Published on November 10, 2023
Do you have hypertension, elevated cholesterol or triglyceride levels, or high blood sugar? Or maybe even all of these?
Well, you are not alone. All of these are extremely common conditions, but they are also major risk factors for several chronic diseases. It is actually also not a coincidence that these conditions often develop together around the same time, because they are all linked in one way or another to insulin resistance, or factors contributing to insulin resistance, such as visceral and ectopic fat accumulation. That’s why I call this constellation of risk factors the insulin resistance syndrome.
I am going to share how I define this insulin resistance syndrome, and why this constellation, this syndrome of associated risk factors, is probably the most important link between our diet and lifestyle and the development of chronic diseases such as type 2 diabetes, heart disease, stroke, kidney disease, liver disease, cancer, and quite possibly some neurodegenerative diseases as well.
I am going to illustrate the emergence of the insulin resistance syndrome by looking at Joe Average as he is aging from 35 to 50 and then 65 years old. We’ll be looking at his labs, and consider what is happening inside his body that so often leads to very similar changes in almost all adults as they age.
At the end of this blog post, you will be able to confidently interpret your own metabolic lab results, with the help of a downloadable sheet that I have developed. You’ll understand WHY your lab results so often get worse over time and eventually lead to full-blown hypertension, type 2 diabetes, or sky-high blood cholesterol levels. And I’ll explain how all of these are part of what I call the insulin resistance syndrome.
The Emergence of the Insulin Resistance Syndrome
So let’s take a close look at Joe as he ages to understand what may be driving the emergence of the insulin resistance syndrome.
We start with Joe in his mid-30s. He is of normal weight and plays soccer with his buddies a couple of times a week, he works out at a gym, and he generally feels very healthy. He just had his annual doctor’s visit, and the table below shows his lab results.
His body mass index, or BMI, is in the healthy category, which ranges from 20 to 25. Similarly, his waist circumference is in what I would call the optimal range. HOMA-IR, a measure of insulin resistance that we talked about before, is perfect at 1, so Joe is not insulin resistant. Or, we could also say, he is perfectly insulin-sensitive. Fasting glucose, which should be under 100 mg/dL, is also in the normal range. HbA1c, which is a measure of Joe’s average blood sugar levels over the last 3 months, is great at 4.8%. His blood pressure is a bit on the low end, which is probably perfect for his long-term cardiovascular health. Similarly, his fasting triglycerides and LDL-cholesterol levels are far below the upper limit of normal, and his HDL-cholesterol also looks good. And then we have high-sensitivity C-reactive protein, or CRP, which is a general measure of inflammation in the body. This is an interesting measure to keep an eye on, because chronic low-grade inflammation plays a key role in several chronic diseases, such as type 2 diabetes or cardiovascular disease. In 35-year-old Joe, it’s all good with a CRP level of 0.1 mg/dL.
As you can see, in red in the table above, I have not given the usual normal reference ranges, but have provided what I would consider optimal for long-term health. For example, in most lab reports, fasting triglycerides are considered normal if they are below 150 mg/dL. However, I would like to suggest that you start thinking about all of these measures more in terms of continuous variables and not just consider whether your value is above or below a certain threshold. For triglycerides, most lab reports would say that anything up to 149 mg/dL is perfectly fine, and suddenly, at 150 mg/dL, the triglycerides are flagged as too high. I suggest that in perfectly metabolically healthy people, triglycerides are usually below about 75 mg/dL, and higher levels are already indicative of a bit of a suboptimal metabolic state.
What I mean by this is not that we should freak out if a value goes up a little bit. However, what I am suggesting is that if we have fasting triglycerides of, say, 60, in our 30s, and suddenly they creep up to 80 one year, 100 a couple of years later, and then 120 another year later, maybe it would be wise to pay attention at this point and not wait until we have crossed some magical threshold. There is probably a reason for a continuous shift like this.
The same is true for LDL-cholesterol. The guidelines may say that fasting LDL-cholesterol concentrations below 130 mg/dL are normal, but the evidence does suggest that atherosclerosis develops at LDL-cholesterol levels above 70 or 80 mg/dL. Atherosclerosis is the deposition of fat and cholesterol in the artery wall that, over time, leads to a narrowing of the artery, which impairs the flow of blood and can eventually lead to a heart attack or a stroke. So that’s why I have defined an optimal LDL-cholesterol as a level below 80 mg/dL. Some cardiologists may even suggest a lower level as optimal.
