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


[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

Growth of the Human: How Insulin Works



  • insulin is a hormone secreted to lower blood sugar levels
  • insulin is a body wide signal for growth
  • high levels of insulin promote the storage of energy in the form of glycogen and triglycerides (fat)
  • high levels of insulin BLOCK the breakdown of fat
  • insulin is affected by type of food, timing of food, exercise, sleep, and many other lifestyle factors

Insulin is one of the most important molecules in our body. Remember that hormones are molecules secreted by one part of the body in order to communicate a message to another part. They are able to relay information through the bloodstream, allowing systemic responses to certain environmental conditions. Blood sugar is one of the most tightly regulated parameters in our body, as we run into serious problems with both high and low blood sugar levels. Insulin is a hormone secreted by the pancreas when elevated blood sugar has been sensed. Although insulin is one of our body’s primary tools to keep our blood glucose (sugar) in check, it is not a master tool. Insulin only acts to lower blood sugar levels. Typically in response to eating, our blood sugar levels rise. This is when insulin is excreted from the pancreas into the bloodstream. Once insulin is flying around our blood vessels, it starts screaming its message to all the cells it comes into contact with, and its primary message is: Energy is available! GROW, STORE ENERGY, and GROW MORE!

Throughout all levels of biology, a primary task of the organism is to sense energy availability. In the evolutionary world, energy was always hard to come by, so the ability to detect available energy was a crucial advantage that essentially all organisms developed. It would be a catastrophic failure for an organism to try to grow and divide while resources were scarce, and it would be an equally fatal mistake for the organism to fail to grow and store energy when the resources were available. As it turns out, the molecular switches that control this decision of anabolism (building) versus catabolism (breaking down) are often central to our health and longevity. There are a handful of these high level decision makers in our body, but today’s post will focus solely on insulin.

First we must keep in mind the big picture: when insulin is in the blood, it is a body wide signal for anabolism or growth. From here we can zoom in on some of the details of insulin’s action. As we mentioned above, a primary task of insulin is to lower blood glucose levels. When insulin comes into contact with muscle cells and fat cells, it induces a specific effect, essentially unlocking the cell for glucose entry. When a muscle or fat cell grabs (binds) a molecule of insulin from the bloodstream, a cascade of events is set off inside the cell. The end result of this process is the the insertion of the GLUT4 transporter into the cellular membrane of a muscle or fat cell. A quick digression on cellular membranes; these are structures that form the boundary of cells and organelles (smaller structures inside of cells). The membrane is the outer layer controlling what comes in and what goes out. If the bloodstream is a superhighway connecting the different parts of our body, the membranes completely control who is allowed to exit the highway and enter the city (cells). Back to insulin. So insulin binds to the fat or muscle cell, resulting in GLUT4 transporters being shoved into the cellular membrane. The GLUT4 transporter essentially acts like a very specific claw, searching the bloodstream for molecules of glucose, grabbing the glucose from the bloodstream, and transporting it inside the cell. Without GLUT4 transporters in the membrane, glucose cannot enter the cell, and it simply remains in the blood. This is a primary action of insulin. Recruit GLUT4 transporters to the surface of fat and muscle cells, allowing glucose to enter the cell and reduce the amount of glucose in the blood.

This is only the beginning of the effect of insulin. We have brought glucose, single molecules of sugar, into the cell. However, this is about creating stable, usable forms of energy, so getting energy into the cell is just the first step. The cell still needs to convert these singular sugar molecules into a form of energy that can be stored long term. As we already stated, there is a deep, hardwired desire for the organism to capitalize on available energy and prepare for a day when that energy is not accessible. We convert glucose into two energy forms that are better suited for storage: glycogen and triglycerides. Glycogen is essentially a bunch of individual glucose molecules strung together, creating a single, larger molecule. This certainly helps for storage, but it also retains functionality as glycogen can be broken down into usable forms of individual glucose molecules quickly. The primary issue with glycogen is that we run out of space. Each cell can only hold so much glycogen, and when the reserves are filled up, the remainder of the glucose is used to create triglycerides. Triglycerides are the body’s best and most efficient way to store large amounts of energy. These molecules are compact, energy dense, while also retaining the ability to be broken down into usable forms of energy. Triglycerides are colloquially referred to as fat, and most of us can see the abundant stores of energy we carry around our waist.

This system of energy acquisition and storage at the cellular level is quite impressive and sophisticated. It truly highlights the body’s ability to adapt and respond to dynamic environmental conditions. But the world we live in today is much different than the world in which these systems were developed. With our basic understanding of how insulin works to pull glucose into the cell and create stable forms of energy, we will now turn to how this might be problematic in our modern life. Just as we have systems to build and store energy, we of course have systems to break down those stored forms of energy. We have processes that break down glycogen and triglycerides into molecules that can fuel our energy demanding cellular processes. However, because we have these opposing processes (anabolism versus catabolism, or storing energy versus using energy) our body has to know which protocol to run. If we are manufacturing triglycerides to store energy, it would be counterproductive if the cell next door was breaking down its triglycerides to use for energy. Once again, this is a situation our body has developed protection against. Remember what insulin’s primary message is: energy is available, grow and store energy. So not only does insulin provide a pathway for energy into the cell (GLUT4 transporter), it blocks and amplifies certain other processes inside the cell. We have discussed how insulin stimulates the building of fatty acids (energy storage in the form of fats), but the presence of insulin also blocks the cell’s ability to break down fat stores, aka insulin blocks lipolysis. This of course is the outcome of a highly intelligent system, but it certainly promotes issues for our modern lifestyle. WHEN INSULIN CONCENTRATION IS HIGH, YOU CANNOT BREAK DOWN FAT STORES. A similar process is at play with glycogen. When insulin concentration is high, the breakdown of glycogen is blocked, and the formation of glycogen is amplified. This all fits under our big picture of insulin. Insulin is a body wide signal for growth, and in turn, a body wide signal to suppress utilization of previously stored forms of energy.

Even with this basic understanding of insulin, it should be obvious that insulin levels are vitally important for anyone concerned with losing weight. As the weight we should want to lose is in the the form of triglycerides, and those triglycerides cannot be burned in the presence of high levels of insulin. I realize there is not much practical information here, or tips on how to actually utilize this information in our daily lives, but understanding this background biochemistry is fundamental to a sophisticated approach to weight loss and health in general. On this landscape we can explore how certain foods effect insulin levels, the fact that calories are NOT created equal, how movement can be leveraged to help with blood sugar control, how the timing of a meal directly affects its metabolic outcomes, how sleep is intimately connected to insulin sensitivity and glucose tolerance, and many other processes. There are so many pathways that all hinge on the metabolic control switch of insulin. Stay tuned for ideas on how to structure our lives in accordance with the biochemistry that governs our cellular processes.

Best explorations

-Ryan; 6/2/2020