#258 – What are glucose and insulin and why do they matter for health? | Dr. Robert Lustig & Ben Grynol

Excess glucose from food gets stored as fat. And our insulin response drives that fat storage. The goal is for the pancreas to release less insulin but for the body to have a healthy response to it. Dr. Robert Lustig and Ben Grynol discuss the interplay between glucose and insulin, healthy glucose numbers, and the problems with insulin resistance.

Helpful links

• Robert Lustig, MD: https://robertlustig.com
• Robert Lustig, MD, on Instagram: https://www.instagram.com/robertlustigmd
• Robert Lustig, MD, on Twitter/X: https://x.com/RobertLustigMD

1:50 — The functions of glucose

Glucose can be used for burning or for growth

Glucose, you take it in from the outside in food, and it is substrate for both growth and burning. So you can use it to burn. You can use it to power the little energy-burning factories inside each of your cells, so mitochondria, to make energy for the cell in the form of ATP, adenosine triphosphate, which is chemical energy that your body can use to power itself. Or you can turn glucose into building blocks of the cell so that the cell can grow and the cell can divide. So glucose can be turned into lipids for membranes. It can be turned into ribose for DNA. It can be turned into proteins for structural growth. Glucose does both. The question becomes, How does the cell know which one to do at any given time. What are the control mechanisms on any given cell at any given moment?

3:04 — Glucose levels change throughout the day

From the dawn phenomenon to glucose response after a meal, your glucose is constantly changing but your levels can provide valuable insight into your metabolic health.

Your glucose changes during the course of the day.  It’s actually higher when you wake up because of growth hormone and cortisol being released while you sleep. It’s about five to seven points higher in the morning. We see this in diabetics. It’s called the dawn phenomenon. Well, the dawn phenomenon occurs in non-diabetics too because of cortisol release when you’re waking in the morning. It’s part of life.  So measuring your blood glucose at 7 a.m. is not the same thing as measuring your blood glucose at 10 p.m. In addition, catching the rise and fall as you eat gives you all sorts of information about your insulin dynamics: whether or not your beta cells are making enough insulin and whether that insulin is working properly.

4:10 — The implications of reactive hypoglycemia

Reactive hypoglycemia can drive cravings and weight gain.

When you clear your blood glucose from a meal, does the insulin hang around? Because if it hangs around, it’s going to drive your blood glucose lower than baseline. And now you have something we call “reactive hypoglycemia.” And that makes you irritable and, most importantly, hungry. And so there’s a really good chance you’re going to reach for that chocolate chip cookie. Knowing that that happens to you is enormously important in terms of metabolic health and weight loss.

7:31 — Understanding glycemic index and glycemic load

Not all carbohydrates are created equal. Some will cause a greater spike. But, as a rule of thumb, pairing fiber with carbohydrates can help blunt spikes.

Glycemic index tells us how high will your blood glucose rise in that spike when you consume 50 grams of carbohydrate in a given food.  So if you consume 50 grams of carbohydrate in bread, your glucose is going to go a lot higher than if you consume 50 grams of carbohydrate in beans. Bread: high glycemic index.  Beans: low glycemic index.  Okay, now the second thing, fiber. The amount of fiber translates into slowing of that glucose absorption. So even if it’s amylopectin,  the presence of fiber in the food will act as a barrier. It forms a gel on the inside of your intestine, preventing glucose from actually being able to get into your bloodstream. So you will actually reduce the size of the spike by the presence of fiber. This concept of using fiber to reduce the size of the spike has a name also. It’s called glycemic load.

9:52 — How many glucose spikes per day are okay?

Eating causes a natural glucose rise, but the goal is to blunt peaks.

How many spikes are acceptable per day? And the answer is: however many meals you eat. That’s how many are acceptable because you’re going to get a spike every time you put food in your stomach. The question is, To what extent? The goal is to mitigate that spike as much as possible. If you eat foods that are low in refined carbohydrate, high in fiber, and low in leucine, then you should be able to keep your glucose spike, and therefore your insulin spike, relatively low.

13:14 — Insulin drives fat storage

Insulin stimulates fat cells to uptake glucose. Eating more glucose than your brain, organs, muscle, etc., need will lead to fat storage.

