Published November 29, 2022
537 million people worldwide suffer from diabetes, and another 541 million suffer from prediabetes. That means that of every 10 adults worldwide, more than 2 have either diabetes or prediabetes.
There is a lot of poor or misleading information out here on the internet on blood sugar regulation, insulin resistance, and diabetes. So my goal with this blog post is to make sure you fully understand exactly how our bodies regulate our blood sugar levels, what goes wrong with this process when we develop diabetes, and how diabetes is diagnosed.
We are starting with the very basics: carbohydrates.
The basic building blocks of carbohydrates are simple sugars, sometimes also called monosaccharides. The term saccharide simply means sugar, and mono means one. So, the word monosaccharide describes carbs with one sugar molecule.
The most important monosaccharides are glucose, fructose, and galactose. As simple sugar molecules, we find glucose and fructose in fruit, honey or high-fructose corn syrup. When we eat food with simple sugars, our body can absorb these into our bloodstream without any need for digestion.
Simple sugars can also combine to form more complex carbohydrates.
For example, one glucose molecule and one fructose molecule bound together form sucrose, commonly called table sugar. Because this now has two of these simple sugars bound to each other, we call this a disaccharide. Di stands for two, so a disaccharide is a carbohydrate made from two simple sugar molecules. Another example of a disaccharide is lactose, milk sugar, which consists of one molecule of glucose and one molecule of galactose.
When we eat a disaccharide, our body needs to digest it before the simple sugars can be absorbed into the body. Digestion here means that enzymes are secreted into the small intestinal tract, and these then cut these connections so that the single sugar molecules can be absorbed.
And then we have the larger, more complex carbohydrates that contain many molecules of simple sugars. These are called polysaccharides. Poly means many. Polysaccharides are therefore large molecules consisting of many molecules of simple sugars. Starch is one example: it’s a chain of many glucose molecules. These can be simply connected in a straight chain, or in a branched-chain. Starch is very common in our diet because we find it in potatoes, starchy vegetables, and all types of grains such as wheat, rice, or corn. In starch, the glucose molecules are connected in such a way that human digestive enzymes can cut the ties. Meaning that if we eat wheat, rice, or potatoes, the starch gets broken down into single glucose molecules in our gastrointestinal tract, and then we can absorb these into the bloodstream.
Another important polysaccharide is glycogen. Glycogen is similar to some starches in that it is a highly branched chain of glucose molecules, but it is found in human or animal cells, and used to store glucose.
Another common polysaccharide is cellulose. It’s similar to starch in that it consists of chains of glucose molecules. The one important difference is that humans cannot break these chains apart, and therefore we cannot digest cellulose. For us, cellulose is therefore considered a fiber.
The last group of carbohydrates I’d like to touch on are oligosaccharides. Oligo stands for few, and this category describes carbohydrates with 3-10 simple sugar molecules. Examples of oligosaccharides include oligofructose and inulin, which you’ll find in foods such as onions, leeks, and wheat. In general, humans lack the enzymes to digest oligosaccharides, and these are therefore also considered fiber for us.
Carbs that we can digest get absorbed into the bloodstream in the form of their single sugar molecule components, the main ones being glucose, fructose, and galactose.
Interestingly, concentrations of fructose and galactose in our blood circulation are usually very low, likely because both are removed by the liver. While data for galactose suggest that some people may have relatively high plasma galactose concentrations when they consume very high doses of isolated galactose (i.e., without glucose), this does not typically occur in real life because almost all galactose is consumed in the form of lactose, i.e. galactose and glucose in a 1:1 ratio.
We’ll talk about what happens to fructose and galactose and other sugars another time. For now, what I’d like you to remember is that when we talk about blood sugar, what we really mean is blood glucose, because glucose always accounts for 90%+ of all of the sugar in our blood, even after a meal rich in fructose or galactose.
Our Blood Sugar Levels Are Tightly Regulated
The second thing I’d like you to take away from this article is that – if we are healthy – our blood sugar levels are very tightly regulated by our bodies.
