sleep and obesity.JPGSleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed.

Sleep and circadian rhythms are known to modulate or control daily patterns in human physiology with importance for normal metabolic function. Daily patterns of energy expenditure (4), hormones, and lipids involved in energy metabolism (e.g., leptin, ghrelin, PYY, glucose, insulin, glucocorticoids, catecholamines, fatty acids, triglycerides) are regulated by sleep and circadian rhythms (48). Disruption of sleep and circadian rhythms is increasingly evident as a contributing factor to impaired physiological function and disease processes, especially with respect to metabolic dysregulation (912). Sleep deficiency occurs as a result of a number of untreated sleep problems including insufficient sleep schedules, insomnia, sleep apnea, periodic limb movement disorder, narcolepsy, shift work and shift work disorder, night eating syndrome and sleep-related eating disorder (1315). Metabolic disorders associated with sleep deficiency include unwanted weight gain, obesity, and T2D (Fig. 1) (1619). We are now beginning to understand how sleep and circadian disruption contributes to metabolic dysregulation and how treatment of sleep and circadian problems may improve metabolic treatment outcomes.

Glucose metabolism is also disturbed during insufficient sleep. Findings from a seminal study on this topic showed that six nights of a 4h per night sleep opportunity reduced glucose clearance by 40% and the acute insulin response to glucose by 30% during an intravenous glucose tolerance test (IVGTT) (29). This outcome is similar to differences between young glucose tolerant and older glucose intolerant adults. Findings from a similar study (16) indicated that seven nights of 5h sleep opportunity in healthy men decreased insulin sensitivity assessed by the hyperinsulinemic euglycemic clamp. In a longer duration study (30), 14 days of a 5.5h per night sleep opportunity reduced oral glucose tolerance and IVGTT insulin sensitivity (Si) in healthy subjects. Insufficient sleep of four nights of a 4h per night sleep opportunity has also been shown to decrease cellular adipose insulin signaling (30%) and whole body Si (16%) (31). Collectively, these controlled laboratory studies support the hypothesis that insufficient sleep can contribute to impaired metabolism. If persistent, such metabolic changes could contribute to or worsen T2D. Additional research is needed to improve our understanding of potential mechanisms underlying impaired metabolism associated with insufficient sleep and to investigate the potential benefit of increasing sleep in short sleepers with metabolic disorders.

Findings from an epidemiological study indicated that diabetes is also associated with central sleep apnea (cessation of respiratory effort) and periodic Cheyne Stokes breathing (65). Central sleep apnea and periodic breathing may be associated with diabetic autonomic neuropathy in diabetic patients (66). Like obstructive sleep apnea, central sleep apnea and periodic breathing may contribute to metabolic dysregulation in diabetic patients.