The only cell that needs insulin to import that glucose is your fat cell. So whatever’s left over the insulin will clear and put into the fat cell for storage because the rest of the body doesn’t need the insulin to extract the glucose from the bloodstream. So a glucose spike, in essence, is your body’s attempt to clear your meal. Every organ in your body will take what it needs, and only the fat cell will get the rest, and it gets that from insulin. The higher the spike, the more your rest of your body didn’t get it. So the goal is to keep the spikes low so that the rest of the body doesn’t need the insulin in order to clear it.

16:21 — How glucose spikes do their damage

Frequent and outsized glucose spikes can lead to insulin resistance.

When you consume a meal, you’re going to overwhelm your body’s blood glucose. It has to be cleared. So your pancreas is going to make insulin. The insulin rise is going to clear that glucose. The question is, How much can you make and how quick does it work? The goal is: don’t make so much and have it work great. The problem is, as you get older, as you get less fit, you’re going to have to clear that glucose, and your beta cells may not be able to make enough. In which case, you’re not going to clear that glucose very quickly. And so the blood glucose will rise, so you will have a big glucose spike. And that will do damage to your vascular system. And, as you get less fit, your insulin will work less well to drive that glucose out of your bloodstream. And that will mean that the glucose stays elevated for longer. That phenomenon of insulin not working as well we call “insulin resistance.”

18:43 — How eating late before bed can cause insulin resistance

Maintain at least a four-hour buffer between dinner and bedtime to help prevent insulin resistance

There should be at least four hours between the time you eat dinner and the time you go to sleep. If you’re eating with less time between dinner and bedtime, then your glucose is going to be high. And that’s going to end up driving energy into fat while you’re sleeping because the glucose still has to be cleared. And that’s going to generate more insulin resistance, and that’s going to show up throughout the entire day as a higher baseline.

20:52 — A look at healthy glucose levels

Glucose should not stay high for long and it shouldn’t drop below your baseline.

We now have a fair amount of data. What we’ve learned is that in response to a mixed meal—because that’s what people eat, they don’t just consume glucose—what we’ve seen is that the rise will occur within the first 30 to 45 minutes. And it should fall again around 75 to 90 minutes. If your blood glucose has returned to baseline by 90 minutes, you are doing pretty well. If, on the other hand, it is still high at 120 minutes, you are not doing as well. And the other thing you need to watch for is this reactive hypoglycemia. And that tends to center around 75 minutes. So if your blood glucose goes below baseline at 75 minutes, check to see how you feel. When you get that number, see if that is below baseline and see if you feel irritable, tired, hungry. Because if that’s the case, that means that your insulin response is greater than your need. Because it is sticking around and driving your glucose lower. Which means you probably need a change in the carbohydrate or the fiber you’re eating.

25:46  — Insulin resistance is the first sign of issues

Mitochondria are the powerhouse of cells. When they’re dysfunctional, it shows up as insulin resistance.

Mitochondrial dysfunction translates into insulin resistance. Insulin resistance translates into hyperinsulinemia. Hyperinsulinemia translates into  chronic metabolic disease. So you can draw a direct line between the mitochondria and your health. Insulin resistance is the first sign of the problem.

[00:00:00] So a glucose spike in essence is your body’s attempt To clear your meal and every organ in your body will take what it needs and Only the fat cell will get the rest and it gets that from insulin the higher the spike The more your rest of your body didn’t get it So the goal is keep the spikes low so that the rest of the body doesn’t need the insulin in order to clear it.

[00:00:39] Ben: So in February of 2024, Dr. Robert Lustig and I found ourselves sitting across from each other in Los Angeles. We had planned to sit down and have a little chat about metabolic health and some of the implications around lifestyle, sleep, exercise, all these pillars of metabolic health. When we ended up sitting for six hours, we had a really deep conversation and we covered a number of topics.

[00:01:06] Ben: The idea was that we were filming some videos, some short form videos, which would be helpful for Levels members and anyone interested in metabolic health generally to get more insight into some snippets, some takeaways of what they could think about certain categories of metabolic health. Well, we decided to cut these into a podcast as well.