Usually, in the fasting state, a normal blood glucose concentration is somewhere in the range of 80 to 100 mg/dL. Let’s just say 90 mg/dL. Now, even if we didn’t eat anything, our blood sugar would stay roughly in this range for quite a long time. And that is even though our tissues, particularly our brain, are constantly taking up a little bit of glucose from the blood and burning it as fuel. Our blood sugar levels are kept steady while we are fasting by a hormone called glucagon, which is produced by the pancreas. Glucagon stimulates the liver to release a constant trickle of glucose into the blood. That glucose comes from glycogen stored in the liver. So while we are fasting, glucagon stimulates the liver cells to break down stored glycogen, and release glucose to keep blood levels stable. If we fast for a long time, the liver can also make new glucose, mostly from amino acids, the building blocks of protein.
Let’s assume we break our fast with some bread or corn flakes or oatmeal. All of these consist mostly of starch, maybe with some added sugar. So, after digestion, mostly glucose molecules enter our bloodstream from the gastrointestinal tract, and our blood glucose level rises. In healthy people, depending on how many and what type of carbs the meal contains, blood glucose levels typically reach somewhere around 140 mg/dL at the peak in response to a mixed meal. Obviously, how much blood sugar levels rise depends on the amount and type of carbohydrates eaten, as well as a large number of other factors. This could be a very small increase, or it could be a pretty substantial increase, maybe up to 180 mg/dL or so. Before this peak is even reached though, the incoming glucose is sensed, and the pancreas stops the production of glucagon and instead now releases another hormone into the bloodstream: insulin. The figure below illustrates the potential range of typical blood glucose levels in a healthy person after a meal, and – in green – what typical insulin levels may look like.
One effect of insulin is that it tells the liver cells to stop releasing glucose into the blood. That makes sense, right? Because we now have large amounts of glucose coming into the blood from the gastrointestinal tract.
The second major effect of insulin is that it enables liver, muscle, and fat cells to take up more glucose from the blood. In these cells, insulin binds to the insulin receptor, which causes a specific glucose-transporting molecule called GLUT-4 to be transported to the cell membrane. As shown in the animation below, glucose can then enter these cells from the blood through this GLUT-4 transporter.
(Correction 12/21/2022: in the liver, it’s actually other glucose transporters, such as GLUT-2, not GLUT-4).
As a result of all of these actions of insulin, blood glucose levels start to fall, and eventually reach their steady-state level of around 90 mg/dL again. And at that point, insulin is no longer needed, and insulin levels also drop down to baseline. Depending on the size of our meal, this typically takes 1-3 hours. And only if you are metabolically healthy. If you have prediabetes or diabetes, these glucose and insulin curves look potentially quite different.
Defining Normal Glucose Tolerance, Prediabetes, and Diabetes
So what does glucose tolerance mean? And what is normal glucose tolerance compared to prediabetes and diabetes?
If we are glucose tolerant, it means that our bodies can keep our blood glucose level within the normal range, no matter how much glucose we eat in a meal.
So when I say normal range, what do I mean? Let’s see how normal glucose tolerance, prediabetes, and diabetes are defined clinically.
One way to test someone’s glucose tolerance is to conduct an oral glucose tolerance test, or OGTT. The OGTT is a clinical procedure in which a person is fasting and then drinks a beverage containing 75 g of pure glucose. That’s 15 teaspoons of sugar! The doctor draws blood before the glucose beverage is consumed, so when the person is in the fasting state, and then again exactly two hours after the person started drinking the glucose beverage.
By American Diabetes Association criteria, we would have normal glucose tolerance if our blood glucose level was lower than 100 mg/dL in the fasting state, and lower than 140 mg/dL at the two-hour time point of the OGTT.
Prediabetes is defined as a fasting blood glucose concentration between 100 mg/dL and less than 126 mg/dL, and between 140 and less than 200 mg/dL at the two-hour time point in a standardized OGTT.
Diabetes is diagnosed when fasting blood glucose is 126 mg/dL or higher, and/or if the glucose level is 200 mg/dL or higher two hours after the OGTT.
