digest
Intro
Hi, today we're going to talk about insulin resistance: what it is, how we can understand it, and how to treat it.
Insulin Resistance & Metabolic Syndrome
We worry about insulin resistance because it's linked to the metabolic syndrome. The metabolic syndrome is a constellation of high blood glucose, high blood pressure, abdominal obesity, and high triglycerides. Together, these really raise the risk of other diseases such as heart attacks, strokes, and cancer. Because it's such a big risk factor, we need to know what insulin resistance is and how we can treat it.
In this demonstration, we have glucose, which is shown by the yellow circle, and cells such as liver cells, which are inside the big circle. The other element is the insulin receptor. Insulin is a hormone that is naturally produced by the body, and it's produced in response to feeding. When we eat, nutrients come into our body, such as glucose, and protein can also stimulate insulin. For the most part, however, we worry about the effect on glucose, and that's what we think about when we think about insulin resistance.
In the normal situation, as we start to eat, glucose rises. The insulin then attaches to the insulin receptor, which is on the cell surface, and together this opens the doorway so that glucose can enter the cell. The cell needs this as a source of energy. When insulin is high, the receptor opens like a gate, and glucose goes in. Once that's done, the body has a source of energy. When you get to fasting, when you're not eating, insulin levels go down, and that is the signal that your body will start to use stored energy.
In this normal situation, you have a normal amount of glucose inside the cell, a functioning receptor on the surface of the cell, and a normal amount of glucose outside.
When we talk about insulin resistance, what we see is a large amount of glucose outside in the bloodstream, more than usual. This could be due to a lack of insulin, as in type 1 diabetes, but in this situation we can measure the insulin, and insulin levels are normal or usually on the high side. If insulin levels are high, you would expect glucose to go into the cell, but in the condition of insulin resistance, the glucose simply doesn't go into the cell.
What is insulin resistance?
There are really two ways to think about this. The classic way we think about what's happening is that something is blocking glucose from entering, something is causing the glucose to bounce back out. Just as a key opens a gate, we know the key is normal, which is the insulin, and we know the gate is normal, but perhaps there's a piece of gum or something within the lock that is blocking it. If that's the case, glucose piles up outside in the bloodstream, while inside the cell there is a very low level of glucose. This is sometimes called internal starvation, because there's nothing on the inside and all of it has piled up on the outside. That is the way we classically think about insulin resistance.
What is causing this insulin resistance? After 50 to 60 years, there's no real answer to that very important question.
Internal Starvation Paradigm
However, there's a problem with this internal starvation paradigm. If you think about low intracellular glucose and type 2 diabetes, type 2 diabetes is a disease where there is a lot of insulin resistance, so there should be very low levels of glucose inside the cell, and people should be very, very skinny because of this internal starvation. But that's not typically what we see in type 2 diabetes. Instead, people tend to have a lot of abdominal obesity, which is one of the components of metabolic syndrome, and we also see fatty liver all the time. So there's really no starvation that we can see.
This is the problem with the internal starvation paradigm, because it would predict that in insulin resistance and type 2 diabetes, which are essentially the same thing, there should be no fatty liver, people should be very skinny, and it shouldn't reverse with weight loss. If you lose weight and those cells give up all their fat, how would that make the insulin work better? The answer is that it doesn't. The solution proposed under this paradigm is to give more insulin, which is what we've done for many, many years. But the problem is that all of the predictions of this internal starvation paradigm are wrong.
What is type 2 Diabetes?
There is another way that glucose can pile up outside in the bloodstream and still have this insulin resistance. It may be an overflow. If you've been pushing glucose into the cell day after day, year after year, that cell may simply become overfilled, and once it is overfilled, you can't push any more glucose in. Then you see glucose piling up outside in the bloodstream. But the implication of this is very different. You wouldn't expect people to be skinny; you would expect them to be overweight, and you would expect them to have fatty liver, because it's an overflow. As you lose weight, you would expect this whole problem of insulin resistance to actually melt away, because the problem in the first place was too much glucose, which activates insulin, which pushes too much glucose inside the cell until the cell is overfilled.
Just as with a room with a door: if the door is open, people can go in, but if too many people have already gone through that door into the room, you simply can't put any more in, even with the door open. That is the overflow paradigm. The glucose does have an open door to go in, but there's already too much glucose inside the cell. As you remove some of the intracellular glucose, it should get better. So you would expect this to be reversible with weight loss, and that is precisely what we see. The solution, then, is to get rid of the glucose, not just within the blood but within the entire body. These would be fasting and low-carbohydrate diets, and weight loss. These things should in fact start to reduce insulin resistance, and recent research has shown that this is exactly what they do. The overflow paradigm seems to be a much more precise way of thinking about insulin resistance.
One final analogy: think of a subway train as the cell. Glucose should go into the cell when the doors open, and they open because of insulin. If people are piling up on the platform and unable to get onto the train, there are two possibilities. One is that the doors are simply not opening, because when insulin comes and tells them to, and inside the train there are no people. That is the internal starvation paradigm. But there's another way to think about it: perhaps there are just too many people on the train already, and no matter how much insulin tries to push people in, there simply isn't enough room. High insulin levels eventually lead to insulin resistance, and it is this overflowing that causes it. By understanding the overflow paradigm of insulin resistance, you can see that it is simply a matter of too much glucose in our bodies, not just within the blood but within our whole body.
Hyperinsulinemia
Taking a medication such as more insulin for type 2 diabetes is simply going to take the glucose in the blood and shove it into the cell that already has too much glucose. You can shove in more and more with higher and higher doses of insulin, but as you do, things get worse, because you're making the underlying situation worse. Just as if you were to cram more people into the subway train at the next stop, things will be even harder. That is exactly what we see clinically: as you give people insulin for type 2 diabetes, things don't get better over time. They take more and more insulin. When someone takes more and more insulin for type 2 diabetes, it means the disease is getting worse, and people know this because as they take insulin, they start to gain weight. Why? Because the insulin is shoving glucose into the cell, and the cell turns that into fat. As they gain weight, their type 2 diabetes gets worse and they need more insulin; as they take more insulin, they gain more weight; and as they gain more weight, they need more insulin. It's a vicious cycle that gets worse and worse.
Outro
Thanks for watching, everybody. I hope you learned something this week. If you did, you might want to check out some of these other videos on fasting, and how that might help you lose weight, get rid of fatty liver, and reverse type 2 diabetes. It's all free and available for anyone to do. I'll see you next week.