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1.
The Circadian Syndrome: is the Metabolic Syndrome and much more!
Zimmet, P, Alberti, KGMM, Stern, N, Bilu, C, El-Osta, A, Einat, H, Kronfeld-Schor, N
Journal of internal medicine. 2019;(2):181-191
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Abstract
The Metabolic Syndrome is a cluster of cardio-metabolic risk factors and comorbidities conveying high risk of both cardiovascular disease and type 2 diabetes. It is responsible for huge socio-economic costs with its resulting morbidity and mortality in most countries. The underlying aetiology of this clustering has been the subject of much debate. More recently, significant interest has focussed on the involvement of the circadian system, a major regulator of almost every aspect of human health and metabolism. The Circadian Syndrome has now been implicated in several chronic diseases including type 2 diabetes and cardiovascular disease. There is now increasing evidence connecting disturbances in circadian rhythm with not only the key components of the Metabolic Syndrome but also its main comorbidities including sleep disturbances, depression, steatohepatitis and cognitive dysfunction. Based on this, we now propose that circadian disruption may be an important underlying aetiological factor for the Metabolic Syndrome and we suggest that it be renamed the 'Circadian Syndrome'. With the increased recognition of the 'Circadian Syndrome', circadian medicine, through the timing of exercise, light exposure, food consumption, dispensing of medications and sleep, is likely to play a much greater role in the maintenance of both individual and population health in the future.
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The inflammatory response to simulated day and night emergency alarm mobilisations.
Tait, JL, Aisbett, B, Hall, SJ, Main, LC
PloS one. 2019;(6):e0218732
Abstract
PURPOSE Responding to emergency alarms is a daily occurrence for personnel in safety-critical occupations, and is associated with negative health outcomes in this population. The purpose of the present study was to determine the acute inflammatory response to an isolated emergency alarm mobilisation in both day and night conditions. METHODS Sixteen healthy males (mean age 25 ± 4 years) spent four days and nights in a sleep laboratory and were required to mobilise to an emergency alarm either during the day (1558 h), or from nocturnal sleep (0358 h). Pro (TNF-α, IL-1β, IL-8, IL-6) and anti-inflammatory (IL-4 and IL-10) cytokine responses to each alarm mobilisation were compared to time-matched control conditions without the alarm and mobilisation stimulus. RESULTS Analysis revealed no significant drift of cytokine levels at 1400 h across the study (P≥0.139). The plasma concentration of anti-inflammatory cytokine IL-4 was 84% greater in the 2-h sampling period following night alarm mobilisation compared to a night control of gentle awakening (P = 0.049), no other condition-by-time interactions were observed. The majority of inflammatory concentrations did not significantly change between alarm mobilisation and control conditions, in either day or night trials. CONCLUSIONS These findings may reflect the lack of a true emergency (and the perceived stress) for the alarm mobilisation, together with the neutralising effect of different circadian biorhythms on inflammatory cytokine concentrations.
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Focusing on the nuclear and subnuclear dynamics of light and circadian signalling.
Ronald, J, Davis, SJ
Plant, cell & environment. 2019;(10):2871-2884
Abstract
Circadian clocks provide organisms the ability to synchronize their internal physiological responses with the external environment. This process, termed entrainment, occurs through the perception of internal and external stimuli. As with other organisms, in plants, the perception of light is a critical for the entrainment and sustainment of circadian rhythms. Red, blue, far-red, and UV-B light are perceived by the oscillator through the activity of photoreceptors. Four classes of photoreceptors signal to the oscillator: phytochromes, cryptochromes, UVR8, and LOV-KELCH domain proteins. In most cases, these photoreceptors localize to the nucleus in response to light and can associate to subnuclear structures to initiate downstream signalling. In this review, we will highlight the recent advances made in understanding the mechanisms facilitating the nuclear and subnuclear localization of photoreceptors and the role these subnuclear bodies have in photoreceptor signalling, including to the oscillator. We will also highlight recent progress that has been made in understanding the regulation of the nuclear and subnuclear localization of components of the plant circadian clock.
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Diurnal influences of fasted and non-fasted brisk walking on gastric emptying rate, metabolic responses, and appetite in healthy males.