There is another test that is often used to diagnose diabetes, or to determine how well someone’s diabetes is controlled by diet or medication, and that is the HbA1c or A1c test. This test is based on the fact that glucose that floats around in our blood tends to get attached to proteins in our blood. And the higher our average blood glucose levels are, the more glucose attaches to our blood proteins. A very abundant protein in our blood is hemoglobin, the protein that transports oxygen around the body. The HbA1c test, officially also called glycated hemoglobin test, is the degree to which glucose has attached itself to hemoglobin molecules in the blood. This is expressed in percent, and less than 5.7% means normal glucose tolerance, between 5.7% and 6.4% is indicative of prediabetes, and 6.5% or higher is indicative of diabetes.
The HbA1c value gives us an idea of the average glucose concentration over the last 3 months or so. As you can imagine, over 3 months, there is a lot of up and down in our blood glucose levels, and so the average of that determines the HbA1c.
An HbA1c of 5.7%, for example, means that the average glucose concentration in blood over the past 3 months was about 117 mg/dL. An HbA1c of 6.5% indicates an average of 140 mg/dL.
So what a good clinician will do if they suspect someone may have diabetes is look at the HbA1c and also conduct an OGTT. If the test results come back totally in the diabetic range, they would diagnose this as diabetes and start treatment right away. Similarly, if all of the values are clearly in the normal, healthy range, then we can be certain that the patient doesn’t have diabetes or prediabetes. A lot of times though, these tests are not so conclusive, partly because they tend to vary a little bit from one measurement to the next. It could be, for example, that someone’s HbA1c suggests diabetes, but the fasting and 2-hour OGTT data are borderline. In those cases, the doctor would probably run these tests again a little while later.
What is amazing about blood sugar is how well this is regulated. Think about it this way. An adult man has about 6 liters of blood. That’s about one and a half gallons, a little bucket full. At a fasting glucose concentration of 90 mg/dL, a dL being 100 mL, that makes for a total of 5.4 g of sugar in all of the fasting blood. That’s about a teaspoon of sugar in a little bucket.
Now, let’s say that man undergoes an OGTT and drinks a beverage containing 15 teaspoons of glucose. How much does the blood sugar level go up? If he is healthy, maybe to 160 mg/dL. That corresponds to 9.6 g of sugar, in all of his blood. That’s two teaspoons of sugar. So all of his blood in the fasting state only has about one teaspoon of sugar in it, and even if he gulps down something that has 15 teaspoons of glucose, the amount of glucose in all of his blood never exceeds 2 teaspoons at a time. That is because the body senses glucose coming in very quickly, already when it’s in the mouth, in fact, and makes sure that it’s ready to take up glucose from the blood as all of the dietary glucose is being absorbed. It’s a pretty great example of how miraculous a healthy body is. And if you think about it this way, this process still works pretty well even in someone with diabetes.
Insulin Sensitivity and Insulin Resistance
So why is it that some people are super glucose tolerant, and others have diabetes and their blood sugar level shoots up like a rocket whenever they even have a small meal?
It’s the result of a few things going wrong in the body. Let’s start by talking about insulin resistance.
Let’s take a look at two guys: Jack and Ben. They both complete an OGTT, and – low and behold – they end up having exactly the same glucose levels during the test. As we can see in the figure below, in both men, fasting glucose is lower than 100 mg/dL, and 2-hour glucose is lower than 140 mg/dL. So they both have perfectly normal glucose tolerance.
However, if we took a look at their insulin levels during this test, we’d see some striking differences. Jack’s insulin levels start very low, rise modestly throughout the test, and then go back to baseline. That is very different from Ben’s insulin levels. These already are modestly higher at baseline, but once he drinks the glucose beverage, they take off like a rocket. These are extremes, but taken from actual people – obviously not called Jack or Ben – who participated in a clinical trial my group ran a few years ago.
