Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans (original) (raw)
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Circadian clocks regulate cellular to organic and individual behavior levels of all organisms. Almost all cells in animals have self-sustained clocks entrained by environmental signals. Recent progress in genetic research has included identification of clock genes whose disruption causes metabolic abnormalities such as diabetes, obesity, and hyperlipidemia. Here we review recent advances in research on circadian disruption, shift work, altered eating behaviors, and disrupted sleep-wake cycles, with reference to management of type 2 diabetes.
Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity
Current biology : CB, 2015
Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents [1-7]. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)-a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Re...
Circadian control of glucose metabolism
Molecular Metabolism, 2014
The incidence of obesity and type 2 diabetes mellitus (T2DM) has risen to epidemic proportions. The pathophysiology of T2DM is complex and involves insulin resistance, pancreatic b-cell dysfunction and visceral adiposity. It has been known for decades that a disruption of biological rhythms (which happens the most profoundly with shift work) increases the risk of developing obesity and T2DM. Recent evidence from basal studies has further sparked interest in the involvement of daily rhythms (and their disruption) in the development of obesity and T2DM. Most living organisms have molecular clocks in almost every tissue, which govern rhythmicity in many domains of physiology, such as rest/activity rhythms, feeding/fasting rhythms, and hormonal secretion. Here we present the latest research describing the specific role played by the molecular clock mechanism in the control of glucose metabolism and speculate on how disruption of these tissue clocks may lead to the disturbances in glucose homeostasis.
Circadian regulation of glucose, lipid, and energy metabolism in humans
Metabolism: clinical and experimental, 2018
The circadian system orchestrates metabolism in daily 24-hour cycles. Such rhythms organize metabolism by temporally separating opposing metabolic processes and by anticipating recurring feeding-fasting cycles to increase metabolic efficiency. Although animal studies demonstrate that the circadian system plays a pervasive role in regulating metabolism, it is unclear how, and to what degree, circadian research in rodents translates into humans. Here, we review evidence that the circadian system regulates glucose, lipid, and energy metabolism in humans. Using a range of experimental protocols, studies in humans report circadian rhythms in glucose, insulin, glucose tolerance, lipid levels, energy expenditure, and appetite. Several of these rhythms peak in the biological morning or around noon, implicating earlier in the daytime is optimal for food intake. Importantly, disruptions in these rhythms impair metabolism and influence the pathogenesis of metabolic diseases. We therefore also ...
Sleep, 2015
A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact of sleep/circadian disruption in humans to move beyond measurements of insulin and glucose and conduct more in-depth phenotyping. There is also a need for the assessments of sleep and circadian rhythms as well as assessments for sleep-disordered breathing to be incorporated into all ongoing cohort studies related to diabetes risk. Studies in hum...
Increased Risk of Diabetes due to Obesity: Does Chronodisruption Play a Role?
Chronobiology and Obesity, 2012
The prevalence of obesity and type 2 diabetes mellitus (T2DM) has risen to epidemic proportions. The pathophysiology of T2DM is complex and involves insulin resistance, pancreatic b-cell dysfunction and visceral adiposity. Although it has been known for quite some time that a disruption of biological rhythms (as happens with shift work) increases the risk of developing obesity, insulin resistance and T2DM, more recent genomic evidence has further spiked the interest for the involvement of circadian rhythms (and their disruption) in the development of diabetes. In this chapter, we will start with an overview of the way in which glucose metabolism and the basal rhythm in plasma glucose concentrations and insulin sensitivity are regulated, after which we will discuss how a disruption of daily rhythms or a disruption of clock elements, may contribute to the development of insulin resistance. Glucose Metabolism: An Introduction Blood glucose is the most important energy source for the central nervous system. Since glycogen is neither stored nor produced in the central nervous system (CNS), plasma glucose concentrations must be maintained at a suf fi ciently high level for the organism to survive. It is therefore not surprising that the brain has several regulatory
The Circadian Syndrome: is the Metabolic Syndrome and much more!
Journal of Internal Medicine, 2019
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 socioeconomic 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 co-morbidities 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.
Diabetes Care, 2019
OBJECTIVE Sleep disturbances and circadian misalignment (social jet lag, late chronotype, or shift work) have been associated with worse glycemic control in type 2 diabetes (T2D). Whether these findings apply to adults with prediabetes is yet unexplored. We hypothesized that self-reported short sleep, poor sleep quality, and/or circadian misalignment are associated with higher glycemia, BMI, and blood pressure (BP) in adults with prediabetes or recently diagnosed, untreated T2D. RESEARCH DESIGN AND METHODS Our cohort included 962 overweight/obese adults ages 20–65 years with prediabetes or recently diagnosed, untreated T2D who completed a 2-h oral glucose tolerance test and validated sleep questionnaires. Independent associations of sleep and circadian variables with glycemia, BMI, and BP were evaluated with regression models. RESULTS The multiethnic cohort was 55% men, with mean ± SD age 52.2 ± 9.5 years and BMI 34.7 ± 5.5 kg/m2. Mean sleep duration was 6.6 ± 1.3 h. Poor sleep qual...
Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork
PLoS ONE, 2012
Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers.