Research Reviews

Research Review: Less sleep, more insulin resistance?

by Jennifer Koslo

Most of us would love more sleep. Sure, good nutrition and exercise can offset some of the effects of sleep deprivation. But chronically inadequate sleep can lead to insulin resistance and type 2 diabetes. Here’s how. And why.

Deep thoughts on deep sleep

Question: What is sleep?
Maharishi: How can you know sleep when you are awake? The answer is to go to sleep to find out what it is.

Question: But I cannot know it in this way.
Maharishi: This question must be raised in sleep.

Question: But I cannot raise the question then.
Maharishi: So that is sleep.

–Attributed to: Sri Ramana Maharishi

Why do humans sleep?

If you’re a fan of the Twilight series, you’ll know that the vampires didn’t need to sleep. But their bodies were also transformed into the embodiment of perfection — frozen in time with no need for bodily maintenance.

Not so with us mere mortals. We need to sleep or we become pretty dang cranky, have memory lapses, drive sloppily, and increase our risk of developing obesity, high blood pressure, heart disease, insulin resistance and type 2 diabetes (1).

And while you may not have ever put much thought into the functions of sleep, most folks will admit that there’s nothing better than a solid night’s sleep for improving mood and energy levels. Mood, memory, and learning are all more or less controlled by our central nervous system and studies have shown that sleep plays a key role (2).

One way to understand the functions of sleep is to compare it to eating.

It’s pretty easy to understand why we eat: We need to consume nutrients so that our bodies can grow, repair tissue and function properly.

Both sleeping and eating are regulated by powerful internal drives. Go too long without food and your stomach rumbles, your blood sugar drops, and you’re forced to satisfy your hunger. The same thing happens with sleep — you can survive for a while on limited sleep (just ask some sleep-deprived new parents or exam-cramming college students), but eventually you’ll just get too sleepy and have to give in to the urge to go ball up in a corner and grab a few ZZZs.

Our central nervous system can restore itself while we sleep, and we seem to need this to function properly.

Sleep duration & chronic disease

Sleep also has metabolic functions — processes essential for sustaining life. Metabolic processes are influenced by hormones, many of which are affected by sleep. For example, hormones involved in sleep include:

  • Leptin and ghrelin, two hormones involved in appetite control;
  • Insulin, a key player involved in processing the foods that we eat and maintaining normal blood sugar levels; and
  • Melatonin, secreted by the pineal gland, is involved in both regulating our body clock (aka circadian rhythm) as well as keeping glucose levels stable (3).

So while we still aren’t sure how it all works, ample evidence from laboratory studies and epidemiological studies shows that not getting enough sleep has long-term metabolic consequences, including the development of insulin resistance, type 2 diabetes, obesity, heart disease and high blood pressure (4).

Sleep duration and insulin resistance

Insulin resistance seems to be a key underlying factor in most of these chronic diseases. Insulin resistant cells don’t properly respond to the normal actions of the hormone insulin. This is bad news.

After you eat a meal, the starches get digested and broken down into glucose, a monosaccharide or simple sugar, which then enters the bloodstream as fuel for our cells. When the glucose level gets high enough, your pancreas releases insulin. The insulin heads for the cells in your muscle and fatty tissue and attaches to receptors on the cells. This signals to your cells to take in the glucose and use it for energy.

At least, that’s the goal.

But when people are resistant to insulin, their cells don’t “hear” insulin knocking at the door. Insulin may not bind to the cells, which means it doesn’t move the glucose into the cells. Glucose is “locked out”. High levels of glucose keep circulating in the blood, wandering around, causing all sorts of problems.

Many factors cause insulin resistance, including being overweight, inactivity, poor diet (especially one high in processed sugars/starches), aging, genetics, some medications and, that’s right, insufficient sleep (3-6).

The role of subcutaneous fat

You might not like it on your butt or belly, but subcutaneous fat (the fat under our skin) is actually very important in regulating our energy balance and overall health.

Healthy subcutaneous fat depends on insulin being able to do its job. If insulin metabolism isn’t working properly, we risk type 2 diabetes and other metabolic disorders.

Research question

Research has already shown that sleep deprivation can create insulin resistance and make it worse. Question is, how? In this week’s research review, the researchers look at whether not getting enough sleep makes subcutaneous fat less responsive to insulin.

Broussard, J.L., Ehrmann, D.A., Van Cauter, E., Tasali, E., Brady, M.J. Impaired insulin signaling in human adipocytes after experimental sleep restrictions. Ann Intern Med 157(8): 549-557, October 16, 2012.

