Dr Ritamarie
Imagine two people sitting in your office. They both have a fasting blood sugar of 88. They both have an A1C of 5.2, and based on those numbers, you’d probably tell both people that their sugar looks good. What if one person’s pancreas is releasing substantially more insulin than the other just to keep those numbers looking normal? What if one person’s metabolism is functionally efficient while the other’s is compensating for insulin resistance?
Same glucose, same A1C, but very different metabolic situations. Here’s the problem. If you’re only looking at glucose and A1C, we may not recognize that the difference is there until much later when the compensation starts to fail. The real question isn’t just how much glucose is circulating in the blood, it’s what the body has to do to keep it there.
Today, we’re going to explore what insulin might be telling us that glucose alone can’t, why metabolic dysfunction can develop before blood sugar becomes abnormal, and how to recognize the patterns that deserve a closer look.
When it comes to metabolic health, waiting for blood sugar to rise may mean that we’re missing an important opportunity for early intervention.
One of the things I’ve been teaching practitioners for decades is that we need to move beyond looking at isolated numbers. We need to understand what those numbers represent, how different systems are communicating, and what the body may be doing to compensate for things that are out of balance.
Insulin is an absolutely perfect example. We’re accustomed to thinking about insulin in relation to diabetes, and it’s easy to overlook the many other things that this hormone does.
It’s easy to overlook the possibility that a person can have normal glucose while their insulin regulation is already changing, and that can be causing a diverse amount of other symptoms in the body. I want you to be really clear about one thing from the beginning. I’m not suggesting that normal blood sugar is a bad thing. Of course, we want healthy blood sugar regulation, but I do want to challenge the assumption that normal glucose automatically means everything is working optimally metabolically, because a normal result doesn’t necessarily tell us how much effort the body’s putting in to maintain that quote unquote normal level.
That’s what we’re going to unpack today. Insulin is a hormone that’s easy and inexpensive to test, yet, very few practitioners order it. It gives us clues about metabolic dysfunction long before glucose and A1C do.
When most people think about insulin, they think about blood sugar, of course. And, of course, most patients don’t know the difference. I’m always having to explain it to them. We know that insulin helps regulate glucose and that insulin dysfunction plays a critical role in type 2 diabetes, but insulin is involved in so much more than just glucose and moving it out of the bloodstream and into the cells.
In fact, when we start looking at its many actions throughout the body, we can begin to understand why insulin resistance and hyperinsulinemia are associated with so many different health problems. Let’s look at some of the major functions.
First, of course, insulin helps glucose. It gets uptaken into the cells, particularly skeletal muscle and adipose tissue. When insulin binds to its receptor, it activates a cascade of intracellular signals.
One of the outcomes is that GLUT4 transporters move from the cell membrane into the cells and allow the glucose to get in, and skeletal muscle is especially important here. Muscle is a major site of insulin-stimulated glucose disposal, and that means muscle mass, especially muscle quality and muscle insulin sensitivity, may play important roles in glucose regulation. That’s one reason I emphasize building and preserving muscle as part of metabolic health.
Secondly, insulin helps regulate glucose production by the liver. When we’re not eating, the body still needs glucose. The liver helps maintain blood glucose through glycogen breakdown and gluconeogenesis, and insulin normally helps suppress excessive glucose production by the liver. When the liver becomes resistant to insulin signals, the suppression may become less effective.
The liver can continue releasing more glucose than the body needs, and when that eventually contributes to elevated glucose, we’re all blaming the diet. It’s not necessarily the diet.
Here’s what’s interesting. The liver’s response to insulin isn’t necessarily an all-or-nothing response. Some insulin-regulated pathways may become resistant, while others remain more responsive, and we’ll talk more about that in a moment.
Insulin and fat metabolism is another way of looking at what insulin does. It plays a major role in fat metabolism. That’s one of the areas where I think insulin is frequently misunderstood. We often refer to insulin as a fat storage hormone. The reason that it’s a fat storage hormone, or considered that, is one of insulin’s most important functions is to actually inhibit lipolysis, the breakdown of fat.