What is going on here? Well, they consumed the exact same amount of glucose, and they were similarly able to keep blood sugar levels regulated within the normal range. But Ben’s body needed a lot more insulin to keep blood glucose levels in that normal range. This means that Ben is more insulin resistant than Jack. Or – if we express it the other way round – Jack is more insulin sensitive than Ben. A little bit of insulin is all it takes for Jack to regulate his blood sugar levels perfectly. Ben’s tissues, you could say, have gotten numb to insulin to some degree, and they need a lot more insulin to clear glucose from the blood.
It’s similar to, say, if your taste of salt was diminished due to some disease, and everything started to taste a bit bland, then you would need to add more salt to perceive the same level of saltiness.
Insulin sensitivity and insulin resistance are relative terms, though, and there are no clearly established clinical thresholds to diagnose “insulin resistance”, as we have for blood glucose.
So there are two things going on with Ben: one of these is clearly not a good thing because his high insulin levels show that he is very insulin resistant. The other is positive though, and that is that his body is able to make this much insulin. Insulin is produced by cells called beta-cells in the pancreas, and what we would say is that the beta-cells in his pancreas are very healthy. He has good beta-cell function, because his beta-cells are able to make more insulin if necessary. That is not the case for everyone.
If we were to visualize Jack’s and Ben’s insulin sensitivity against insulin production by their pancreatic beta-cells, they would be pretty far apart. Jack has very high insulin sensitivity, so his beta-cells do not need to produce a lot of insulin. Ben is more insulin resistant, so his beta-cells need to make a lot of insulin. And remember, in spite of these substantial differences, both men are fully glucose tolerant.
In fact, if we measured insulin sensitivity and insulin production in a large group of healthy people with normal glucose tolerance, we would get a cloud like the one on the graph below. Note how they cover the entire range of insulin sensitivity measures, from very insulin sensitive to very insulin resistant. What they all have in common is that the beta-cells in the pancreas can produce enough insulin to keep blood sugar levels in the normal range. How much insulin needs to be produced depends on how insulin sensitive their bodies are. These folks in the lower right, around where Jack is, are very insulin sensitive, so their beta-cells don’t need to make much insulin. The people in the upper left, around where Ben is, are not very insulin sensitive, so their beta-cells need to make a lot of insulin. And they are up to the task, so they have high insulin levels (hyperinsulinemia) much of the time, but their blood sugar levels remain in the normal range.
In all of these people, blood sugar levels are in the normal range, and if you only measured their blood sugar levels, you wouldn’t know that they actually differ quite a bit in how they achieve their normal blood sugar levels. Let’s just make this area green, showing that as long as someone’s insulin sensitivity and beta-cell insulin production fall into this area, they have normal blood sugar regulation.
What is very clear from this is that insulin resistance and glucose intolerance are not the same thing, and an increase in insulin resistance does not automatically lead to diabetes. Very often, when people discuss the impact of food on glucose metabolism, they say that “food x causes insulin resistance and glucose intolerance”, as if insulin resistance automatically leads to glucose intolerance. This is clearly not the case, because many people remain perfectly glucose tolerant in spite of substantial insulin resistance. The critical factor here is whether or not the pancreatic beta-cell can compensate for the degree of insulin resistance by making more insulin.
As a side note for those of you who are interested in the technicalities, the product of insulin sensitivity on the x-axis and the acute insulin response to glucose, which is a measure of beta-cell insulin production and shown here on the y-axis, is commonly called the disposition index. So Ben and Jack here, even though they differ a lot in their insulin sensitivity, may have a similar disposition index, and as a result, similar glucose tolerance.
So what if you become insulin resistant and your pancreas cannot make more insulin? Let’s take a look at another gentleman, Fred. The graph below shows changes in Fred’s insulin sensitivity and beta-cell insulin production between the ages of 25 and 55. At age 25, Fred is lean and plays a lot of sports, his insulin sensitivity is very high, and as a result, his beta-cells don’t need to produce a lot of insulin. He is glucose tolerant, meaning no matter how many carbs he eats, his blood sugar levels are always within the normal range.