McIver, VJ, Mattin, LR, Evans, GH, Yau, AMW
Appetite. 2019;:104411
Abstract
Growing evidence suggests circadian rhythms, nutrition and metabolism are intimately linked. Intermittent fasting (IMF) has become an increasingly popular intervention for metabolic health and combining IMF with exercise may lead to benefits for weight management. However, little is known about the diurnal variation of fasted exercise. This study aimed to investigate the diurnal influences on gastric emptying rate (GER), metabolic responses, and appetite to fasted and non-fasted exercise. Twelve healthy males completed four 45 min walks in a randomised order. Walks were completed in the morning (AM) and evening (PM) and either fasted (FASTED) or after consumption of a standardised meal (FED). GER of a semi-solid lunch was subsequently measured for 2 h using the 13C breath test. Blood glucose concentration, substrate utilisation, and ratings of appetite were measured throughout. Energy intake was also assessed for the following 24 h. GER Tlag was slower in PM-FASTED compared to AM-FASTED, AM-FED, and PM-FED (75 ± 18 min vs. 63 ± 14 min, P = 0.001, vs. 65 ± 10 min, P = 0.028 and vs. 67 ± 16 min, P = 0.007). Blood glucose concentration was greater in the FED trials in comparison to the FASTED trials pre-lunch (P < 0.05). Fat oxidation was greater throughout exercise in both FASTED trials compared to FED, and remained higher in FASTED trials than fed trials post-exercise until 30 min post-lunch ingestion (all P < 0.05). No differences were found for appetite post-lunch (P > 0.05) or 24 h post-energy intake (P = 0.476). These findings suggest that evening fasted exercise results in delayed GER, without changes in appetite. No compensatory effects were observed for appetite, and 24 h post-energy intake for both fasted exercise trials, therefore, increased fat oxidation holds positive implications for weight management.
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5.
Clocking In, Working Out: Circadian Regulation of Exercise Physiology.
Duglan, D, Lamia, KA
Trends in endocrinology and metabolism: TEM. 2019;(6):347-356
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Abstract
Research over the past century indicates that the daily timing of physical activity impacts on both immediate performance and long-term training efficacy. Recently, several molecular connections between circadian clocks and exercise physiology have been identified. Circadian clocks are protein-based oscillators that enable anticipation of daily environmental cycles. Cell-autonomous clocks are present in almost all cells of the body, and their timing is set by a variety of internal and external signals, including hormones and dietary intake. Improved understanding of the relationship between molecular clocks and exercise will benefit professional athletes and public health guidelines for the general population. We discuss here the role of circadian clocks in exercise, and explore time-of-day effects and the proposed molecular and physiological mechanisms.
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The diurnal variation of bone formation is attenuated in adult patients with type 2 diabetes.
Hygum, K, Starup-Linde, J, Harsløf, T, Jørgensen, NR, Hartmann, B, Holst, JJ, Langdahl, BL
European journal of endocrinology. 2019;(3):221-231
Abstract
OBJECTIVE Bone turnover has a diurnal variation influenced by food intake, incretin hormones, the sympathetic nervous system and osteocyte function. The aim of the study was to compare diurnal variation in bone turnover in patients with diabetes and controls. DESIGN A clinical 24-h study with patients with type 1 diabetes (n = 5), patients with type 2 diabetes (n = 5) and controls (n = 5). METHODS Inclusion criterion: age >50 years. Exclusion criteria: diseases/medication that affect bone metabolism or recent use of incretin-based drugs. We drew blood samples hourly during the day and every 3 h during the night. We served an identical diet on all study days. We used repeated-measures one-way ANOVA to compare the levels of the investigated markers, and we quantified the effect of time by comparing group mean standard deviations. RESULTS The bone formation marker procollagen type 1 N-terminal propeptide showed a significant interaction between time and group (P = 0.01), and the mean standard deviation was lower in patients with type 2 diabetes compared with controls (P = 0.04) and patients with type 1 diabetes (P = 0.02). Other markers of bone formation and resorption showed significant effect of time. Levels of glucagon-like peptide-2, glucose-dependent insulinotropic peptide and sclerostin only showed significant effect of time (all P values 0.01), but levels of sclerostin tended to being highest in type 2 diabetes and lowest in controls. CONCLUSIONS The diurnal variation in bone formation is attenuated in patients with type 2 diabetes. This is not explained by changes in incretin hormone levels, but possibly mediated by sclerostin.
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Ghrelin is impacted by the endogenous circadian system and by circadian misalignment in humans.
Qian, J, Morris, CJ, Caputo, R, Garaulet, M, Scheer, FAJL
International journal of obesity (2005). 2019;(8):1644-1649
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Abstract
The human circadian system regulates hunger independently of behavioral factors, resulting in a trough in the biological morning and a peak in the biological evening. However, the role of the only known orexigenic hormone, ghrelin, in this circadian rhythm is unknown. Furthermore, although shift work is an obesity risk factor, the separate effects of the endogenous circadian system, the behavioral cycle, and circadian misalignment on ghrelin has not been systematically studied. Here we show-by using two 8-day laboratory protocols-that circulating active (acylated) ghrelin levels are significantly impacted by endogenous circadian phase in healthy adults. Active ghrelin levels were higher in the biological evening than the biological morning (fasting +15.1%, P = 0.0001; postprandial +10.4%, P = 0.0002), consistent with the circadian variation in hunger (P = 0.028). Moreover, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial active ghrelin levels (+5.4%; P = 0.04). While not significantly influencing hunger (P > 0.08), circadian misalignment increased appetite for energy-dense foods (all P < 0.05). Our results provide possible mechanisms for the endogenous circadian rhythm in hunger, as well as for the increased risk of obesity among shift workers.