[00:01:26] Ben: So we’ve got a number of topics and we thought, why don’t we categorize them and people can pick and choose what they want to listen to. So lots of good information, lots of soundbites here, but we stitched them together into these different categories. So, there’s some transitions, but it might be something that is of interest.

[00:01:43] Ben: So the idea is always, I hope it helps people to learn more, to take metabolic health into their own hands So in this episode, Rob covers glucose. A number of things related to glucose. Glucose spikes, variability, circulation, spike frequency, shape and duration, things like meal consumption and metabolic health, timing of meals and how that impacts glucose variability.

[00:02:07] Ben: Even things like hormone response to glucose spikes. He covers hyperglycemia and hypoglycemia. And even things around mitigating glucose spikes. What can people do to make some of those changes? Gives a little bit of insight around fasting glucose and glucose level guidance.

[00:02:24] Ben: And then gives an overview of glucose monitors and metabolic dysfunction. for your attention.

[00:02:29] Glucose, you take it in from the outside in food and it is substrate for both growth and burning. You can use it to burn, you can use it to power the little energy burning factories inside each of your cells, the mitochondria, to make energy for the cell in the form of ATP, adenosine triphosphate, which is chemical energy that your body can use to burn.

[00:03:00] to power itself, or you can turn glucose into building blocks of the cell so that the cell can grow and the cell can divide. So glucose can be turned into lipids, for membranes, it can be turned into ribose for DNA, it can be turned into proteins for structural growth. Glucose does both. The question becomes, how does a cell know which one to do at any given time?

[00:03:36] What are the control mechanisms on any given cell at any moment?

[00:03:43] Your glucose changes during the course of the day. It’s actually higher when you wake up because of growth hormone and cortisol being released while you sleep. It’s about five to seven points higher in the morning. We see this in diabetics. It’s called the dawn phenomenon. Well, the dawn phenomenon occurs in non diabetics too because cortisol release when you’re waking in the morning.

[00:04:15] It’s part of life. So, measuring your blood glucose at 7 a. m. is not the same thing as measuring your blood glucose at 10 p. m. In addition, catching the rise and fall as you eat gives you all sorts of information about your insulin dynamics. Whether or not your beta cells are making enough insulin, and whether that insulin is working properly.

[00:04:45] And lastly, something else that’s super important. When you clear your blood glucose from a meal, does the insulin hang around? Because if it hangs around, it’s going to drive your blood glucose lower than baseline. And now you have something we call reactive hypoglycemia. And that makes you irritable and most importantly hungry.

[00:05:15] And so there’s a really good chance you’re going to reach for that chocolate chip cookie. Knowing that that happens to you is enormously important in terms of metabolic health and weight loss.

[00:05:30] The glucose spike is due to your food. Air pollution doesn’t cause a glucose spike. But the kind of food will determine the degree of the spike. And there are two reasons. One is the kind of glucose. And the other is the amount of fiber. So let’s take each one individually. The kind of glucose. I just told you, glucose is glucose.

[00:06:05] But, in fact, polymerized glucose, called starch, has two forms. One is bread, rice, pasta, potatoes, called amylopectin. And the other one is beans, lentils, other legumes, called amylose. Amylopectin, amylose, they are not the same. Amylose, the brown food, if you will. Is a string of glucoses. One end, one end, and the string is put together by bonds between the glucose molecules called alpha one four bonds, alpha one four bonds.

[00:06:54] They end up giving you a glucose response that is lower and slower amylopectin. is branched. It’s not a string. It’s got branches. It’s got alpha one, four bonds, but it also has alpha one, six bonds. It looks like a Christmas tree. And so enzymes can basically Digest different glucoses off the tree, and so you can generate a much bigger and more rapid glucose response in your intestine, and therefore you will absorb more glucose faster.

[00:07:34] It will give you a bigger rise. Well, a bigger glucose rise ultimately means a bigger insulin rise, too. So amylose has been shown to work. to have beneficial effects in terms of keeping your insulin down. Amylopectin has been shown to increase the risk for an insulin rise. Now this is captured through a phenomenon which we call the in nutrition called glycemic index.

