on learning and memory processes, the purpose of this study was to understand the temporal aspects involved in the conditioned immunomodulation. In a search for circadian modulation, we selected NZB/W (F1) female mice, a strain that spontaneously develop SLE. Divided into two major groups, the animals were submitted, in different phases of day, to a classical conditioning immunomodulation protocol, consisting in weekly parings of saccharin solution and CY injections. The success of the paradigm was evaluated by comparing lifespan among the groups. Simultaneously, it was monitored the water intake behavior, in order to correlate the stability of two rhythmic parameters, amplitude and spectral power density of the 24-h rhythm, with the progression of SLE. Our results indicate that mice could benefit from the conditioning task performed either in the light phase or in the dark phase of the LD cycle, as expressed by an increased lifespan. Concerning the rhythmic parameters, there was evidence of association between the rhythmic stability and the evolution of SLE, demonstrated by the maintenance of healthy levels of amplitude and spectral potency of the 24-h rhythm in animals exposed to the conditioning paradigm.

Environmental factors influencing biological rhythms in newborns: From neonatal intensive care units to home.

Photic and non-photic environmental factors are suggested to modulate the development of circadian rhythms in infants. Our aim is to evaluate the development of biological rhythms (circadian or ultradian) in newborns in transition from Neonatal Intensive Care Units (NICU) to home and along the first 6 months of life, to identify masking and entraining environment factors along development. Ten newborns were evaluated in their last week inside the NICU and in the first week after being delivered home; 6 babies were also followed until 6 months of corrected age. Activity, recorded with actimeters, wrist temperature and observed sleep and feeding behavior were recorded continuously along their last week inside the NICU and in the first week at home and also until 6 months of corrected age for the subjects who remained in the study. Sleep/wake and activity/rest cycle showed ultradian patterns and the sleep/wake was strongly influenced by the 3 h feeding schedule inside the NICU, while wrist temperature showed a circadian pattern that seemed no to be affected by environmental cycles. A circadian rhythm emerges for sleep/wake behavior in the first week at home, whereas the 3 h period vanishes. Both activity/rest and wrist temperature presented a sudden increase in the contribution of the circadian component immediately after babies were delivered home, also suggesting a masking effect of the NICU environment. We found a positive correlation of postconceptional age and the increase in the daily component of activity and temperature along the following 6 months, while feeding behavior became arrhythmic.

Activity/rest rhythm of depressed adolescents undergoing therapy: case studies.

INTRODUCTION:: Disorders of circadian rhythms have been reported in studies of both depressed children and of depressed adolescents. The aim of this study was to evaluate whether there is a relationship between the 24-hour spectral power (24h SP) of the activity/rest rhythm and the clinical course of depression in adolescents. METHODS:: Six 14 to 17-year-old adolescents were recruited for the study. They were all suffering from major depressive disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, as identified by the Schedule for Affective Disorders and Schizophrenia for School Aged Children: Present and Lifetime Version (K-SADS-PL). Depressive symptoms were assessed using the Children's Depression Rating Scale - Revised (CDRS-R) and clinical evaluations. Locomotor activity was monitored over a period of 13 consecutive weeks. Activity was measured for 10-minute periods using wrist-worn activity monitors. All patients were prescribed sertraline from after the first week up until the end of the study. RESULTS:: We found a relationship between high CDRS values and low 24-hour spectral power. CONCLUSIONS:: The 24h SP of the activity/rest rhythm correlated significantly (negatively) with the clinical ratings of depression.

Sleep and glycemic control in type 1 diabetes.

OBJECTIVE: Our aim in the present study was to elucidate how type 1 diabetes mellitus (T1DM) and sleep parameters interact, which was rarely evaluated up to the moment. MATERIALS AND METHODS: Eighteen T1DM subjects without chronic complications, and 9 control subjects, matched for age and BMI, were studied. The following instruments used to evaluate sleep: the Epworth Sleepiness Scale, sleep diaries, actimeters, and polysomnography in a Sleep Lab. Glycemic control in T1DM individuals was evaluated through: A1C, home fingertip glucometer for 10 days (concomitant with the sleep diary and actimeter), and CGM or concomitant with continuous glucose monitoring (during the polysomnography night). RESULTS: Comparing with the control group, individuals with diabetes presented more pronounced sleep extension from weekdays to weekends than control subjects (p = 0.0303). Among T1DM, glycemic variability (SD) was positively correlated with sleep latency (r = 0.6525, p = 0.0033); full awakening index and arousal index were positively correlated with A1C (r = 0.6544, p = 0.0081; and r = 0.5680, p = 0.0272, respectively); and mean glycemia values were negatively correlated with sleep quality in T1DM individuals with better glycemic control (mean glycemia < 154 mg/dL). CONCLUSION: Our results support the hypothesis of an interaction between sleep parameters and T1DM, where the glycemic control plays an important role. More studies are needed to unveil the mechanisms behind this interaction, which may allow, in the future, clinicians and educators to consider sleep in the effort of regulating glycemic control.