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Can caffeine supplementation reverse the effect of time of day on repeated-sprint exercise performance?
Lopes-Silva, JP, Santos, JFDS, Franchini, E
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2019;(2):187-193
Abstract
The aim of this study was to evaluate if caffeine can reduce the negative influence of diurnal variations on repeated-sprint performance, in addition to investigating if caffeine in the afternoon would potentiate performance compared with the morning. Thirteen physically active men took part in this randomized, double-blind, placebo-controlled and crossover study. All participants underwent a repeated-sprint ability test (10 × 6 s cycle sprints, with 30 s of rest) at 60 min after ingestion of either 5 mg·kg-1 or placebo under 4 different conditions: morning with caffeine ingestion, morning with placebo ingestion, afternoon with caffeine ingestion, and afternoon with placebo ingestion. Total work, peak power (PP) and anaerobic power reserve (APR) were assessed. Oxygen uptake, heart rate, lactate concentration, and rating of perceived exertion were also measured during the repeated-sprint test. Total work (+8%, d = 0.2, small), PP (+6%, d = 0.2), and APR (+9%, d = 0.2) were significantly higher in the afternoon when compared with morning. However, physiological responses were not different between caffeine and placebo conditions. Repeated-sprint (10 × 6 s cycle sprint) performance was influenced by time of day, with lower performance in the morning compared with the afternoon. However, caffeine supplementation did not prevent the reduction in performance in the morning or improve performance in the afternoon.
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Dose-response between frequency of interruption of sedentary time and fasting glucose, the dawn phenomenon and night-time glucose in Type 2 diabetes.
Paing, AC, McMillan, KA, Kirk, AF, Collier, A, Hewitt, A, Chastin, SFM
Diabetic medicine : a journal of the British Diabetic Association. 2019;(3):376-382
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Abstract
AIM: To explore the dose-response between frequency of interruption of sedentary time and basal glucose (fasting glucose, the dawn phenomenon and night-time glucose) in Type 2 diabetes. METHODS In a randomized three-treatment, two-period balanced incomplete block trial, 12 people with Type 2 diabetes (age, 60.0 ± 3.2 years; BMI, 30.2 ± 1.4 kg/m2 ) completed two of three conditions: sitting for 7 h interrupted every 60 min (Condition 1), 30 min (Condition 2), and 15 min (Condition 3) by 3-min light-intensity walking breaks. The activPAL3 and FreeStyle Libre were used to assess physical activity/sedentary behaviour and continuous glucose profile. Standardized meals were provided, and changes in basal glucose of the nights and early mornings before and after treatment conditions were calculated (mean ± SE). RESULTS After treatment conditions, fasting glucose and duration of the dawn phenomenon were lower for Condition 3 (-1.0 ± 0.2 mmol/l, P < 0.02; -3.1 ± 1.3 h, P = 0.004) compared with Condition 1 (-0.1 ± 0.2 mmol/l; 1.9 ± 1.2 h). The magnitude of the dawn phenomenon was reduced in Condition 3 (-0.6 ± 0.4 mmol/l, P = 0.041) compared with Condition 2 (0.6 ± 0.3 mmol/l). Night-time glycaemic variability (coefficient of variation) was reduced in Condition 3 (-9.7 ± 3.9%) relative to Condition 2 (6.1 ± 4.8%, P < 0.03) and Condition 1 (2.5 ± 1.8%, P = 0.02). There was no change in night-time mean glucose. CONCLUSIONS Frequent interruptions of prolonged sitting with 3 min of light-intensity walking breaks every 15 min improves fasting glucose, the dawn phenomenon and night-time glycaemic variability, and this might be a simple therapeutic intervention to improve glucose control. Clinicaltrials.gov Identifier: NCT02738996.
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Circadian rhythms and exercise - re-setting the clock in metabolic disease.
Gabriel, BM, Zierath, JR
Nature reviews. Endocrinology. 2019;(4):197-206
Abstract
Perturbed diurnal rhythms are becoming increasingly evident as deleterious events in the pathology of metabolic diseases. Exercise is well characterized as a crucial intervention in the prevention and treatment of individuals with metabolic diseases. Little is known, however, regarding optimizing the timing of exercise bouts in order to maximize their health benefits. Furthermore, exercise is a potent modulator of skeletal muscle metabolism, and it is clear that skeletal muscle has a strong circadian profile. In humans, mitochondrial function peaks in the late afternoon, and the circadian clock might be inherently impaired in myotubes from patients with metabolic disease. Timing exercise bouts to coordinate with an individual's circadian rhythms might be an efficacious strategy to optimize the health benefits of exercise. The role of exercise as a Zeitgeber can also be used as a tool in combating metabolic disease. Shift work is known to induce acute insulin resistance, and appropriately timed exercise might improve health markers in shift workers who are at risk of metabolic disease. In this Review, we discuss the literature regarding diurnal skeletal muscle metabolism and the interaction with exercise bouts at different times of the day to combat metabolic disease.