[00:08:10] Glycemic index tells us how high will your blood glucose rise in that spike when you consume 50 grams of carbohydrate in a given food. So if you consume 50 grams of carbohydrate in bread, your glucose is going to go a lot higher than if you consume 50 grams of carbohydrate in beans. Bread, high glycemic index.

[00:08:39] Beans, low glycemic index. Okay, now the second thing, fiber. The amount of fiber translates into slowing of that glucose absorption. So even if it’s amylopectin, the presence of fiber in the food will act as a barrier. It forms a gel on the inside of your intestine, preventing glucose from actually being able to get into your bloodstream.

[00:09:11] So you will actually reduce the size of the spike. by the presence of fiber. This concept of using fiber to reduce the size of the spike has a name also. It’s called glycemic load. An example of this would be carrots. So carrots have a high glycemic index. If you eat 50 grams of carbohydrate in carrots, Your blood glucose will go pretty high.

[00:09:40] But the question is not, what is the glycemic index of carrots? The question is, what is the glycemic load of carrots? Because, in order to get 50 grams of carbohydrate in carrots, you have to eat 700 grams of carrots. You have to eat 1. 4 pounds of carrots. Now, aside from Bugs Bunny, who’s doing that? Nobody.

[00:10:02] And that’s the point. So even though carrots have a high glycemic index, it has a low glycemic load. So amylose fiber, both of them control the size of the glucose spike. And when you control the glucose spike, you’re controlling the insulin spike. And when you control both of those, you are contributing to metabolic health.

[00:10:32] How many spikes are acceptable per day? And the answer is, however many meals you eat. That’s how many are acceptable because you’re going to get a spike every time you put food in your stomach. The question is, to what extent? The goal is to mitigate that spike as much as possible. If you eat foods that are low in refined carbohydrate, high in fiber, and low in leucine, then you should be able to keep your glucose spike, and therefore your insulin spike, relatively low.

[00:11:16] Optimally, you should probably only eat two meals a day, maybe three meals a day if you’ve A family, and, you know, you need it. Probably two meals a day will do it. We, in America, tend to eat three. And is that part of the reason we have metabolic dysfunction? I don’t think so. Some people have postulated that we don’t need that third meal.

[00:11:44] Maybe we don’t need that third glucose spike. Hard to know. We don’t have good controls to answer the question. Ultimately, I don’t care how many spikes you have. As long as you do whatever you can to mitigate the amplitude of the spike and the duration of the plateau. In other words, improve insulin release and improve insulin sensitivity.

[00:12:13] Get the insulin down any way you can.

[00:12:17] Glucose is the energy of life. Glucose is part of sugar. It’s part of starch. It’s everywhere around us because every cell on the planet burns glucose for energy. Now you eat a meal, you get a glucose load. That glucose gets absorbed from your intestine and goes straight to the liver. The liver takes about 20 percent of that glucose load and imports it into the liver directly.

[00:12:58] That leaves about 80 percent of the glucose out in the bloodstream to circulate and that raises the serum glucose. You can measure that. You can measure it with finger sticks. You can measure it with a CGM. The point is, that glucose load is supplying the serum. substrate for either growth or burning to the rest of the body.

[00:13:28] 20 percent is going to your brain and the rest is going to your heart, your kidneys, your muscles, any other organ that needs energy, which is all of them. That will raise your serum glucose, which you can measure. The cells will extract the glucose they need. The only cell that needs insulin to import that glucose is your fat cell.

[00:14:03] So whatever’s left over the insulin will clear and put into the fat cell for storage because the rest of the body doesn’t need the insulin to extract the glucose from the bloodstream. So a glucose spike in essence is your body’s attempt To clear your meal and every organ in your body will take what it needs and Only the fat cell will get the rest and it gets that from insulin the higher the spike The more your rest of your body didn’t get it So the goal is keep the spikes low so that the rest of the body doesn’t need the insulin in order to clear it.

[00:15:00] There’s different information in the different components of the spike. It’s not that the spike is worse than the plateau. It’s not that the plateau is worse than the spike. They’re telling you different things. The size, the amplitude of the initial spike is telling you what your insulin reserve is. So people with reduced insulin secretory capacity are going to have a bigger spike.