Ten years later, Fred has gained 20 pounds. As we’ll discuss in detail in a separate blog post, an increase in body weight and particularly fat mass is one of the factors that can reduce insulin sensitivity. So, now with the higher body fat mass, he is less insulin sensitive, but his beta-cells were able to keep up with the higher demand. He is still fully glucose tolerant and his glucose levels are about the same as when he was 25. So there has clearly been a change in how his body handles glucose, but clinically, it isn’t apparent yet.
Another 10 years later, Fred is now 45 years old, and has gained another 20 pounds. Now, to be clear, this could continue on this imaginary line towards where Ben sits where every time Fred gets more insulin resistant, his beta-cells are able to produce more insulin. He wouldn’t even know this is happening.
Fred is not so lucky. He is again more insulin resistant than at age 35, but now his beta-cells were not able to keep up with demand. We could also say that his beta-cells are no longer able to compensate for his insulin resistance. So what we have here now is a state where his circulating insulin levels are quite high, and probably higher than when Fred was 25 or 35, but not high enough for his level of insulin resistance. His body is now no longer able to keep his blood sugar levels within the normal range, and as a result, he now has pre-diabetes. Note that his fasting blood sugar levels may still be normal, but if his doctor conducted an OGTT, or measured an HbA1c, these would likely be slightly elevated.
Another 10 years later, Fred is 55 years old, and has again gained 20 pounds. Now he has gotten even more insulin resistant. Now, not only are his pancreatic beta-cells unable to keep up with demand, they actually make less insulin than before. And now he is diagnosed with type 2 diabetes.
Now, the big question: why is the pancreas able to produce so much more insulin in Ben, but not in Fred? This topic is deserving of a separate blog post, but for now, let’s just say that whether or not your pancreatic beta-cells can increase their insulin output if they have to is to a fairly large degree related to genetic factors. That said, it is also clear that other factors that we can potentially influence also play a role here.
Let’s look at a few other examples of diabetes.
Let’s take a look at Lisa. She is 10 years old, healthy, and physically active. She develops type 1 diabetes. Type 1 diabetes is an autoimmune disease in which the body’s immune system destroys the beta-cells in the pancreas. At least acutely, this doesn’t affect her level of insulin sensitivity. However, over a few years she would lose much of her healthy beta-cells. Because she is so insulin sensitive, she again wouldn’t notice anything at first, because she may have a lot of reserve beta-cell capacity that she doesn’t need. However, once her level of insulin production drops enough, as shown in the figure, she would first develop pre-diabetes and then type 1 diabetes.
Or Monica. She is an overweight 30-year old woman. She is insulin resistant, but her beta-cells produce more insulin, and she remains glucose tolerant and healthy. But now she has become pregnant. Pregnancy, just like puberty, is a phase in which it is natural to become insulin resistant. Monica’s insulin sensitivity declines quite a bit, and her beta-cells are unable to keep up with the higher demand. She now has gestational diabetes. Once she gives birth, her insulin sensitivity may recover mostly, and the gestational diabetes may go away again. What this shows though for Monica is that her personal maximum beta-cell output is somewhere around that horizontal green line, and if she becomes insulin resistant for another reason, such as weight gain, later in life, she will likely develop type 2 diabetes.
How Insulin Sensitivity And Beta-Cell Function Are Affected By Diabetes Treatment
In general, any intervention that improves either insulin sensitivity or the amount of circulating insulin would be expected to move someone towards that normal glucose tolerance range, marked in the graphs above in green.
For example, Fred’s doctor may suggest he lose some weight. That would improve his insulin sensitivity and – depending how much fat mass he loses and how fast – it may also modestly improve his beta-cell’s ability to produce insulin. With modest weight loss, these would be expected to improve at least a little bit, and his blood sugar levels would now be better controlled.
If he had bariatric surgery and lost, say, 50 pounds or more, he would likely be able to become a lot more insulin sensitive and potentially reverse his diabetes. The same would be true if he lost this weight through other means, such as a sustained lifestyle change or medication.
Fred could also be given a drug, such as metformin, that improves insulin sensitivity.
Or, he could be given a drug in the class of sulfonylureas that improves insulin production.
