The Role of Sleep in Type 2 Diabetes

Author: Erika Gebel, PhD, Diabetes Forecast May 2011

Beep. Beep. Beep. Reaching in utter exhaustion to silence the shrill cry of the morning alarm is a TV and movie cliché. And with good reason: Americans are indeed tired. According to the Centers for Disease Control and Prevention, 35 percent of Americans report getting less than the recommended seven to nine hours of sleep each night. This rampant deprivation has consequences, and not just grogginess: People who don’t get enough sleep are prone to a slew of health problems, including type 2 diabetes. How sleep (or the lack of it) affects diabetes is still being investigated, but it’s possible that for some people, preventing or controlling diabetes is as simple as getting an extra hour or two of z’s each night.

From Lab to Bed
Americans used to sleep more. Between 1959 and 2002, the percentage of people sleeping fewer than seven hours a night on a regular basis more than doubled. Meanwhile, the number of people with type 2 diabetes has soared. Could there be a connection? At the very least there’s an association between lack of sleep and diabetes, but it’s still not clear whether the former helps cause the latter and, if so, how.

The first real clue that sleep deprivation could lead to type 2 diabetes came from a 1999 study published in The Lancet. Healthy young people without any hint of diabetes came to live in a lab for a week. Their sleep was restricted to just four hours for six nights in a row. By the end of the experiment, their bodies’’ability to use glucose had radically shifted. “After a week of short sleep, their glucose metabolism looked like that of old men,” says Kristen Knutson, PhD, an assistant professor of medicine at the University of Chicago who studies the role of sleep in disease. “For a long time, people thought sleep was for the brain and only for the brain. This study showed that it was for the body, too.”

Since this landmark study, similar experiments have been conducted to explore the relationship between sleep and diabetes in more detail. A 2008 study in the Proceedings of the National Academy of Sciences sought to uncover the influence of deep sleep on the risk for diabetes. During sleep, the body cycles between rapid eye movement (REM) sleep and four stages of non-REM sleep, the deepest of which is called slow-wave sleep.

While volunteers in the study got a normal amount of total and REM sleep, the researchers restricted their slow-wave time. The result? Metabolic changes that increase the risk of diabetes. According to Knutson, this study showed that it’s not just how much sleep that matters, but you need good-quality sleep.”

These short-term experiments show that sleep can affect metabolism, but they can’t prove that inadequate sleep causes diabetes. For starters, it isn’t clear whether or not the body would eventually adjust to the sleep deficiency and normalize its metabolism over time. However, evidence that sleep and diabetes are connected has been established by assessing the health and sleep habits of groups of people. A 2010 study in Diabetes Care found that people with sleep problems – difficulty falling or staying asleep, sleeping fewer than five to six hours a night or more than eight to nine hours – are more likely to develop type 2 diabetes than sound sleepers.

Sleep may also affect blood glucose levels in people with diabetes. A 2006 study in the Archives of Internal Medicine found that those who report poor sleep quality have higher A1Cs (average blood glucose over two to three months). This finding is of concern because of the prevalence of obstructive sleep apnea (OSA) in people with diabetes.

OSA affects 2 out of 3 people with type 2 diabetes. It causes people to stop breathing repeatedly while sleeping because of an obstruction in the airway. This reduces how much sleep a person gets and disrupts the sleep cycle. OSA has been associated with high blood pressure. While OSA may lead to diabetes simply because of sleep deprivation, the person with sleep apnea is also deprived of oxygen, which adds a complicating factor. “There’s more than just sleep loss going on [with OSA],” says Knutson. “[Researchers] are still trying to disentangle sleep loss from oxygen deficiency.” Another confounding factor for scientists trying to understand the sleep-diabetes connection is obesity, which increases risk for both type 2 diabetes and OSA.

Sunrise, Sunset
While these studies point to sleep as a factor in diabetes, they have little to say about how this connection might work biologically. In recent years, though, scientists have discovered that the brain has a master internal clock that seems to be intricately connected to glucose metabolism and many other bodily functions.

This clock consists of a network of proteins, which function essentially as the clock’s gears. The proteins’ numbers systematically rise and fall over the course of 24 hours. This circadian rhythm repeats itself each 24-hour period and in most of the cells in the body. Specific genes encode each component of the clock and are critical to the proper functioning of the cell. “The question we want to know is: Do the genes themselves have a primary effect on glucose?” says Joseph Bass, MD, PhD, an associate professor at Northwestern University. “From [studies in] mice, the answer is yes.” With humans, though, the question is still unanswered.
While research into the link between sleep and metabolism is still in its infancy, one goal is discovering how behavior that’s out of step with circadian rhythm may trigger high blood glucose or raise the risk for diabetes. Sleeping too little or at the wrong times could somehow make the clock malfunction or perhaps disrupt biological schedules that are synchronized to the clock, such as insulin secretion. Another possibility is that the unnatural sleep patterns could prevent the master clock in the brain from correctly setting the time in the body’s organs, each of which has its own internal clock.

“[Biological] clocks evolved to optimize energy handling with respect to the rotation of the Earth,” says Bass. For example, during the day the clock primes the body for feeding. It helps the pancreas make more insulin during daylight hours to help the body use and store glucose. In his work, Bass has observed “rhythmic variations in glucose-stimulated insulin secretion.” At night, the opposite scenario takes hold; the body expects to be asleep and so the clock makes it easier to tap into stored energy by boosting production of glucagon. This is a hormone that raises blood glucose levels by mobilizing glucose stored in the liver and helps keep the body fueled during periods of fasting, like during sleep.

Eating or sleeping at the wrong times could upset the harmony between the body’s clock and behavior. Light is believed to set the clock in the brain, which is the body’s standard time.”Even seeing artificial light when the body expects it to be dark – say, while staying up late watching TV – may cause trouble. A study this year in the Journal of Clinical Endocrinology & Metabolism found that exposure to artificial light before bedtime can disrupt the biological clock. Diet may also tweak body clocks. A 2007 study by Bass in Cell Metabolism found that feeding mice a high-fat diet can alter circadian rhythm. A 2006 study in the Proceedings of the National Academy of Sciences showed that feeding mice at odd hours could change their internal clock mechanics and cause them to expect meals on a different schedule.

It may be a long time before researchers uncover the molecular basis for the connection between sleep and type 2 diabetes, but that doesn’t mean that better sleep can’t contribute right away to progress in preventing and treating the disease. “The work needed now is intervention,” says Knutson. “If you take habitually poor sleepers and make them sleep better, can you prevent or improve diabetes? If people can adhere to sleep, it could be a novel way to treat.”” Though the data aren’t conclusive, studies do suggest that helping people with obstructive sleep apnea rest easier can improve their blood glucose levels. There’s no need to wait for the scientific dust to clear. You can get a good night’s sleep tonight.