[00:15:33] than people who can muster up a bigger insulin response. The plateau is going to tell you how insulin resistant are you, and that’s going to tell you about your risk for all the other diseases of high insulin. term metabolic syndrome. So not just diabetes, but fatty liver disease, um, hypertension, uh, dyslipidemia, uh, cardiovascular disease, cancer, dementia, uh, polycystic ovarian disease are all dependent on that plateau.

[00:16:14] And what we’ve learned is that the spike as the resistance gets worse and your beta cell starts running out of insulin, then the spike goes up. So in a sense, the plateau tends to precede the spike in terms of the evolution of the disease. So it’s not really a question of which is worse. It’s more of a question of what comes first.

[00:16:42] Eventually, if you’ve got a defective plateau because you’re not clearing insulin, that means your beta cell is under strain and ultimately it will show up as a big spike at the beginning and both are bad.

[00:17:01] When you consume a meal, you’re going to overwhelm your body’s blood glucose. It has to be cleared. So your pancreas is going to make insulin. The insulin rise is going to clear that glucose. The question is, how much can you make and how quick does it work? The goal is, don’t make so much and have it work great.

[00:17:31] The problem is, as you get older, as you get less fit, You’re going to have to clear that glucose, and your beta cells may not be able to make enough. In which case, you’re not going to clear that glucose very quickly. And so the blood glucose will rise, so you will have a big glucose spike. And that will do damage to your vascular system.

[00:18:01] And, as you get less fit, your insulin will work less well to drive that glucose out of your bloodstream. And that will mean that the glucose stays elevated for longer. That phenomenon of insulin not working as well, we call insulin resistance. Two different phenomena. Insulin release can be compromised, And that will give you a high glucose spike, or insulin resistance, that will give you a long glucose plateau.

[00:18:38] Both are signs of metabolic dysfunction. Both lead to illness and death.

[00:18:48] Some people see that their blood glucose is lower in the morning and higher in the evening. You’d expect it to be the other way around. That may be due to changes in diurnal rhythms. It may be due to the food. If you are eating a high carbohydrate diet, then there’s a very good chance that you are priming your beta cell as the day goes on, and so you’re getting a bigger glucose spike.

[00:19:18] And because you’re eating late, Instead of early, you should, there should be at least four hours between the time you eat dinner and the time you go to sleep. If you’re eating with less time between dinner and bedtime, then your glucose is going to be high, and that’s going to end up driving your sleep.

[00:19:39] Uh, energy into fat while you’re sleeping because the glucose still has to be cleared and that’s going to generate more insulin resistance and that’s going to show up throughout the entire day as a higher baseline. But in particular because of the high carbohydrate meals, you will see a higher glucose at the end of the day.

[00:20:02] When you eat, your blood glucose rises. When the blood glucose clears, if your blood glucose goes below baseline, you kick out three hormones in order to raise your blood glucose back again. You kick out glucagon, you kick out epinephrine, and you kick out cortisol. All to make your blood glucose come back to baseline.

[00:20:37] The problem is, you also got irritable and hungry. And so you eat on top of that. And so you’ve got these three hormones generating a glucose rise at the same time. You’re trying to fix it with food, and so you get a bigger response, which then the insulin will come and knock back down, and you may yet get another reactive hypoglycemia again, and so you may kick your glucagon, your epinephrine, and your cortisol back in a second time, and so now you have a glucose rollercoaster.

[00:21:18] Because of the counter regulatory hormones. That your body made in response to your glucose going down below baseline, all because of the food you ate.

[00:21:32] We now have a fair amount of data, and what we’ve learned is that in response to a mixed meal, because that’s what people eat, they don’t just consume glucose. What we’ve seen is that the rise will occur within the first 30 to 45 minutes. And it should fall again around 75 to 90 minutes. If your blood glucose has returned to baseline by 90 minutes, you are doing pretty well.