All of the health markers in Joe look great, he is feeling good, and there shouldn’t be any reason for concern. However, Joe, being an average American, has always had a poor diet. More than half of his diet consists of ultra-processed foods, he eats fast food often, and enjoys sweets and baked goods, a can of soda, or a beer regularly. And by his late 30s, his career takes off and he has kids, and he feels that he no longer has time to play soccer or go to the gym.
So poor diet quality has a lot of negative effects on our health, but for now, let’s focus on one thing. If we eat a diet rich in fast food, ultra-processed foods, refined grains, and added sugars we tend to chronically eat more calories than we spend. That leads to weight gain, and the extra calories are initially deposited in the subcutaneous fat tissue. However, at some point, additional fat can no longer be stored in the subcutaneous fat depot, and instead starts to accumulate in visceral fat depots, that is, the fat depots surrounding the inner organs. And we are also seeing an increase in the amount of fat stored in tissues that are not made for fat storage, such as the liver and muscle cells. We call this type of fat storage ectopic fat. The accumulation of fat in visceral and ectopic depots is also associated with low-grade chronic inflammation in fat tissues and in the liver.
The accumulation of visceral and ectopic fat as well as low-grade chronic inflammation is what I consider the main cause of insulin resistance in most people.
One additional negative effect of a chronically poor diet is that it can make insulin resistance, low-grade inflammation, and the accumulation of fat in the liver worse. We’ll talk about this direct effect of diet in a lot of detail in future blog posts on this website, so let’s not go into further detail on this point at this time.
I also mentioned that Joe stopped working out, and so he is physically inactive, which by itself makes insulin resistance worse, and it also contributes to a loss of muscle mass, which independently induces insulin resistance.
Because he is so busy with his job, he is also chronically stressed, and struggles to go to bed on time, so he is chronically sleep-deprived. Both of these also induce insulin resistance.
Now that he has become insulin resistant, Joe’s body tries to compensate by producing more insulin, and his blood insulin levels are elevated much of the day. We call this hyperinsulinemia. And here is something interesting: chronically elevated insulin levels themselves may actually make fat accumulation in visceral depots and also low-grade inflammation worse. So in a way, a vicious cycle develops, and as long as Joe continues to overeat and continues his poor lifestyle, the situation is likely to get worse over time.
There are some other well-known risk factors that are linked quite closely to what is happening here. For one, the accumulation of fat in the liver is a problem. The liver stores fat as triglycerides, and if more than 5% of the liver tissue consists of triglycerides, then we call this fatty liver disease. Fatty liver disease is becoming a huge problem worldwide, with a global prevalence among adults of a whopping 32%. And having fatty liver disease is a risk factor for liver fibrosis, cirrhosis, and liver cancer, so that is in and of itself a risk factor for chronic disease.
Because fat is so damaging to the liver, the liver tries to get rid of the triglycerides. The problem is that triglycerides are not soluble in blood. Blood is mostly water, and fat cannot be dissolved in water. You can actually try this at home. You could take a glass of water and add some sugar or salt, stir, and the sugar or salt would fully disappear, they would be dissolved in the water. The same thing would not happen if you added some fat or oil to the water. It would just swim on top of the water, right?
So if the liver wants to get rid of the excess triglycerides, it needs to somehow package the triglycerides in a way that they can be transported in the blood. And the principal transport vehicle for fats in the blood are lipoproteins. Lipoproteins are round particles that consist of both proteins and lipids, meaning fats.
The figure above shows the general structure of a lipoprotein particle. Lipoproteins contain fats that don’t mix with water, such as triglycerides, in the center of the particle. They are the cargo. On the outside, there are molecules that play more nicely with water, such as cholesterol and certain proteins. The proteins associated with lipoprotein particles are called apolipoproteins.
The lipoprotein made by the liver is one called VLDL, or very low-density lipoprotein. This one is relatively rich in triglycerides, and the more fat is stored in the liver, the more VLDL particles the liver builds and secretes into the blood. One thing to remember here is that cholesterol is just packaging material to enable the liver to secrete triglycerides into the blood. And that means that the liver may just make a whole bunch of cholesterol from scratch so that it has enough packaging material to get rid of all of the triglycerides that have accumulated within the liver cells.
