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Metabolic Flexibility – Part 2 Insulin Resistance

Metabolic flexibility is the ability of systems supporting the human body to balance the supply of incoming and stored energy with the demands of the body, given:

  1. A variety of fuel sources (fatty acids, sugars, protein, ketones, etc.) and
  2. Dynamic metabolic demands (sedentary vs. low-intensity vs. high-intensity activity; fasting vs. fed state)

We can think of this, simply, as the ability for tissues throughout the body to efficiently switch back and forth between managing one fuel source or another. Eat a load of carbohydrate? No problem, the body will shift its attention to managing this fuel source right away. Eat a load of fat? No problem, the body will use this as a fuel source to meet its metabolic demands when blood sugar is not elevated.

Two important questions to understand are how the body manages all of this, and what happens if it can’t?

The short answer – there are numerous mechanisms at work that combine to establish the metabolic flexibility of a particular tissue, organ, or organ system. With this post, we will focus in on one key mechanism: insulin sensitivity, and its counterpart, insulin resistance.

This is a topic that we walked through from a high-level view in last week’s post as one piece of the big picture that is the progression of poor health and modern disease. This week, the goal is to put our full attention on insulin, along with the actions we can take to better manage it and our tissue’s ability to respond to it in the most efficient way possible.

Insulin – A Quick Overview
Insulin is one of the body’s key energy regulation signals. In response to elevated blood sugar, the pancreas releases insulin as a signal to cells throughout the entire body to work in their own specific way in a collective effort to lower blood sugar.

In an insulin-sensitive individual, the pancreas will release a small amount of insulin, and tissues (as collections of cells) throughout the body will quickly respond:

  • Skeletal Muscle – the body’s primary means of taking up elevated glucose from the bloodstream. Skeletal muscle responds to the insulin signal by taking in glucose and either storing it as glycogen or utilizing it to synthesize ATP.
  • Liver – the body’s master metabolic regulator; it continuously senses the body’s supply of energy (e.g., sensing glucose and insulin levels in the bloodstream), and in turn, meets the needs of the body by storing or releasing energy from its own stores or by converting one fuel source to another.
  • Adipose tissue – the body’s primary site of energy storage. It takes in both lipids and glucose and stores it all as fat. This fat can then be released as fatty acids into the bloodstream to be utilized as a fuel source by other tissues and organs.
Figure 1: The elevation of insulin (in response to rising blood glucose levels) shifts the metabolic focus of various tissues, all in an effort to lower blood glucose levels. Each specific tissue will act given its own specialized function to achieve this goal.

When these tissues are sensitive to the insulin signal, they work together in a complex network to balance out the supply and demand of each fuel source. For example, if blood sugar is elevated, skeletal muscle will take in most of this excess and store it as glycogen while the liver simultaneously takes it in, storing some as glycogen and converting any excess to fat to be shipped out into the bloodstream. If blood sugar drops, the liver will release glucose into the bloodstream from its glycogen stores. Meanwhile, adipose tissue is constantly taking in glucose and lipids or releasing its stored lipid – all depending on the signals it itself is receiving.

Figure 2: In an insulin-sensitive individual, the pancreas releases a small amount of insulin in response to elevated blood sugar. Tissues throughout the body respond by performing their own specific functions in a collective effort to lower blood sugar: the muscle will store away glucose as glycogen and will switch from oxidizing fats as a fuel source and instead oxidize glucose; the liver will store away glucose as glycogen and convert any excess glucose to fat to be shipped back out into circulation; adipose tissue will take in both fats and glucose and store them away as fat

When these tissues are all insulin sensitive, the body can maintain a healthy balance. Following a carbohydrate-rich meal, energy will get stored away as both fat and glycogen build-up in storage. Then, when blood sugar concentration drops back down and the insulin signal recedes, fat can be released from storage in adipose tissue and glucose can be released from stored glycogen. In this way, tissues throughout the body have a constant supply of energy and the bloodstream is never over-burdened with hyperlipidemia (elevated blood lipids) or hyperglycemia (elevated blood sugar).

However, if these tissues do not quickly and effectively respond to this insulin signal, then the entire body is at risk due, in particular, to that elevated blood sugar. This risk can vary from rather low and only relevant over many years (glycation of proteins by glucose, rendering them useless or dysfunctional) to severe and immediate (seizure/death).