It’s a breakdown of stored triglycerides specifically into fatty acids and glycerol. Normally, when we’re fasting or when the body needs to mobilize stored energy, the glycogenolysis, lipolysis, is increased. The stored triglycerides are broken down and fatty acids are released into circulation, so they can be used as fuel. After we eat, insulin sends a signal to adipose tissue that essentially says, “Hey, nutrients are coming in, so we don’t need to mobilize as much stored fat right now.” At the molecular level, insulin binds to its receptor and activates the IRS, PI3K, and AI.KT signaling pathways.
One of the downstream effects involves the activation of phosphodiesterase 3B, which helps to reduce cyclic AMP, and when cyclic AMP decreases, protein kinase A activity decreases, which means there’s less activation of the machinery involved in breaking down stored triglycerides, including hormone-sensitive lipase and the proteins that regulate access to stored fat, so insulin suppresses lipolysis
At the same time, under appropriate conditions, insulin supports glucose uptake and triglyceride storage in adipose tissue. That’s the part of how the body coordinates energy storage after a meal. That’s the normal physiology. We don’t want to eliminate that process.
Here’s where it gets really, really interesting. What happens when adipose tissue becomes insulin resistant? Well, one possibility is that insulin becomes less effective at suppressing lipolysis, and even though insulin levels may be elevated, the fat cells don’t respond as effectively to that antiolytic signal. Instead of appropriately suppressing fatty acid release, adipose tissue may continue to release excessive amounts of fatty acids into the bloodstream, but we don’t need them now, because there’s food in there, and they can reach the liver and skeletal muscle.
When the delivery exceeds what the tissues need, like right after meals, it can contribute to ectopic fat accumulation, metabolic stress, and further disturbances in insulin signaling.
Think about the apparent paradox here. Someone can have high insulin and still have excessive fatty acid release, because their adipose tissue isn’t responding normally to insulin. That’s a very different picture from simply saying that insulin causes fat storage.
It depends on which tissue we’re talking about and whether that tissue is responding appropriately to insulin or whether it’s resistant. I think that’s really important to consider here. Practitioners need to understand this as we guide our clients and patients.
Dr Ritamarie (08:55)
Another important function of insulin is anabolic effects. It influences protein metabolism and helps regulate the balance between protein synthesis and protein breakdown.
Insulin helps suppress muscle protein breakdown, and it works alongside amino acid availability and other signals involved in maintaining muscle tissue. Insulin isn’t just about glucose or fat, it’s also involved in amino acids and the use of proteins throughout the body.
Fifth, insulin participates in a broader cellular signaling pathway system. Some of those pathways involve cell growth, nutrient sensing, and metabolic adaptation. What this means is that changes in insulin signaling may have implications way beyond blood sugar regulation. It helps to explain why insulin resistance is associated with disturbances involving the liver, cardiovascular systems, reproductive hormones, and other physiologic systems, which we’ll explore in detail in later episodes.
For now, I want you to remember something. Insulin isn’t the villain, as we sometimes call it in insulin resistance. Dysfunctional insulin signaling is the concern. Well, you need insulin, obviously. Type 1 diabetics don’t have it, and they have a hard time surviving without being given it. The goal isn’t to eliminate insulin or suppress all the normal rises in insulin after eating. The goal is that we have appropriate insulin secretion and appropriate insulin clearance and healthy responsiveness in the tissues receiving its signals.
When we begin to think about insulin this way, we can see why normal glucose doesn’t necessarily tell us everything about how those signals are working.
Let’s get back to those two people we talked about at the beginning. Same fasting glucose, same A1C.
How could their metabolic situations be so different? One possible explanation is metabolic compensation, and this is something I really want all of us as practitioners to understand.
The body has an intricate system and an ability to compensate when things aren’t working as efficiently as they could. As I like to say, the body compensates until it can’t. Sometimes those compensations are so effective that standard lab markers look normal, at least for a while, and let’s just say somebody’s skeletal muscle becomes less responsive to insulin.