In the blood, VLDL sheds triglyerides, which are being taken up into tissues, ideally adipose tissue, for long-term storage. This is illustrated in the animated graphic above. Through that process, the amount of triglycerides in the particles decreases, and the relative amount of cholesterol and protein increases. The particle shrinks, and gradually becomes intermediate-density lipoprotein, or IDL, and eventually low-density lipoprotein, or LDL. In other words, the cholesterol that the liver originally makes as packaging material to transport triglycerides eventually ends up in LDL particles. And this is the cholesterol that we measure in the lab as LDL-cholesterol, the cholesterol bound within LDL particles.
Now, let’s be clear, there are other reasons than fatty liver that can cause elevated fasting blood concentrations of LDL-cholesterol, but because fatty liver is so common, this liver triglyceride-driven increase in LDL-cholesterol is an important one.
So what you may be able to appreciate now is that in someone with fatty liver, the liver produces more VLDL particles, and these are pretty rich in triglycerides. So if you were to measure the triglyceride content of fasting blood in someone with fatty liver disease, you would find that their fasting triglycerides are usually quite elevated. Because the liver has to make more of these VLDL particles to try to get rid of triglyerides, more LDL particles are also formed, and because LDL are pretty rich in cholesterol, such people with fatty livers also tend to have elevated concentrations of LDL-cholesterol in their blood.
And now, the last piece. There is one more lipoprotein particle that you may have heard about, and that is high-density lipoprotein, or HDL. HDL is not made from VLDL or LDL, but is built outside of the liver, and has a totally different function than VLDL and LDL particles. Now, of interest here is that HDL particles and VLDL particles interact with each other in blood. Whenever there are a lot of triglyceride-rich VLDL particles in the blood, the HDL particles take up some of those triglycerides from the VLDL particles in exchange for cholesterol (by the way, this process is facilitated by a protein called cholesterol ester transfer protein, or CETP, which for a while was of great interest because scientists thought they could affect cardiovascular disease risk by blocking the activity of this protein).
The exchange of lipids with HDL is another mechanism through which VLDL particles can get rid of triglycerides. However, in that exchange, the HDL particles lose cholesterol, in other words, the amount of cholesterol in blood that is bound to HDL particles decreases. That is why in this constellation of someone with fatty liver disease, we very often see this exact combination of elevated fasting LDL-cholesterol levels, low fasting HDL-cholesterol levels, and elevated fasting triglycerides.
In addition, insulin resistance itself, independent of whether someone has a fatty liver or not, seems to contribute to elevated LDL-cholesterol concentrations. And, insulin resistance is linked to another major risk factor for chronic disease, high blood pressure or hypertension. The mechanism of that effect seems to be at least partly that insulin affects the degree to which sodium is excreted through the kidneys, such that more sodium is retained in the body at chronically elevated insulin levels, as is typical for insulin-resistant patients.
So, to summarize, a chronically poor diet that leads to excess caloric intake, particularly when combined with a sedentary and stressful lifestyle, will lead to the accumulation of excess visceral and ectopic fat, as well as the development of insulin resistance and low-grade chronic inflammation. Over time, this constellation will also lead to a disturbance in lipid metabolism that your doctor may refer to as dyslipidemia, and that is characterized by elevated LDL-cholesterol, low HDL-cholesterol, and elevated triglycerides, as well as hypertension.
This constellation of risk factors, all of which are associated with each other, is what I call the insulin resistance syndrome. It’s similar to the metabolic syndrome, which you may have heard about. We’ll talk later about how they are similar, and why I think that the insulin resistance syndrome, as I define it, is more useful for chronic disease prevention.
The Insulin Resistance Syndrome and Chronic Disease Risks
But first, let’s talk about why this syndrome is so problematic, and discuss the relationship between the insulin resistance syndrome and chronic disease risks.
First, as I already mentioned, having excess fat in the liver is a major risk factor for liver disease, often progressing from fatty liver disease to fibrosis to cirrhosis. All of which are also major risk factors for liver cancer.
Second, insulin resistance is a major risk factor for type 2 diabetes.
Third, the accumulation of visceral and ectopic fat, insulin resistance, and type 2 diabetes are all risk factors for several types of common cancers.
Fourth, both type 2 diabetes and chronic hypertension are major risk factors for chronic kidney disease.