Because elevated blood sugar can be a life-threatening situation, nature has created us humans with a mechanism for overcoming it: quite simply, the pancreas releases more insulin.

Figure 3: If a tissue (muscle, for example) becomes insulin-resistant, then blood sugar concentration will elevate. In response, the pancreas releases even more insulin, sending a stronger signal to store energy. This will lead to the continued synthesis of fat by the liver and drive more energy into storage as fat.

We saw in last week’s post how this is part of a vicious cycle, wherein hyperinsulinemia drives excess fat accumulation as it puts the body in a state in which:
1. The bulk flow of energy (especially fat) is driven into storage and
2. Fat oxidation is brought to a halt

This is not a situation we individuals want to be in for a number of reasons, which can be perceived:
1. Day-to-day, felt as low and/or unstable energy.
2. Over months to years, as the cycle often involves the accumulation of excess fat
3. Over years, the cycle progresses to the development of a large number of clinically relevant symptoms, at which point we give the problem a name (cardiovascular disease, type II diabetes, cancer, Alzheimer’s disease), and begin to treat the life-threatening symptoms.

This is not the fate I want for any individual. I do not want anyone to suffer through the decline in life that comes with the progression of insulin resistance – beginning with low, unstable energy and weight gain and, down the road, leading to the arising of life-threatening symptoms. This is why I am so happy you are here to pay attention so that you can gain the knowledge you need to avoid (or even reverse) this cycle.

Let’s spend the rest of this article talking about actions you can take to do so.

How to address insulin resistance in our own lives
Before getting too deep into this topic, I want to begin by giving you one clear solution that you have the option to engage in every single day to improve your insulin sensitivity. Next week, I will dive into this particular practice in much greater depth, but I don’t want to leave you hanging without this practical advice until then.

So, what’s the one thing that you can do every day, starting today, to enhance your body’s overall insulin sensitivity?

The answer – Exercise!

If there is one thing that we know which immediately and effectively improves insulin sensitivity, it is to move your body: to take it out for a walk, or maybe even a run, every single day; to put it under a strong load of physical stress (lift weights, sprint) a few times each week.

When we put the systems supporting our body to use:
– When we put our muscles to work in an endurance or strength effort…
– When we send a signal to adipose tissue to release its stored fat…

… when we use the machinery within our bodies and when we use the energy stored within, then this machinery maintains (or even improves upon) its ability to function.

This is one of the remarkable features of living life as a biological being: the body that you have has the ability to improve, when you use it. So, this is the simplest advice I can give to you right now: use your body the way it was intended and go move!

Now, what I do wish to dive into depth with today is the dietary side of insulin sensitivity. However, before we dive in, there’s something I have to explain that has everything we do with how we approach the solution to this problem.

For a while now, there has been a mountain of information piling up surrounding which dietary components enhance or harm the body’s insulin sensitivity. There seems to be an endless stream of research coming in, and while there is much that can be learned here, there are a number of problems with this pile of information:

  • First, there is a lot of it. You could spend months digging through the information to try to find answers to what it is you should do.
  • Second, if you were to take this challenge on, what you would find is that much of this information is conflicting – that is, what one study would seem to be recommending does not necessarily align with what another study says. Heck, sometimes, the information seems to be saying the exact opposite.

This is exactly what I did several years ago when I asked the question “What is the healthiest diet” and spent the following years searching for the answer. Because I don’t want you to think you need to do this, I am going to walk you through my conclusions so that you can see for yourself what it means to eat a healthy diet, one that supports insulin-sensitive tissues. I will present a small sample of the data so that you can begin to see the problem for yourself, and from there we can step back and think about what we may want to choose in our own lives.

The traditional, reductionist approach provides us with all the information we could ever want regarding what specific nutrients do to a tissue’s insulin sensitivity. Let’s look at a selection of specific studies examining specific nutrients and their impact on insulin sensitivity:

This first study asks the question of what is the impact of protein vs. carbohydrate on insulin sensitivity? (1) Their findings: A high-carb diet enhanced insulin sensitivity while a high protein diet impaired it:

  • (+) High carb diet
  • (-) High protein diet

This second study asks the question of what is the impact of different types of fatty acids on insulin sensitivity? (2) Their findings: Increasing unsaturated fat enhanced insulin sensitivity while saturated fat slightly decreased it.