Normally, a certain amount of insulin is sufficient to stimulate glucose uptake into those muscle cells. As insulin sensitivity decreases, that same amount of insulin produces a smaller response, and the body needs to compensate. How does it do that? By secreting more insulin, and it stimulates the pancreatic beta cells to go boom, boom, boom, make more. Now there’s more insulin circulating, and that increased insulin may help overcome some of the reduced responsiveness. As a result, the blood glucose can stay normal until it can’t.
If we’re only looking at fasting glucose or A1C, not postprandial, we may not realize how much compensation is taking place. If we’re not looking at insulin levels, which most doctors don’t, we’re not going to see that.
Here’s a critical point. Glucose can be normal, because the body’s successfully compensating for it by making more insulin. but that compensation can actually continue for quite some time, as much as two or three decades.
In some people, it can go longer, and eventually, if insulin resistance progresses and beta cells can no longer maintain adequate compensation, the blood sugar may start to rise. But, the timing varies. Not everybody progresses in the same way.
In fact, elevated insulin and insulin resistance can have complex sometimes bidirectional relationships. Reduced insulin sensitivity can lead to increased insulin secretion, but sustained elevations in insulin can also influence insulin responsiveness. The cells become resistant. We’re not necessarily looking at a simple one-way process. The important thing is that insulin regulation can change, before glucose becomes abnormal, which makes me recommend that everybody get at least a fasting insulin, if not also a postprandial. We have opportunities to recognize metabolic dysfunction really much earlier if we’re looking at insulin.
Let’s look at this. Let’s look at an analogy that I think makes it easier to understand. Can you imagine two cars traveling 60 miles an hour? One is cruising effortlessly along the road, another is climbing a steep hill. The engine is working much harder in the car going uphill. They’re both traveling at exactly the same speed, but one has to work harder to get there. The amount of work required is similar to what’s happening with insulin. It’s very different, but same speed, same external appearance. It’s one way to think about the two people in the same place. One person’s body is maintaining the glucose with relatively little insulin. The other person may need substantially more insulin to accomplish the same thing.
We don’t know unless we test the insulin. If we’re only measuring the glucose, we don’t see that. We don’t see how much effort is being expended. I’m a big fan of testing insulins and testing C peptide, and seeing what the body’s actually doing. Our metabolism is a lot more complicated than a car engine, and we’ve got all these organs and hormones and feedback loops and signaling pathways interacting with each other.
The analogy illustrates something important. Normal outcome doesn’t necessarily mean the process that’s producing the outcome is functioning optimally, and that’s what we’re looking for. We want to help people to function optimally.
This can be applied to so many areas of health. We look at thyroid function, adrenal signaling, reproductive hormones, metabolic regulation. We need to understand that it’s not just the final numbers, but also the compensatory mechanisms that may be involved, and insulin is a beautiful example of this.
Dr Ritamarie (15:17)
Let’s talk about two distinct insulin dysregulation situations. We talk about hyperinsulinemia, too much insulin or a lot of insulin, and insulin resistance. While hyperinsulin anemia often accompanies insulin resistance or precedes insulin resistance, elevated insulin alone doesn’t establish that someone is insulin resistant. And, the reversal is also important to look at.
A normal or relatively low insulin concentration doesn’t necessarily rule out metabolic dysfunction. For example, someone with more advanced metabolic disease may no longer be able to make or maintain the increased insulin secretion, because the pancreatic beta cell function has declined. That’s why I recommend doing fasting insulin and also postprandial.
We can’t assume that everybody with insulin resistance has elevated insulin, although most of them precede. We can assume that they have an issue with the underlying physiology.
High insulin doesn’t tell us everything, and normal insulin doesn’t automatically tell us everything’s working.
That’s why I encourage practitioners to move beyond isolated markers and understand the physiology and the biochemistry behind the result. This is so critical for us to understand.
Another concept that makes this even more interesting is that insulin resistance isn’t necessarily uniform throughout the body. It’s not one condition. The muscle cells, the fat cells, the liver cells, all different systems may have different levels of insulin resistance. It can vary across the tissues and even within the same tissue, different signaling pathways may respond differently.
I’m going to give you an example of that. In the liver, insulin normally helps suppress glucose production, because we don’t need it. We have plenty of glucose in the blood. But, insulin also participates in pathways involved in lipid synthesis, and in certain insulin-resistant states, insulin’s ability to suppress the hepatic glucose production becomes impaired while the lipogenic signaling can remain relatively active.