And lastly, let’s look at cardiovascular diseases, including heart disease, stroke, and peripheral vascular disease. We understand the risk factors for these conditions really well, and these include high LDL-cholesterol, low-grade chronic inflammation, hypertension, and smoking. And chronic kidney disease and type 2 diabetes, but even frequent blood sugar spikes as we may see in pre-diabetes, are also major risk factors for cardiovascular disease.
Treating the Consequences, Not the Root Causes
So let’s go back to Joe from earlier, and consider how, over time, the consequences of his poor diet and lifestyle manifest in the insulin resistance syndrome and major chronic disease risks.
We did look at Joe’s health parameters at age 35. Let’s now look at his health 15 years later, now aged 50. Joe is now overweight, and also still quite sedentary. He is often stressed and many nights doesn’t get more than 6 hours of sleep.
As a result, his bloodwork doesn’t look all that great anymore. If his doctor were to measure his visceral fat mass and liver fat, he would find that Joe has gained quite a bit of visceral fat, and that he now has a mild case of fatty liver disease with about 5% of fat in his liver. However, these are usually not measured, so let’s take a look at what is usually measured, or at least, could more easily be measured. As a result of his lifestyle and also the visceral and ectopic fat accumulation, his waist circumference has expanded, and he is now insulin resistant, with a HOMA-IR of 3.5 It’s not super bad yet, but still, his pancreatic beta-cells are not able to fully compensate for this degree of insulin resistance, and he has now also developed pre-diabetes. That’s reflected in his fasting glucose level of 110 mg/dL and his HbA1c of 6.0%. He now also has slightly elevated blood pressure, and his fasting triglyerides, LDL-cholesterol, and CRP are now also all quite a bit higher than they were when he was 35.
Now, none of these measures are all that bad, and if we consider the clinical guidelines, it is quite possible that none of this would as yet be treated.
So Joe continues his poor diet and sedentary, stressful lifestyle. At 65 years of age, he now is obese, and very insulin-resistant. He also has manifest type 2 diabetes, with fasting glucose at 130 mg/dL and an HbA1c level of 6.8%. His blood pressure has continued to rise, and he now clearly has hypertension. And his blood lipids and inflammation markers have gotten a lot worse as well.
Now the clinical guidelines say clearly that Joe should get antidiabetic medication, and his doctor will probably start him on some metformin. He will also receive medication to lower his blood pressure and his LDL-cholesterol levels. Now, he may not get all of this exactly at age 65. Maybe at his annual checkup at 60 he got the lipid-lowering medication, then at 62 the diabetes was diagnosed and he got the prescription for metformin, and then at 64 he needed an ACE inhibitor for his blood pressure. With all of these medications, his blood sugar, blood pressure, and LDL-cholesterol levels would come down.
If you think this is a constructed case and not very realistic, I would have to disagree. I bet every primary care physician in the United States or Europe sees a patient like this almost every day, and most people in most countries will go through this exact trajectory, or a variation thereof.
Now, what is wrong with this picture?
Two things:
First: this entire time, a time frame of 30 years, the insulin resistance syndrome built up slowly, with all of the major chronic disease risk factors gradually getting worse and worse. Yet, quite commonly, nothing is ever done to address the root causes. Not even at 65 are we usually addressing the real issue here, the poor diet and the sedentary and stressful lifestyle. And look at all of the major components of the insulin resistance syndrome that are at the heart of what is going on here: the insulin resistance, the low-grade chronic inflammation, the visceral fat and ectopic fat. In most people, these are never even measured, so we do not know about them and cannot treat them.
Of course it is a good idea to treat chronically high blood sugar, triglyceride, and LDL-cholesterol concentrations, but that alone will only lower chronic disease risk so much because there is a large underbelly of disease-causing factors that we are not addressing.
Second, we now understand very well that what matters most for chronic disease risk is the exposure to a risk factor multiplied by the time of the exposure. So, for example, if the exposure is high blood pressure, then 2 years of having high blood pressure is worse for your cardiovascular health than 1 year. Same for high blood sugar, measures of inflammation, or LDL-cholesterol.
Obviously, it’s good that we intervene and address these risk factors eventually. And let’s be clear, once someone has gotten diabetes and such elevated blood pressure and lipids, taking medications is definitely the right thing to do. However, if you were Joe, would you not have wanted to recognize, at the very least, when you were around 50 that your health was moving in the wrong direction? It’s never too late, but isn’t it obvious that in a case like this, earlier is clearly better?