Figure 4: Insulin sensitivity is enhanced by monounsaturated and polyunsaturated fat (ref 2)
  • (+) monounsaturated and polyunsaturated fat
  • (-) saturated fat

Looking at these simple messages presented by each of these studies may lead us to make specific decisions in our own lives:

  • choose more carbohydrate
  • avoid saturated fat and consume more unsaturated fat

Which sounds simple enough, until we keep digging.

This third study – a review of 102 studies – asks the question of what is the impact of different types of macronutrients on insulin sensitivity? Their conclusion: “substituting carbohydrate and saturated fat with a diet rich in unsaturated fat, particularly polyunsaturated fat, was beneficial for the regulation of blood sugar”

  • (+) unsaturated fat
  • (-) saturated fat and carbohydrate

Their conclusion, once again, seems like a clear and simple message. But what does their data really indicate? Well, it really depends on the specific study, as shown below:

Figure 5: How to look at this image: each vertical line represents baseline for a particular exchange of one macronutrient for another. A shift to the left represents lowered (and therefore improved) fasting insulin. A shift to the right represents an elevation in fasting insulin (ref 3)

What we can see from representations of large amounts of data is that there are general trends that tend to be consistent, although there is also a great amount of variability and some inconsistent results.

Let’s dig into some of these inconsistencies with the saturated fat example. All of the above papers would seem to indicate that consuming saturated fat is an unhealthy decision when it comes to insulin sensitivity. But what about this study (4) that asked a very specific question: what happens when we decrease carbohydrate consumption and increase fat consumption in a step-wise manner? This study found some very clear results that don’t necessarily line up with the previous studies – results indicating the benefit of swapping out carbohydrate and instead consuming more fat.

Figure 6: decreasing carbohydrate consumption and increasing fat consumption results in a significant improvement in insulin sensitivity (ref 4)

Which leaves us all with a very important question: given the large amount of conflicting studies that seem to indicate different ideas of what a “healthy” decision is in regards to insulin sensitivity, what are the specific decisions that we should make each time we buy groceries or prepare a meal?

Do we:

  1. Choose the salad with dressing made of unsaturated fat and sugar?
  2. Do we add meat to that salad? What kind of meat – red or white?
  3. Do we choose a sandwich instead? Is that bread okay? Do we put meat on that sandwich or keep it vegetarian?

The answer based on the reductionist approach: well, it depends on the exact study you wish to call out and the exact conclusions drawn from each.

And when these conclusions counteract one another, what do we do then?

This is a significant problem, which is exactly why I took the time to sift through the information myself, combining information from these studies with my knowledge of the progression of insulin resistance, all to come up with what I believe is a better solution. This solution takes into account the complex, dynamic system that is the human body and its interaction with the environment (via the individual’s decisions), appreciating the interplay that is an individual’s specific lifestyle and decisions and their impact on the current state of their physiology.

Let’s take a look at that solution now.

The Reprogrammed Systems Approach:

The key point that we should wish to focus our attention on is, What is the healthy decision for our own bodies? Today, we ask the specific question that is, What is the healthy decision that enhances the insulin sensitivity of the tissues supporting our own bodies?

Note that the answer to this question is not necessarily what a particular study says is the positive outcome in that particular study; instead, the important question for each individual is, What is the decision that will lead to their own healthier body? And for the purposes of this article, we dial in this question and ask, What is the decision that will lead to enhanced insulin sensitivity of the tissues supporting the body?

To answer this question, let’s take a step back and think about the big picture that is the progression of insulin resistance. While there are a number of problems involved with the progression of this pathophysiologic state, there is one key feature of this complex system that comes to my mind:

Hyperinsulinemia is the mechanism driving the continuous build-up of fat. Remember, insulin not only tells the body to store fat, it also tells the muscle to stop oxidizing fat. When insulin is elevated in excess, the body is put in a state in which fat can not be oxidized and instead is driven into storage:

  • As this fat builds up in excess, tissues respond by becoming insulin-resistant
  • As tissues become insulin-resistant, the pancreas releases even more insulin

So, if we want to make decisions that lead to improved insulin sensitivity, we can:

  1. Decrease the need for the body to release insulin – that is, decrease the overall load of insulin that needs to be released.
  2. Ensure that when the body needs to release insulin, it is doing so in a healthy manner – that is, the dynamics of insulin release follow a healthy pattern.