Methods

This study used a randomized, two condition, two period crossover design.

Research subjects were given two separate conditions, in random order. Each condition lasted four consecutive days under controlled laboratory conditions:

  • Condition 1: 4.5 hours of sleep per night
  • Condition 2: 8.5 hours of sleep per night

At the end of each condition, the researchers took biopsy samples of abdominal subcutaneous fat tissue in order to examine whether different sleep durations affected the fat cells’ insulin sensitivity.

Subjects then waited 4 weeks before starting the other round of sleep testing — a “washout” period where researchers try to ensure that the effects of one experimental condition don’t affect the next testing condition.

Subjects

This study had a very small sample size, which is one of the limitations, but seriously, unless I was paid a pretty good sum of money I don’t think I would have volunteered for this one. Six men and one woman participated, for a total of 7 people.

Likely, these were graduate students: They had a mean age of 23.7 years and a mean BMI of 22.8 kg.m2 (normal is 18.5 – 24.9) with a mean body fat percentage of 22.3% (pretty lean individuals).

Participants were prescreened and didn’t have a history of chronic disease, shift work, depressed mood, or recent travel across time zones. They didn’t use prescription meds, smoke, or drink a lot of alcohol (wait… maybe these weren’t grad students), and had normal blood panel results and a healthy heart. The subjects also reported that they normally slept for about 7.5 to 8.5 hours a night.

Experimental protocol

Before each testing condition, the participants were instructed to stick to a standardized schedule of bedtimes and mealtimes. No naps allowed. To make sure that they complied with their sleep instructions, the participants wore an Actiwatch on their wrists, which recorded the amount of time they spent sleeping.

After one week of required “pre-monitoring”, the participants had to basically camp out at the lab for four days in a row to complete the testing protocol. They did this twice.

Sleep duration

For the 8.5 hours in bed condition, sleep time was 11:00 p.m. to 7:30 a.m., or normal sleep for four days in a row. For the 4.5 hours in bed condition, sleep time was 1:00 a.m. to 5:30 a.m. for four days in a row.

Sleep was recorded by polysomnography, which by definition means “sleep study” but it also involves an instrument that measures brain waves. Standard polysomnographs use electrodes placed on the scalp. In this study the recordings were visually scored in 30 second-epochs (i.e. periods of time) as rapid eye movement (REM), non-REM sleep, and wake activity.

Waking hours

It wasn’t entirely clear what the participants did to occupy themselves during their waking hours. Whatever it was, it was “under sedentary laboratory conditions” so hopefully they had some good books to read or old episodes of Oprah.

Diet

Researchers tightly controlled participants’ eating. Subjects got 3 meals per day, each with a similar amount of calories, and they had to eat it all within 20 minutes. (Guess they don’t follow one of our most important PN habits — eating slowly.)

No caffeinated beverages, no outside food. No popping popcorn to go with the book reading or movie watching, or whatever else they did during their waking hours. A registered dietitian supervised meal prep to ensure that the meals met the protocol guidelines.

Frequently sampled intravenous glucose tolerance tests (FSIVGTTs)

I dare you to say that 3 times fast! On the 4th day of each condition, the participants were subjected to a glucose tolerance test. The description of this test sounds worse than it is, but if you have a squeamish stomach you may want to look away.

After an overnight fast, the participants had an IV inserted and first, 3 blood samples were taken every 5 minutes for 15 minutes to get baseline readings. Then glucose was given as an IV bolus and blood samples were taken at 27 intervals over the course of 240 minutes. Yikes! Then to top it off they were administered insulin through IV at the 20 minute mark.

Biopsy of subcutaneous abdominal fat

After each of the sleep conditions, the participants had some fat cells removed from just under the skin next to the belly button.

Biopsies were taken from opposite sides because ouch! I think they would have lost a few participants if they took it from the same site. Plus they didn’t want the inflammatory response interfering with the test results.

Measures

Insulin signaling assay

In order to find out what effect sleep duration had on the insulin signaling pathway in the body, the researchers needed to measure a protein called Akt.

Under normal conditions, Akt responds to the presence of insulin by becoming activated (aka phosphorylated at amino acid – serine 473 to be exact). Once activated, Akt signals the uptake of glucose into the cells, like one of those folks with the fluorescent cones who direct airplanes at the airport.

