Laboratory and epidemiological studies continue to show that sleep curtailment and/or decreased sleep quality can disturb neuroendocrine control of appetite, leading to overeating, and can decrease insulin and/or increase insulin resistance, both steps on the road to Type 2 diabetes.
On April 22, at the Experimental Biology 2009 meeting in New Orleans, a panel of leading sleep researchers describes recent and new studies in this fast growing field. The session is part of the scientific program of the American Association of Anatomists (AAA).
Short sleep, poor sleep: novel risk factors for obesity and for type 2 diabetes.
Dr. Eve Van Cauter, University of Chicago, is a specialist in the effect of circadian rhythms on the endocrine system and has conducted several studies in which short-term sleep restriction damaged the body's ability to regulate eating by lowering levels of leptin, the hormone that tells the body when it has had enough. In the AAA symposium, Dr. Van Cauter describes other recently published studies from her group, one showing that only three days sleep disruption is sufficient to increase insulin resistance in humans (thus causing the body to need higher levels of insulin) and a large epidemiological study showing that short sleep over a five year period causes an increase in systolic blood pressure.
Dr. Van Cauter also describes work in other laboratories, such as a multi-center study, headed by Dr. Sanjay Patel, Case Western Reserve Medical School, in which thousands of older patients wore wrist monitors 24 hours a day, allowing researchers to objectively document how long and well they slept instead of relying on self reports. Some scientists and clinicians had believed that the relationship of short/poor sleep and obesity was important in children and adults but waned with age. Dr. Van Cauter says this study found that short/poor sleep was associated with obesity regardless of age.
Energy metabolism during chronic sleep deprivation: sleep less, eat more, don't gain weight, yet show signs of progression toward diabetes.
Panel member Dr. Michael Koban, Morgan State University, reports a new study in which sleep restriction in rats led to glucose intolerance, a prediabetic state in which the blood glucose remains higher than normal after glucose challenge. Significantly, this is the first rodent study of sleep deprivation in which there was no association between glucose dysregulation and weight gain.
For 13 days, the rats were kept awake 20 of every 24 hours, then returned to their cages where they could sleep. As in a number of other studies of sleep deprivation or poor sleep in humans and rats, the sleep restricted rats greatly increased their consumption of food, in this case a human food supplement laced with chocolate, which rats love and which allowed for a more precise measure of consumption than rat chow, which often gets strewn around like bird seed in a feeder. Control rats allowed to sleep as much as they wanted also had access to the same treat, but ate less.
Significantly, while the sleep-deprived rats ate substantially more than well-rested rats, they did not gain weight. This was due, says Dr. Koban, to an increase in energy metabolism. The resting metabolism of the sleep-deprived rats rose sharply, coupled with rapid mobilization of hepatic and muscle glycogen followed by reduction in abdominal white adipose tissue.
Further studies are now underway in the Koban laboratory that more closely mimics chronic sleep deprivation in humans. The researchers believe that extending sleep restriction will produce more pronounced glucose intolerance in which glucose levels do not return to normal levels for a longer period, thus providing more evidence that not sleeping enough could lead to diabetes in humans. The researchers also are looking for mechanisms to explain the change in metabolism related to sleep deprivation and the dissociation between weight gain and glucose dysregulation and insulin resistance.
Stress-related behaviors and hormone changes after prolonged sleep deprivation – and environmental factors that appear to modify them
Dr. Deborah Suchecki, Universidade Federal de Sao Paulo, describes how prolonged sleep deprivation activates the neuroendocrine stress response, as measured by increased blood levels of the stress-related hormones adrenaline, adrenocorticotropic hormone (ACTH), and corticosterone. Earlier studies have shown that sleep restriction in animals can gradually change brain and neuroendocrine systems in ways similar to those seen in stress-related disorders such as depression, while epidemiological studies suggest that sleep restriction may be an important risk factor for cardiovascular and other diseases linked to stress.
In the sleep panel at Experimental Biology 2009, Dr. Suchecki reports from two new studies in her laboratory that suggest how environmental factors can modulate the stress response to sleep deprivation. In the first, group support (rats were sleep deprived in groups of 10) reduced both anxiety-like behavior and the blood levels of stress hormones.
In the second, having access to water sweetened with saccharin or sucrose lowered the levels of stress hormones in sleep-deprived animals, although the levels still remained higher than animals with sufficient sleep. Despite the fact that sleep-deprived animals consumed a large amount of the sucrose solution, they still consumed more chow than their control counterparts and lost just as much weight as the water-only group, indicating an intense metabolic change. The reason, discovered Dr. Suchecki, was that insulin levels were greatly reduced after sleep deprivation and remained low after four days of sleep recovery, whereas corticosterone levels remained high even after the 96 hours of recovery. The loss of body weight appeared related to elevated corticosterone levels. Stimulation of feeding behavior results from, among other factors, increased activity of orexin (hypocretin) neurons in the hypothalamus, the brain center that controls motivated behaviors and the stress response.
CNS changes after chronic sleep deprivation have role in both food intake and metabolism.
Symposium chair Dr. Gloria Hoffman, also of Morgan State University, presents studies that explain the role of the central nervous system pathways in stimulating feeding and causing metabolic changes associated with progression to diabetes. Specifically, increased production of the neurotransmitter neuropeptide Y and decreased production of proopiomelanocortiini products in the hypothalamus explain the hyperphagic response.
Although the CNS's role in regulating metabolic rate is not well understood, she believes that histamine might be involved. Histamine neurons not only affect the maintenance of wakefulness but also are regulators of peripheral metabolism. In sleep deprived rats, elevations in the glucose to insulin ratio were positively correlated with an increase in histamine expression that raises the possibility that a dysregulation of histamine function during impaired sleep might serve to trigger metabolic and other changes leading to diabetes.
The scientists agree that as sleep curtailment becomes more common in industrialized countries it becomes increasingly important to understand how limited or poor quality sleep produces changes that can lead to obesity and diabetes, both epidemic in the developed world. More and more scientists are jumping on board with these lines of investigation, says Dr. Hoffman, and there is an increased demand for information on the part of health professionals and members of the general public, many of whom consider themselves sleep deprived.
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