Fortunately, when it comes to exactly what this means for the individual, there is a clear solution:

  1. Consume foods that minimize the release of insulin
  2. Consume foods that may release insulin, but do so in a controlled manner

That is, consume real, whole foods: foods that enter the body packaged in a complex form – a form that the body unpackages slowly, releasing contents slowly and sorting out what enters the bloodstream from what continues down the digestive tract.

Remember, this is in contrast to industrial not-so-foods – foods made of industrially processed ingredients containing concentrated forms of energy. These not-so-foods are not packaged in a complex form, and instead enter the digestive tract only to be unpacked in a fast, uncontrolled manner, releasing a large load of energy into the bloodstream.

If we can begin by shifting our diets away from not-so-foods that dump glucose and fats into the bloodstream, spiking insulin and initiating insulin-spiking and chronic fat storage… and, if we can instead consume foods that release lower amounts of glucose in a slower, more controlled fashion, then we are well on our way to managing hyperinsulinemia.

Oh, and let’s not forget – an option that is always there for you to enhance your insulin sensitivity is to go move your body! Take action that tells your metabolic machinery to get to work and burn through that stored energy.

That’s what we’ll be diving into in-depth next week, along with some additional actions you can take to improve your metabolic flexibility.

A final note:

Before closing today, I want to take our attention back to those studies mentioned earlier. If my recommendation is to start by forgetting the load of individual studies and instead focus on the bigger picture, then what are we to do about all that information? Should we just ignore it, or is there a way that we can make it useful to us?

I’m glad you asked, because it seems unwise to completely ignore this load of potentially useful information. This information will come back into play later on as the second important piece of The Reprogrammed Systems Approach. Once we have first established the basics of healthy decision-making in our own lives…

  • a diet based on real, whole foods
  • regular and dynamic movement
  • a balance of stress and rest

… once these foundational practices have been established, then it may be time to dive into the literature and work to more finely tune our own specific diets.

However, that is a practice for another day. Until then, stay focused on the simple, obvious strategies above that will most likely take you leaps and bounds towards a life of good health.

References

  1. Martin O Weickert, Michael Roden, Frank Isken, Daniela Hoffmann, Peter Nowotny, Martin Osterhoff, Michael Blaut, Carl Alpert, Özlem Gögebakan, Christiane Bumke-Vogt, Friederike Mueller, Jürgen Machann, Tom M Barber, Klaus J Petzke, Johannes Hierholzer, Silke Hornemann, Michael Kruse, Anne-Kathrin Illner, Angela Kohl, Christian V Loeffelholz, Ayman M Arafat, Matthias Möhlig, Andreas FH Pfeiffer, Effects of supplemented isoenergetic diets differing in cereal fiber and protein content on insulin sensitivity in overweight humans, The American Journal of Clinical Nutrition, Volume 94, Issue 2, August 2011, Pages 459–471, https://doi.org/10.3945/ajcn.110.004374
  2. Giacca, C. X. A., & Lewis, A. C. G. F. (2006). Differential effects of monounsaturated , polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion , sensitivity and clearance in overweight and obese , non-diabetic humans. 1371–1379. https://doi.org/10.1007/s00125-006-0211-x
  3. Giacca, C. X. A., & Lewis, A. C. G. F. (2006). Differential effects of monounsaturated , polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion , sensitivity and clearance in overweight and obese , non-diabetic humans. 1371–1379. https://doi.org/10.1007/s00125-006-0211-x
  4. Volk, B. M., Kunces, L. J., Freidenreich, D. J., Kupchak, B. R., Saenz, C., Artistizabal, J. C., … Volek, J. S. (2014). Effects of step-wise increases in dietary carbohydrate on circulating saturated fatty acids and palmitoleic acid in adults with metabolic syndrome. PLoS ONE, 9(11), 1–16. https://doi.org/10.1371/journal.pone.0113605
  5. Volek, J. S., & Feinman, R. D. (2005). Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutrition and Metabolism, 2, 1–17. https://doi.org/10.1186/1743-7075-2-31

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