What I am arguing here is that the current clinical thresholds at which we start making diagnoses (hyperlipidemia, diabetes mellitus, metabolic syndrome) is missing out on detecting the early changes that everyone who eventually develops these conditions goes through for years to decades before the official diagnosis and treatment.
I’d like to be clear that I am not trying to blame physicians here. Physicians are very much limited by the healthcare systems, insurance policies, and clinical guidelines, and let’s be honest, also by what their patients are willing to do for their own health. Also, physicians usually have their hands full caring for those who already have all of these chronic conditions. Physicians also receive very limited training in nutrition and lifestyle medicine.
No, what I am really getting at is that we all should accept more responsibility for our own health. It’s certainly easy and partly justified to blame the food industry, fast food companies, marketing campaigns for unhealthy foods, or the higher cost of healthy foods. I know it’s hard because this environment we live in oftentimes makes it difficult for us to consistently make good choices. And, of course, there are a lot of inequalities in this world and some people have bigger challenges to overcome than others for sure. But: it doesn’t help us to complain and do nothing. Our biology is what it is, and if we mistreat it for years and years, it will come with a price.
Let’s take a quick look at Joe at 65, with the lab data we just discussed, and assess his risk of developing heart disease, such as a heart attack, over the next 10 years. I entered some of these data into a cardiovascular disease risk calculator that’s run by the Mayo Clinic.
Joe’s risk of having a heart attack over the next 10 years is 39.4%. That, to me, is scary.
What if he takes the medications his doctor prescribes? If he takes the metformin, his blood sugar will be better controlled, and his blood pressure and LDL-cholesterol also come down if he takes a lipid-lowering medication and an ACE inhibitor. Still, his 10-year heart disease risk remains high at 29.7%.
Now let’s assume there was a parallel universe in which Joe had made efforts to eat well and exercise regularly since he’s been 35. The figure above shows this alternate healthy Joe and his lab values at 65. All of the values are still within the green, close to optimal area. And his 10-year heart disease risk would be estimated at 8.7%.
Now, that risk calculator is pretty good, but it does not consider several known independent risk factors, including high-sensitivity CRP and insulin resistance; if anything, this risk calculator underestimates the actual difference in risk between the unhealthy Joe and the healthy Joe. Still, these data suggest that healthy Joe’s heart disease risk is a whopping 70% lower while not taking any medications.
How to Determine if You Suffer From the Insulin Resistance Syndrome
So how can you determine if you suffer from the insulin resistance syndrome?
Let’s start with the metabolic syndrome. As I mentioned, the metabolic syndrome is a clinical diagnosis, and it is based on the five factors listed in the figure below. I have shaded that area in grey. Your doctor will make the diagnosis of metabolic syndrome if, for at least three of these five risk factors, you reach the level that is underlined.
Now, there are two things I don’t like about how the metabolic syndrome is defined.
First, I personally think it doesn’t make sense to define just one threshold. Everything under that threshold counts as OK, and then everything above that threshold counts as equally problematic. As an example, per the definition of the metabolic syndrome, fasting triglycerides of 70 are considered about the same as 145, right? Because they are both in the OK range below the threshold of 150 mg/dL. But then 155 is considered problematic, and triglycerides of 300 are considered just as problematic as 155.
I think it is much better to define rough ranges for optimal levels versus mildly elevated risk vs. massively elevated risk, which is what I have tried to do here with these colors. Which exact values we use as anchors for optimal in the green portion of each bar and as massively elevated risk in the red portion of the bar is certainly debatable, so what you see here are simply my suggestions, based on my interpretation of the literature. But, to stay with the example of fasting triglycerides, anyone could now compare where their triglyceride level falls on this scale: optimal or close to optimal in the green portion of the scale, mildly elevated somewhere in the orange portion, or massively elevated around 175-225 mg/dL or higher.
The key difference between my suggested approach and the one based on a single clinically-defined threshold is that deviations from the optimal range can be detected more easily and sooner.
The second thing I don’t like about how the metabolic syndrome is defined is that it includes fasting glucose, but not what I would consider the earlier and more fundamental change in glucose homeostasis, insulin resistance and hyperinsulinemia. Because in the early stages of people with this syndrome, whether we call it metabolic syndrome or insulin resistance syndrome, people first become insulin resistant. And they are always insulin resistant to some degree, because insulin resistance is a central part of this syndrome. Glucose intolerance may or may not develop, depending on whether an individual can compensate for their degree of insulin resistance by secreting more insulin, but I certainly feel strongly that insulin resistance is a primary defect here in this syndrome, and glucose intolerance only a secondary one that may or may not manifest.