Or he could be given insulin directly by injection. This would also be the treatment for Lisa, the girl with type 1 diabetes, to replace the insulin she can no longer produce herself.
Again, all of these interventions that improve either insulin sensitivity or circulating insulin levels would be expected to improve the body’s ability to regulate blood sugar levels. This will not in all cases lead to totally normal blood sugar levels, though.
Obviously, we can affect our blood sugar regulation also by what we eat, both through the immediate blood sugar effects of our foods and meals, but also through the long-term effect of our overall diet on our glucose tolerance. While that’s well beyond the scope of this article, I am planning many more blog posts on this very topic.
Glucose Effectiveness and the Role of the Brain in Blood Sugar Homeostasis
So far, we have discussed how blood sugar levels are regulated after a meal by the hormone insulin. We have seen that insulin acts directly on the liver to stop it from releasing glucose, and it also acts directly on muscle and fat cells, which causes these cells to take up glucose from the blood. We also discussed that the sensitivity of cells to insulin varies a lot from person to person and that the pancreatic beta-cells must be healthy and able to produce more insulin if cells become resistant to insulin.
But: insulin acting on cells directly is actually NOT the major mechanism by which glucose is cleared from the blood after a meal. At least not in healthy people. So let’s close with a discussion of the other part of the equation: insulin-independent blood sugar regulation.
This is rarely discussed, but it has been known for a long time that cells can take up glucose from the blood ALSO through a mechanism that does not involve insulin. A prominent example for this is glucose uptake into a muscle that is being exercised. But that is not the only example.
It is now clear that whenever our blood sugar levels rise after a meal, the elevated glucose itself contributes to greater clearance from the blood in a way that does not involve a direct effect of insulin on these cells. We know about this phenomenon mostly from mathematical modeling of the changes in blood glucose and insulin levels after a meal or during an OGTT. These models show that the clearance of glucose from the blood can only partly be explained by the actions of insulin. And using these models, it has been estimated that in healthy people, only 30-50% of glucose disposal after a meal can be attributed to the direct actions of insulin on peripheral cells.
This ability of glucose to stimulate its own disposal is called glucose effectiveness. It relates to the effectiveness of glucose itself in regulating blood sugar levels. Unfortunately, we have a lot of gaps in this area because much of the research on glucose effectiveness has been conducted in rodent models, and the relative importance and mechanisms of glucose effectiveness may differ in rodents vs. humans. To study glucose effectiveness in humans, we need fairly complicated tests that are never done in clinical settings and rarely even in clinical studies. We also need to conduct sophisticated mathematical modeling to separate the role of insulin-mediated vs. insulin-independent regulation of blood sugar levels.
So how does glucose effectiveness work? It’s clear that elevated blood glucose levels play a role, and likely a number of hormones. Now, I am calling this insulin-independent, but the truth is that insulin may actually play some role in glucose effectiveness, just not by acting directly on liver, muscle, or fat cells, but by acting on the brain. Same for glucose, elevated levels of which are likely sensed in the brain. Other hormones that may also directly signal to the brain may include FGF19 and the incretin hormones GIP and GLP-1. All of these are hormones that are regulated in some fashion by food intake, so you can think about them as additional food intake-related signals that the brain can consider when regulating blood sugar levels.
So, the scenario most consistent with the available data is that the brain senses elevated blood sugar levels, and also receives signals from all of these hormones as well, and then the brain in turn regulates the ability of the body’s cells to take up glucose from the blood. Which cells are specifically involved here is also not clear. It’s likely that insulin-independent tissues, such as the brain itself, take up more glucose if needed, but it almost certainly also affects other cells.
So overall, what you can probably appreciate is that this is quite different from what we discussed earlier: in classical insulin-dependent glucose uptake, insulin binds to the insulin receptor on a specific cell, and then that cell takes up glucose. Glucose effectiveness seems to be a process that is at least partly mediated by the brain.
We also know that glucose effectiveness is substantially reduced in people with obesity, and that reduction in glucose effectiveness is almost certainly a major contributor to type 2 diabetes.