[00:22:04] If, on the other hand, it is still high at 120 minutes, You are not doing as well. And the other thing you need to watch for is this reactive hypoglycemia. And that tends to center around 75 minutes. So if your blood glucose goes below baseline at 75 minutes, check to see how you feel. When that, when you get that number and see if that is below baseline and see if you feel irritable, tired, hungry.

[00:22:38] Because if that’s the case, that means that your insulin response is greater than your need. Because it is sticking around and driving your glucose lower. Which means you probably need a change in the carbohydrate or the fiber you’re eating.

[00:22:56] So remember, there are two parts to the insulin excursion. There’s the initial rise or the spike, and then there’s the second phase or the plateau. That rise can be mitigated by reducing total carbohydrate and increasing fiber. The plateau can be mitigated by improving insulin sensitivity. That is reducing refined carbohydrate and sugar.

[00:23:29] Either way. Fixing your diet will fix the insulin excursion, both parts of it, the spike and the plateau. Get the sugar down, get the carbohydrate down, get the insulin down. And you will improve metabolic health, you will improve mitochondrial functioning, you will improve your health and your longevity.

[00:23:55] TRANSITION

[00:23:56] So what should your average glucose level be? The fact is, there is no average level of glucose because it’s in constant fluctuation. Because you’re always either pre prandial or post prandial. Except when you’re asleep. Now, when you’re asleep, your average glucose should be somewhere between 60 and 80.

[00:24:17] When you’re awake, it kind of depends on what you’re doing, and it also depends on what you’re eating, and it depends on how insulin sensitive you are, and it depends on how much stress you’re under, and it depends on the last cup of coffee you drank. So, it’s actually kind of hard to get specific numbers.

[00:24:36] Having said that The American Diabetes Association says that if your fasting blood glucose is over 90, it’s an issue. If it’s over 100, you have prediabetes. And if it’s over 125, you actually have type 2 diabetes. If your postprandial, 2 hour postprandial blood sugar is over 140, you have prediabetes. And if your blood, postprandial blood sugar is over 200, you have frank type 2 diabetes.

[00:25:08] What I care about is you getting your blood glucose as low as possible because you got your insulin back. As low as possible. If you become insulin sensitive, your glucose will take care of itself. That’s where you start. And to be honest with you, that’s where you finish. But how do you get there? CGM is the best way today to get there.

[00:25:38] So what should your fasting glucose be? Well, it should be probably between 70 and 85 optimally, maybe 70 to 90 suboptimally. How high should it go after you’ve eaten? Probably shouldn’t go above 110. If it goes above 120 and turns around quickly, not so bad. Ultimately, the goal is to get back to baseline within 90 minutes.

[00:26:11] That’s more important than how high it goes because that’s the plateau. If you’re seeing it go further than that, that’s the sign of insulin resistance that tells you you’ve got metabolic dysfunction.

[00:26:26] Mitochondrial dysfunction translates into insulin resistance. Insulin resistance translates into hyperinsulinemia. Hyperinsulinemia translates into chronic metabolic disease. So you can draw a direct line between the mitochondria and your health. Insulin resistance is the first sign of the problem.

[00:26:56] That’s telling you you’ve got a problem. You can see it in the plateau. Mitochondrial Eventually, you’ll see it in the fasting insulin. So, without question, a continuous glucose monitor will pick up metabolic dysfunction before any of our other hormones. That’s laboratory biomarkers do. One of the reasons for choosing and wearing a continuous glucose monitor is to look at that insulin plateau, cause that is the first sign your metabolism has a problem, that things are going south.

[00:27:36] Insulin drives defective cell growth. It causes cells to grow when they shouldn’t. It certainly causes fat cells to grow. But it also causes vascular smooth muscle to grow, it causes glandular tissue to grow, it causes changes in the brain that prevent utilization of glucose because of insulin resistance, which ultimately lead to defective ATP generation.

[00:28:11] That’s one of the reasons why Alzheimer’s disease has been called diabetes type 3. But, you know, we know that insulin resistance is a primary driver. of defective CNS glucose utilization. So getting your insulin down is job one. It is the most important thing to improve your metabolic health and continuous glucose monitoring.

[00:28:40] We’ll pick up the first signs of that metabolic dysfunction before any of our other biomarkers can. So that’s where the rubber hits the road.