This phenomenon is sometimes referred to as selective insulin resistance and explains how someone can have impaired glucose regulation alongside increased liver fat production. Now the actual physiology is complex and several nutrients and hormonal signals contribute to lipid accumulation, fatty liver in the system, but the larger point is this, insulin resistance doesn’t necessarily mean every insulin-regulated pathway stops responding.
Some signals may become less effective, others may remain active, and that helps explain why we can see so many different appearances of metabolic dysfunction and sometimes contradictory findings in the same person.
Think back to the adipose example. Insulin can be elevated, but its ability to suppress lipolysis may be impaired. Meanwhile, other insulin-related metabolic pathways may still be functioning. It’s really important that we understand the physiology and that we look deeply at each person.
What I believe is that practitioners need to understand signaling pathways rather than just treating insulin resistance as a uniform problem. We need to understand biochemical pathways. We need to understand the physiology and the way things are signaling. When we can do this, we can recognize patterns that we may otherwise miss.
Why am I spending so much time explaining this physiology? Well, it’s fascinating to me, first of all, but it changes the questions we ask.
If we think insulin is simply a hormone that lowers blood sugar, then we may focus almost entirely on whether glucose is elevated, and that’s what standard conventional medicine does.
Once glucose becomes abnormal, we start looking for ways to bring it back into range, but by then, it’s been going on for so long that it’s harder and harder to do.
If we understand this insulin as a signaling hormone, fat metabolism hormone, protein metabolism, a multiple tissue pathway, we start to ask different questions, and the power of questions is so valuable to us as healthcare providers helping people.
Is this person insulin sensitive? Are they responding appropriately? Is the pancreas having to compensate by releasing more insulin? Then, is it getting tired, and is it going to collapse? Then, we see changes.
Insulin clearance is super, super important to look at as well. If we’re seeing signs of metabolic dysfunction in other symptoms, even though glucose remains normal, we need to be looking deeply. These questions take us beyond simply asking whether somebody has diabetes or pre-insulin resistance or insulin resistance. We’re trying to understand the underlying physiology, and that can make an enormous difference in how we approach prevention and personalized care.
I don’t want this to be interpreted as meaning that every normal glucose result is suspicious. No, a lot of them are good, but not that many people are metabolically well. We shouldn’t assume that metabolic dysfunction is present whenever somebody has a symptom we can’t explain. I’m not saying that either. What I’m saying is that a reassuring glucose result shouldn’t automatically end the investigation and have you start to look for something else when the rest of this clinical picture suggests that there may be a metabolic imbalance happening. We need to look for the meaningful patterns.
We need to understand the mechanism that can connect the patterns, and that’s what I mean when I talk about becoming a better clinical detective and looking beyond protocols. So many times we memorize protocols and these herbs and this nutrient and this drug for this condition.
If you’re a practitioner who really wants to get better at recognizing patterns, I created a resource for you called Beyond Protocols, A Practitioner’s Guide to Root Cause Pattern Recognition.
If you want to get access to that, go check the show notes and download it, because knowing what lab markers to order is only part of the process. The real skill is learning how to connect the dots and understand the underlying physiology and biochemistry and recognize what findings need priority first. If you’d like that guide, just check out the show notes. There’s one more important idea I want to leave you with.
Dr Ritamarie (21:40)
One of the most important principles in physiology is that the body is constantly adapting. It’s adjusting hormone secretion. It’s changing the receptor responsiveness. It’s modifying metabolic pathways, and it’s coordinating signals among different tissues to help maintain internal balance.
That’s what homeostasis is all about, but sometimes maintaining a normal result requires more effort than it should. The fact that the body is maintaining that result doesn’t mean that there isn’t an underlying problem developing.
Think about someone whose blood pressure is being maintained through changes in vascular tone and hormonal signaling, or someone whose thyroid hormone levels remain within normal range while compensatory signaling changes. Those systems are more complex than any laboratory value, and there’s so many different things going on that we need to look at them in detail.
