Sleep II: Glucose Intolerance and Hormone Dysfunction

My introduction to insulin will be important to understand before getting into today’s conversation. We will be discussing sleep, its affect on blood sugar levels, and its affect on serum insulin levels. If you don’t want to spend the five minutes reading the post on insulin, the most important takeaway is that insulin in a ginormous growth signal to the body. When insulin is present in the bloodstream, our ability to break down and burn stored body fat is blocked, while our ability to form and store new fat molecules is amplified. With that brief introduction, let’s dive in.

I don’t think anyone would argue that humans are incredibly diverse and adaptable. We live and learn to thrive in every environment the world has to offer (mostly). Adaptability is no more than responding positively to your environment. It is making subtle changes in your functioning to better facilitate your existence in that environment in the future. A prerequisite to being adaptable is the ability to sense your environment. Before you can begin to optimize outputs, you have to understand the inputs to the system. Sleep is a primary, pivotal, essential, etc., etc., input to our body functioning. The duration and quality of our sleep each night sends a truckload of data to our body. And being the adaptable creatures we are, our system processes that data and makes compensatory psychologic and physiologic changes. One of the huge levers our body can manipulate in response to this input of data is hormonal and metabolic functioning. If you remember from Sleep I, short sleep induces higher levels of ghrelin (a hormone associated with hunger) and lower levels of leptin (a hormone associated with satiety). These changes in chemical concentration lead to an overall subjective feeling of increased hunger. Today’s topic fits right along side this increased sensation of hunger. When we do not get adequate sleep we become less glucose tolerant. Meaning our blood sugar stays elevated for a longer time after eating, as do our levels of insulin. Short sleep leads to more insulin spending more time in our bloodstream.

In this small study participants were put through two different sleep regiments. Initially they were restricted to four hours in bed per night for six nights, and then allowed 12 hours in the bed for the next seven nights. In each condition they they were subject to a glucose tolerance test while also having their insulin levels measured. During the sleep restricted condition, there was a clear impairment of carbohydrate tolerance. Injected glucose was cleared from the body 40% slower after sleep restriction. They also measured the acute insulin response to be 30% lower in the sleep-debt condition. Glucose effectiveness, a measure of ability to dispose of glucose independent of insulin, was also 30% lower in the sleep debt condition. The combination of these outcomes would certainly lead to prolonged blood sugar elevation, and these differences in glucose tolerance are very similar to those seen in a non-insulin-dependent diabetic male compared to a normoglycemic male. Lastly, the researchers also measured glucose levels and insulin response to a 60% carbohydrate meal; opposed to the IV glucose injection which the above results were in reference to. They measured the increase in peak glucose after eating breakfast was higher in the sleep restricted state. However, peak glucose measurements following lunch and dinner did not differ much between the sleep states [1]. This is certainly no evidence of causation, I simply want to point out that there seems to be some level of hormonal and metabolic dysfunction in response to sleep restriction.

In this study researchers were investigating if sleep restriction impairs insulin signaling. In order for insulin to exert its effect at a cellular level, it first binds to a receptor on the outer membrane of a cell. This binding initiates a cascade of events (molecules tagging other molecules, turning them on) eventually resulting in the body’s ability to move glucose from the bloodstream into the cell. The researchers were able to measure a specific molecule in the insulin pathway (phosphorylated Protein Kinase B, aka pAkt) in order to assess insulin sensitivity of individuals in a sleep deprived state and in a well-slept state. They measured the concentration of insulin that was required to stimulate pAkt to adequate levels. In an insulin insensitive state, the amount of insulin required to reach this level of pAkt stimulation would be higher. In this experiment the participants were subjected to four and a half hours in bed to achieve the sleep deprived state versus eight and a half hours in bed to create the well-slept state (four consecutive days in each state). In the sleep deprived condition the amount of insulin required to elicit the desired pAkt response was 3-fold higher [2]. Another significant manifestation of hormonal disruption after short sleep.

There are many more studies out there, but I like to keep these posts relatively short. It is fairly obvious that there is some level of hormonal dysfunction that occurs after less than a week’s worth of inadequate sleep. Admittedly these studies are small, but we have seen some level of evidence for disruptions to ghrelin, leptin, insulin, and glucose tolerance. So for a quick summary of what we have covered so far: short sleep causes you to feel more hungry and less satisfied after a meal. You then have a decreased ability to deliver glucose from your bloodstream into your cells, elevating your blood sugar for a longer period of time. You also have a decreased response to insulin, further inhibiting your ability to remove glucose from the bloodstream and increasing the overall amount of insulin in your body throughout the day. There is certainly some level of a runaway feedback loop here, as prolonged blood sugar elevation further increases the demand for more insulin secretion. And remember, when you have high levels of insulin circulating, you cannot break down fat, but you can certainly build it.

My concern is not with the 40% slower glucose clearance the day after cramming for an exam or finishing a big project. I am concerned with what happens after 25 years of consistently getting 4-6 hours of sleep. What happens when endocrine dysfunction becomes our normal? What happens when our body is forced to adapt to metabolic conditions it would have only seen in the most stressful times in pre-historic life? Of course we will never know a definitive answer to these questions, but when you are dealing with something as ubiquitous as chronic disease, I naturally look at things equally ubiquitous, i.e. sleep, as possible culprits. The idealized, “I can sleep when I die,” needs to go, or those who believe it will surely meet that end sooner than they should have.

Best explorations

-Ryan; 6/5/2020

See Sleep I: An Evolutionary Imperative

References:

[1] Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435‐1439. doi:10.1016/S0140-6736(99)01376-8

[2] Broussard JL, Ehrmann DA, Van Cauter E, Tasali E, Brady MJ. Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study. Ann Intern Med. 2012;157(8):549‐557. doi:10.7326/0003-4819-157-8-201210160-00005

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