Now, why did evolution equip us with two complementary systems to regulate blood sugar levels? One benefit of regulating something through the brain is that the brain can take in many different inputs, for example from blood glucose levels themselves as well as the concentrations of different hormones, and then fine-tune the output, which in this case is the degree to which sugar is cleared from the blood. One hypothesis is that the brain is better at finely regulating blood sugar levels than coordinating among millions of individual cells, with the end goal of keeping blood sugar levels in the normal range while minimizing the risk of hypoglycemia. Hypoglycemia means blood sugar levels that are too low (<70 mg/dL), which could be life-threatening.
To sum up the key points of what we know about glucose effectiveness:
- Blood sugar is partly taken up by cells through a mechanism that does not involve a direct effect of insulin on these cells.
- This effect is partly regulated by blood sugar levels, but likely also by a number of hormones.
- Glucose effectiveness may partly be regulated by the brain.
- Glucose effectiveness is also disturbed in type 2 diabetes, and is likely as much a cause of type 2 diabetes as insulin resistance and beta-cell dysfunction.
Summary & Conclusion
To summarize, our body goes to great lengths to make sure that our blood sugar levels always stay within a certain, fairly narrow range. When we eat glucose-containing carbohydrates such as sugar or starch, several mechanisms play together to clear the glucose from the blood and prevent the blood sugar from rising too much. While at the same time making sure that blood sugar levels don’t fall too much either. These mechanisms include insulin-dependent and insulin-independent clearance of sugar from the blood.
How well insulin-dependent clearance works is related to how sensitive tissues are to insulin, and how much insulin the pancreatic beta-cells can produce. There are numerous factors that affect insulin sensitivity as well as the ability of the pancreas to produce as much insulin as is needed. We’ll cover these in follow-up posts, and these should be pretty interesting because many of these factors are modifiable by our diet and lifestyle.
How well the body is able to clear glucose from the blood in a manner that is independent of insulin is also highly variable. One well-known insulin-independent way cells take up sugar from the blood is when a muscle is being exercised. There is also a process called glucose effectiveness that helps clear sugar from the blood after a meal in a way that does not require direct insulin binding to peripheral cells. In glucose effectiveness, elevated blood sugar levels act directly on the brain, along with a variety of hormones, to bring blood sugar levels back into the normal fasting range. Glucose effectiveness is reduced in overweight and obesity, but beyond that, not much is known about the factors determining glucose effectiveness.
So what is really going on in type 2 diabetes is that glucose effectiveness is reduced, insulin sensitivity is reduced, and the pancreatic beta-cell is unable to produce enough insulin to keep up with the increased insulin demand. Only then do we clinically develop type 2 diabetes. Any intervention that can improve either of these components, glucose effectiveness, insulin sensitivity, or beta-cell function, would be expected to improve glucose tolerance.
In type 1 diabetes, the primary defect lies in a substantially reduced ability of the pancreas to produce insulin, due to an autoimmune process that destroys the beta-cells in the pancreas. The fact that hyperglycemia and diabetes develop in this situation tells us that glucose effectiveness must also be impaired in the setting of low insulin levels (if insulin played no role in glucose effectiveness, then glucose effectiveness alone may be sufficient to maintain normal glucose levels in many patients with type 1 diabetes).
So in this blog post, we covered the basics of blood sugar regulation. I have plans for many more articles on how blood sugar regulation is affected by our body weight and fat mass, diet, sleep, stress, exercise, medication, and bariatric surgery. Diet will be a big focus, and I have plans to talk about the acute effects of different foods or dietary factors on blood sugar levels, but also the long-term effects of diet on insulin sensitivity and glucose tolerance. We will cover mechanistic links, to see what actually happens inside our body that causes defects in blood sugar regulation. I also have plans for content about the long-term health consequences of diabetes, and what is known about how we can prevent and even reverse diabetes. If you are interested in any of this, I suggest you sign up for our newsletter (sign-up form below), or subscribe to our YouTube channel. And please leave a comment below or use the contact form to let me know if there is anything in particular that you would like to see discussed. Same if anything was unclear in this post.
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