For the same reason, I would also include high-sensitivity C-reactive protein, because low-grade inflammation is a key component of this syndrome, in my opinion. And I would also include LDL-cholesterol because it is such a key risk factor for cardiovascular disease, and so clearly linked to liver fat content and insulin resistance.
As a result of what I see as limitations in the concept of the metabolic syndrome, I have created these graphs so that you can assess to which degree your metabolic lab values deviate from the optimal state and whether you show evidence of mild, moderate or severe versions of the insulin resistance sydrome. You can download a PDF file containing these here.
A few important notes here:
The metabolic syndrome is a medically-recognized condition, i.e., your doctor could diagnose you with the metabolic syndrome. The insulin resistance syndrome, as I define it here, is not a medical condition. The purpose of the graphs is to detect early deviations from the optimal state so that the root causes can be addressed early, before medical intervention becomes necessary.
I have created versions of the poster for white men and women, and non-white men and women. That is because, depending on your race and gender, some of the data need to be interpreted slightly differently.
To clarify how to interpret these graphs:
- For most of these risk factors, except for HDL-cholesterol, higher values are usually associated with higher chronic disease risk. So, even though it’s not on the scale, fasting LDL-cholesterol of 250 mg/dL is worse than the 160 mg/dL listed on the high end here. The number I have listed in the red portion of each bar is simply the one that I think is associated with greatly increased risk.
- For fasting glucose and blood pressure, lower is clearly not better. I’d say that for blood pressure, 90/60 to 110/70 mmHg may be close to optimal, and for fasting glucose anything between 70 and maybe 90 mg/dL may be optimal.
- If you can’t get HOMA or CRP measured, this exercise still holds value even if you just have 6 or 7 data points.
Let’s use these graphs and take another look at Joe, our example from earlier. I have taken Joe’s lab values from his physical at 35, and entered them in the graph below, and we see nicely that his risk factors are all in the green.
If we now consider his data at 50 years of age, we see that they have all shifted into the orange territory. And if also did this at 40 or 45 years of age, the dots would have been somewhere in between. At 65 years old, all of his risk factors are now strongly in the red. And I hope from my explanations earlier, you now understand that it is not a coincidence that these risk factors tend to shift together. It’s not always this clear, of course, but because of how all of these are linked to insulin resistance and ectopic and visceral fat accumulation, they tend to be strongly associated with one another.
Note that there are cases where, say, LDL-cholesterol or triglycerides are elevated, even massively elevated, for other reasons. If you detect such deviations in your own lab data, it would be a good idea to discuss this with your doctor. However, for the purposes of identifying the insulin resistance syndrome as a key risk factor underlying most chronic disease, a single elevated risk factor is not what we are looking for. If excess ectopic and visceral fat and insulin resistance are the underlying factor, we usually see a shift in several or all of these eight risk factors.
I hope this also illustrates why it is better to understand what optimal looks like so that we can recognize shifts away from optimal sooner and intervene if we are so inclined.
I am hoping this poster can be practically useful for you. Once you have had your next annual physical exam and get your lab results from your doctor, ideally, these should include HOMA-IR. I explain in this blog post how this is determined. And then print out the appropriate sheet for your gender and race, and enter your data in the same fashion as illustrated for Joe above. Are you mostly in the green, give yourself a pat on the back. This is where you ideally want to be, such as Joe in the graph above at 35 or – a little less ideal but still not a big concern, even Joe at 40.
If your lab results fall mostly into the orange portion of these bars here in the middle, though, such as Joe at 45 or 50, or 55, then you are clearly on a path that could lead to full-blown insulin resistance syndrome. At this point, it’s still mild to moderate, but this is where your doctor may start to suggest a lipid-lowering or blood pressure-lowering medication. And I think the biggest benefit to graphing the data like this is that you can see where this is going, and this is therefore a great opportunity to decide whether you want to continue on this same path or make a course correction.
And if you are mostly in the red, I hope this motivates you to work with your doctor to control these risk factors, but also to do some work yourself towards addressing the root causes of the syndrome.
OK, that’s it for this blog post. As always, feel free to leave a comment below if you have any questions. And make sure to sign up for my newsletter (sign-up form is also below) if you’d like me to let you know whenever I publish new content.
Take care!