Insulin regulation is no different. A person can have normal blood glucose for a long time, even as the insulin sensitivity changes. I encourage you to look at insulin levels, as well. For a period of time the pancreas can compensate until it can’t, and if we only look at elevated glucose, we’re going to miss the compensation.
Now, as an important caveat, compensation isn’t automatically harmful. It’s normal, and it is a central part of human physiology. The concern is whether the the compensatory response is sustainable and whether it’s occurring alongside other signs of dysfunction. If it’s not sustainable, the body’s going to break down. That’s why context matters so much, and it’s why the goal of root cause evaluation isn’t to find abnormality in every normal test. It’s to understand that the normal test result may not mean that there’s no underlying dysfunction.
Sometimes the earliest clues aren’t telling us that the system failed. It’s telling us that the system has to work harder to maintain normal function. I think it’s an incredibly important shift in how we look at metabolic imbalance and metabolic health.
Let’s bring this all together. It should be clear now that insulin is much more than a blood sugar hormone. It participates in glucose regulation, in fat metabolism, in protein metabolism, in nutrient signaling, and other physiologic processes.
When insulin regulation becomes dysfunctional, we shouldn’t expect the effects to be limited to glucose, and normal glucose doesn’t necessarily mean normal insulin regulation. Again, I’m going to encourage you to test insulin, fasting and postprandial. The body can compensate for reduced insulin sensitivity by increasing insulin secretion, and there’s all kinds of side effects of that, which we’re going to talk about in a couple of other episodes coming up.
We can’t assume that normal glucose or A1C tells everything about metabolic health. Please get that into your head. It’s so important and so many people are being told that. Just remember, don’t just ask whether blood sugar is normal. Ask what does the body have to do to keep it normal? Because, sometimes the most important clues come from understanding the compensatory mechanisms that are keeping a lab results than range. That’s what helps us from simply managing numbers to understanding the physiology behind them, and that’s so critical, and it’s missing in medicine.
We spent a lot of today understanding the physiology of insulin and blood sugar regulation, but how do we recognize these patterns in actual practice? How do we know when normal glucose is truly reassuring and when we might need to look more deeply? What can fasting insulin tell us? What about HOMA IR? What about oral glucose tolerance testing or doing that at home? Continuous glucose monitoring. All of these things are important.
This is how we can interpret results without relying on arbitrary cutoffs or treating any one test as the final answer. It’s exactly what we’re going to explore in our next episode. We’ll take this physiology and turn it into practical clinical detective work, looking at the clues that may help us recognize metabolic dysfunction even when glucose and A1C look perfectly normal. I hope you come and join me for that.
This is what reinventing healthcare is all about. We’re moving beyond isolated symptoms, isolated lab values, and recognizing the patterns that connect them, and understanding the underlying physiology and compensations, so we can create more personalized root cause approaches.
I believe that the future of healthcare depends on practitioners who can think this way. Practitioners who ask better questions, understand how the body communicates, and look for the underlying causes of dysfunction rather than simply waiting for disease to become obvious, which is a Western medical approach. That’s why I’m so passionate about teaching nutritional endocrinology and helping practitioners develop those skills.
If you’re a health practitioner and you’d like to go deeper, I invite you to download my free Beyond Protocols guide. The link is in the show notes. Check out our website for other courses and programs and free guides, and I’ll help you start thinking beyond isolated findings and one size fits all protocols. You’ll find all the links you need in the show notes.
If today’s episode helped you see insulin and metabolic health through a different lens, please follow ReInvent Healthcare and share this with other practitioners that you know, because it can make a huge difference in the kind of care that people are getting. Thank you for joining me on my quest to reinvent healthcare. And until next time, shine on.
What’s Inside This Episode? Why a diagnosis of osteoporosis doesn’t explain why bone is being…
What’s Inside This Episode? Why having more tools does not always lead to better outcomes…
What’s Inside This Episode? Why the T-score is important but never the complete bone health…
What’s Inside This Episode? Why your client’s sleep problem may not actually be a sleep…
What’s Inside This Episode? Why bone is a living collagen matrix, not simply a place…
What’s Inside This Episode? Why a DEXA scan may not tell you the full story…
This website uses cookies.