This is where the collected subcutaneous abdominal fat cells come into play. The fat cells were treated to remove connective tissue and then were exposed to increasing amounts of insulin. Then researchers measured the ability of insulin to activate Akt.
Insulin Signalling Research Review: Less sleep, more insulin resistance?

FSIVGTT

The glucose tolerance test was used to estimate total body insulin sensitivity. The researchers chose this test because it’s been used in other studies to document how sleep adversely affects glucose metabolism and insulin sensitivity. It’s always good to use measures that have been used before, so there’s a basis for comparison.

Results

Does sleep restriction reduce insulin sensitivity in subcutaneous fat cells, which play a key role in energy metabolism and balance? Yes.

Just 4 days in a row of inadequate sleep made the fat cells in the abdominal area insulin-resistant and reduced total body insulin sensitivity.

Polysomnography

The 4.5 hour sleep condition decreased REM sleep by about 56% compared to the 8.5 hour condition, and resulted in a cumulative sleep loss of 14 hours over the course of the four days.

Cellular insulin sensitivity in adipocytes (fat cells)

After normal sleep, insulin caused a dose-dependent increase in active Akt or pAkt (this is what you want so that glucose uptake into the cells occurs). This means that as insulin went up, Akt signalling went up — the cells recognized and effectively responded to the insulin. That’s good.

In contrast, sleep restriction significantly reduced active Akt. In other words, as Akt went down, so did the cells’ ability to use insulin properly. That’s bad.

Researchers also checked the ratio of active Akt to the total pool of Akt (pAkt /Akt) and again, with sleep restriction, the ratio was significantly lower. So, not only is Akt not doing its job, there’s not as much of the active Akt around to help out.

The last measure was the ratio of pAkt to insulin concentration. In the sleep restricted condition, the cellular insulin sensitivity was reduced by 30%.

FSIVGTT

Total body insulin sensitivity was reduced by 16% after 4 days of sleep restriction. Again: just four days!

Conclusion

After four days of sleep restriction, lean individuals’ fat cells were 30% less insulin sensitive. And total body insulin sensitivity (i.e. the ability of all tissues to use insulin properly) went down 16%.

This is an important finding, because for the first time, we can see a specific molecular mechanism involved in reduced insulin sensitivity after sleep deprivation. This reduced insulin sensitivity can easily create or worsen future obesity and type 2 diabetes if left unchecked.
This same pathway is also involved in leptin secretion and lipid metabolism. It’s a one-two punch.

A major limitation of this study was the small sample size and the severe and short duration of the sleep deprivation. Researchers also only assessed one protein involved in the insulin-signaling pathway.

However, just 4 days of sleep deprivation created significant metabolic disturbances in lean, healthy young participants. Future studies could look at other parameters including leptin, ghrelin, and cortisol and include more subjects for a longer period of time. Regardless, this is sobering data.

Bottom line

Need an excuse for sleeping in or taking that Sunday afternoon nap? Well here it is!

Take sleep deprivation seriously

Stop saying “You’ll sleep when you’re dead” or high-fiving yourself for your 4-pot-a-day dark roast habit. Get real about the health risks of poor sleep.

Strong evidence shows that lack of sleep is involved in the development of many chronic diseases. Sleep deprivation disrupts important metabolic pathways involved in energy balance and regulation.

Conversely, getting enough sleep makes you smarter, happier, leaner, and healthier.

If you must be sleep deprived, be strategic

If you’re a new parent or otherwise can’t control your sleep deprivation, do your best to have other good health habits.

You can improve insulin sensitivity with regular movement (even as little as 30 min of daily walking will do it) and thoughtful food choices (for example, by choosing slow-digesting high-fibre carbs, and rarely eating refined/processed foods).

Have a pre-sleep routine

Future treatments for disrupted metabolisms could be as simple as a “good sleep prescription”, which is why we include a pre-bed ritual as one of our key health habits in our coaching programs. If you’re struggling to get your ZZZs, try a basic pre-sleep routine:

  • Establish and stick to a regular bedtime.
  • Turn off your electronic screens (TV, computer, smartphones, etc.) and distractions at least 30-60 min before bed. (Facebook and Angry Birds can wait.)
  • Make sure your bedroom is comfortable, cool, and as dark as possible. And don’t use your bedroom for working.
  • Avoid large meals, caffeine and alcohol close to bedtime — although a small healthy pre-bed snack can help.
  • Practice relaxation techniques like deep breathing and progressive muscle relaxation.
  • Try herbal teas such as chamomile or lavender.

Bonne nuit!

References

Click here to view the information sources referenced in this article.

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