Sleep and glycemic control in type 1 diabetes

Objective Our aim in the present study was to elucidate how type 1 diabetes mellitus (T1DM) and sleep parameters interact, which was rarely evaluated up to the moment. Materials and methods Eighteen T1DM subjects without chronic complications, and 9 control subjects, matched for age and BMI, were studied. The following instruments used to evaluate sleep: the Epworth Sleepiness Scale, sleep diaries, actimeters, and polysomnography in a Sleep Lab. Glycemic control in T1DM individuals was evaluated through: A1C, home fingertip glucometer for 10 days (concomitant with the sleep diary and actimeter), and CGM or concomitant with continuous glucose monitoring (during the polysomnography night). Results Comparing with the control group, individuals with diabetes presented more pronounced sleep extension from weekdays to weekends than control subjects (p = 0.0303). Among T1DM, glycemic variability (SD) was positively correlated with sleep latency (r = 0.6525, p = 0.0033); full awakening index and arousal index were positively correlated with A1C (r = 0.6544, p = 0.0081; and r = 0.5680, p = 0.0272, respectively); and mean glycemia values were negatively correlated with sleep quality in T1DM individuals with better glycemic control (mean glycemia < 154 mg/dL). Conclusion Our results support the hypothesis of an interaction between sleep parameters and T1DM, where the glycemic control plays an important role. More studies are needed to unveil the mechanisms behind this interaction, which may allow, in the future, clinicians and educators to consider sleep in the effort of regulating glycemic control. Arch Endocrinol Metab. 2015;59(1):71-8 .

Sleep patterns and sleepiness among young students: A longitudinal study before and after admission as trainees and apprentices.

In developing countries, youngsters start to work during the high school years. Several studies have shown the difficulties associated with double shift, i.e. to work and study concomitantly, and its negative health consequences. Work and study time, as social synchronizers, have significant effects on the sleep-wake cycle (SWC). The purpose of this study was to evaluate sleep patterns and sleepiness in young students before and after entering the workforce as apprentices or trainees. Participants were 40 adolescents (26 males), 15-18 years old (mean = 15.8 years old) engaged in a first-job program at a non-governmental organization (NGO) while attending evening high school in the outskirts of the city of São Paulo, Brazil. The participants wore actigraphs (Ambulatory Monitoring, Inc.) and registered subjective sleepiness on KSS (Karolinska Sleepiness Scale) along 7 consecutive days, before and after admission to the job. Descriptive analyses were performed, and the variables were tested by means of the t-test and repeated measures ANOVA taking factors day of the week and time of the day into consideration. The participants' sleep duration on weekdays exhibited significant difference before and after starting work (F = 4.55; p = 0.04); the mean sleep duration was 492 min (SD = 44 min) before admission to the job to decrease to 405 min (SD = 58 min) after starting work. The mid-sleep time exhibited significant difference on weekdays before and after starting work (04:57 h; SD = 45 min versus 03:30 h; SD = 54 min; F = 4.91; p = 0.03). Finally, also sleepiness on weekdays (F = 6.41; p = 0.04) and at the waking time (F = 10.75; p < 0.01) exhibited significant difference before and after admission to the job. This article emphasizes the fact that social synchronizers like working during the day and studying in the evening changed the participants' SWC and were associated with sleep restriction. Brazilian governmental incentives notwithstanding, simultaneous performance of several activities by young workers should be considered as an occupational health hazard. Employment policies targeting young workers should take the dual shift - study and work - and its effects on the sleep-wake cycle into account.

Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia.

Melatonin is a neurohormone that works as a nighttime signal for circadian integrity and health maintenance. It is crucial for energy metabolism regulation, and the diabetes effects on its synthesis are unresolved. Using diverse techniques that included pineal microdialysis and ultrahigh-performance liquid chromatography, the present data show a clear acute and sustained melatonin synthesis reduction in diabetic rats as a result of pineal metabolism impairment that is unrelated to cell death. Hyperglycemia is the main cause of several diabetic complications, and its consequences in terms of melatonin production were assessed. Here, we show that local high glucose (HG) concentration is acutely detrimental to pineal melatonin synthesis in rats both in vivo and in vitro. The clinically depressive action of high blood glucose concentration in melatonin levels was also observed in type 1 diabetes patients who presented a negative correlation between hyperglycemia and 6-sulfatoxymelatonin excretion. Additionally, high-mean-glycemia type 1 diabetes patients presented lower 6-sulfatoxymelatonin levels when compared to control subjects. Although further studies are needed to fully clarify the mechanisms, the present results provide evidence that high circulating glucose levels interfere with pineal melatonin production. Given the essential role played by melatonin as a powerful antioxidant and in the control of energy homeostasis, sleep and biological rhythms and knowing that optimal glycemic control is usually an issue for patients with diabetes, melatonin supplementation may be considered as an additional tool to the current treatment.