SLEEP AND CIRCADIAN DISRUPTIONS: ADDLE METABOLIC PROCESSES

Mom always told you to get a good night’s rest. Here’s another reason why she might be right: A new study implicates a jet-lagged pancreas in the pathology linked to increased obesity and type 2 diabetes mellitus (T2DM). Published in Science Translational Medicine, the study says the two diseases gang up to hit the metabolism high and low, with sleep restriction increasing insulin resistance and circadian disruption decreasing insulin secretion.

The evidence from epidemiological research linking sleep disruption with metabolic perturbations is growing, but these studies do not answer the question of causality. For example, a study published in December in PLoS Medicine followed almost 180,000 female nurses. The investigators found that rotating night shift work was strongly associated with an increased T2DM risk.2 However, the affected women also gained more weight, ate a less healthful diet, and exercised less than their peers, muddying the contributions of night and rotating shift work schedules alone.

Problems of Causality

This muddled picture is always the case because night workers tend to be associated with less healthful lifestyle choices, especially diet options, said Orfeu M. Buxton, Ph.D., assistant professor in the division of sleep medicine at Harvard Medical School, associate neuroscientist at Brigham and Women’s Hospital in Boston, and lead author of the Science Translational Medicine paper. Dr. Buxton and his colleagues are trying to tease out the causality underlying the associations.

In a previous study of healthy men aged 20–35 years, his team showed that 7 nights of sleep restriction significantly reduced their insulin sensitivity, as assessed by an intravenous glucose tolerance test and euglycemichyperinsulinemic clamp.

A 28-Hour Day

The just-published study was much more ambitious. The team asked 21 healthy adults to spend 39 days under controlled laboratory conditions, in an individual suite with dim light and no time cues. After 6 days of a “sleep replete” condition, with sleep at a normal circadian time, the subjects spent up to 21 days with their sleep restricted to 5.6 hours during a circadian rhythm–disrupting 28-hour day schedule. They experienced feeding and sleep-wake cycles that were the equivalent of moving four time zones west every day. The subjects then had 9 days of recovery sleep opportunity of 10 hours per 24 hours at a normal circadian time. Their diet and activities were strictly prescribed. The researchers monitored a variety of metabolic parameters, such as resting metabolic rate, body temperature, blood glucose and insulin levels after a meal, and more.

Pancreatic Problem

Glucose elevations following a meal in the morning were much higher, and they were sustained for several hours afterward at a higher level than when the subjects were rested. “Much to our surprise, the pancreas secreted far less insulin when subjects were circadian disrupted than when subjects were well rested and in phase,” Dr. Buxton told Endocrine News. “So, sleep restriction alone and circadian disruption both increase diabetes risk, but the difference is that sleep restriction does so by reducing insulin sensitivity without any change of insulin response, whereas circadian disruption does so by greatly decreasing the insulin response.”

Another important finding was that the test subjects experienced a reduction in resting metabolic rate of about 8%. If such a reduction continued with no cut in caloric intake or increase in activity, it could lead to a weight gain of about 10 pounds in a year, which implies an obesity risk.

Of course, the researchers noted other metabolic perturbations. Glucose and cortisol concentrations rose above baseline levels; leptin levels were slightly lower, and ghrelin levels were slightly higher. The deviations returned to normal during the 9 days of recovery sleep. A surprise in the results was the lack of an age effect. The changes were no more pronounced in older subjects than in younger ones.

The Double Whammy

Some critics have complained that the researchers sacrificed clarity by combining circadian disruption with sleep restriction, but Dr. Buxton said the two are inseparable in the lives of night workers and rotating night workers. “Your circadian clock drives you to be alert during the biological day and asleep during the biological night. Most night workers have extreme difficulties getting the amount of sleep they would at night when they have to recover during the day,” he said. Outside noise, light, and the phone interrupt sleep, and it’s much harder to get back to sleep during the day.

“We know little about the biological mechansims through which sleep disturbance leads to metabolic changes,” said Frank Hu, M.D., Ph.D., M.P.H., professor of nutrition and epidemiology at the Harvard School of Public Health. He added that the two studies by Dr. Buxton “provide strong evidence that sleep deprivation or shift work can actually decrease insulin sensitivity and decrease insulin secretion.”

Sleep as a Lifestyle Choice

Dr. Hu is the lead author of the previously mentioned epidemiological study linking shift work and diabetes in nurses. He also co-authored a prospective study on 4-year weight gain that found the effect of a short sleep period alone on weight gain to be small, but also found that short sleep was associated with other problems, such as skewing diet choices away from healthful items like yogurt and walnuts and toward sugary drinks and unhealthful snacks.

Chronic sleep deprivation could be a factor contributing to the obesity epidemic. The average sleep duration in the United States has declined by more than an hour a night in the past 40 years, and has fallen below 7 hours per night. Studies show that the optimal amount of sleep for most individuals is in the range of 7–8 hours a night.

Dr. Hu said when clinicians talk to patients on combating metabolic syndrome by improving their diet and lifestyle, perhaps it’s time to broaden lifestyle counseling to include tips on better sleep hygiene as well, like Mom’s admonition to get to bed on time. “To a large degree, sound sleep is actually as important as good diet and regular exercise.”

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