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9 Responses
Mario, good presentation overall, but you have included some parts which are wrong; it is okay, one cannot know them all perfectly.
You stated at 11:57 “The higher the LDL, the higher the risk of cardiovascular disease”. This is not true. Conventional medical advise says so, to sell statins, but this is not true. The data based on which LDL is the “bad cholesterol” is deceptively “doctored” by using relative risk and not absolute risk. LDL is not even included in the classical metabolic syndrome (“X “) definition as coined by Gerald Reaven in the 1980s.
David Diamond debunked it already. He provided plenty of evidence. This is just one of the links:
https://www.youtube.com/watch?v=XfJNUbJE_V0
I encourage you to watch David Diamond’s presentation, you will change your mind in this regard.
Also as an FYI, the healthy and young Joe Average character usually has a high (not low) cholesterol if he goes to the gym and has a good body composition (that is body fat stores below 20%, ideally below 15% in men), which makes him a “lean body hyper-responder” specifically if he is on a low carb diet. He does have all the rest in the numbers you exposed, except the lipid panel values (usually his TG are below 75, HDL is usually >60 and his LDL is usually >150, not below 80 as optimal as you presented.
But again, kudos for the effort of your presentation. Your effort is appreciated.
Hi Andrei,
Thank you for your kind feedback.
Regarding LDL-cholesterol, I am very much aware of the narrative that is out there in the low-carb community that LDL-cholesterol is not harmful, or that it is not harmful in the context of otherwise metabolically healthy people, or that it is not harmful in people on low-carb diets.
I do allow myself to have a well-educated opinion on the topic, and I dare say that I disagree with the proposed critiques. And I am not saying this lightly. I wrote my dissertation on nutrition and atherosclerosis, and I have spent around 30 years following that literature closely. I’ll make a separate video about this at some point for sure, but in the meantime, you can read my position here (review of claim #3 under https://www.redpenreviews.org/reviews/the-carnivore-code/) where my colleague Dr. Stephan Guyenet and I critiqued the book The Carnivore Code by Dr. Paul Saladino. He makes a similar argument, and I invite you to read through that, including some of the very strong evidence we cite. We actually rated his claim that “High LDL-cholesterol on a carnivore diet is not harmful” as contrary to the scientific evidence.
Now, one thing is really important to understand: if someone is overweight, has diabetes, hypertension, and elevated triglycerides, and they go on keto, lose weight and reverse their diabetes and hypertension, but their LDL-cholesterol goes up, I agree that they still may have substantially lowered their overall CVD risk. But let’s be careful here: could it still not be better to ALSO have low LDL-cholesterol? I think so. I just don’t see strong evidence at this point that the better metabolic health somehow modifies the relationship between LDL-cholesterol and CVD risk.
I do think that there is one hypothesis by Dave Feldman that very lean people on keto may develop very high LDL-cholesterol concentrations that – in this context – are not harmful. That is a hypothesis at this point, as Dave will tell you himself, and I think it’s premature and potentially harmful to already assume that elevated LDL-cholesterol in any circumstance is harmless.I personally would not gamble my health on this hypothesis being correct.
Keep up the critical thinking! Even if we end up disagreeing, I love these types of discussions, as long as they are respectful.
Best wishes,
Mario
P.S.: There are also those in the low-carb community that do value evidence. Check out Ethan Weiss, MD, for example, or Dave Feldman.
All debate/disagreements welcome as long as respectful — agreed completely. Below, there is nice article about stratification by importance of the risk factors for CV disease; LDL is almost always at the bottom.
https://www.nejm.org/doi/full/10.1056/nejmoa1800256
Thanks
P.S. Dave Feldman is one of my favorites ever, also maybe because he has no medical background, hence he is not biased by it.
Hi – am listening to you intently — white woman looking for the printouts for me — In 2024 I am spending a year to move from insulin resistant to insulin sensitive….So hurry up with the protocols already!!!!!
Very much appreciate your blogs/videos and comment/answers. Last January during my annual physical, the doc indicated I should consider statins and maybe BP meds. I noticed that my cholesterol had really not changed that much. What changed is that I got older. I guess they have to cut off somewhere but apparently being 70 is worse than being 68 as far as greater chances of bad outcomes from non-optimal cholesterol levels. LDL 121, Trig 60, HDL 87. While LDL is too high, I have read some theories that Trig to HDL may be more important indicators. My blood pressure was also high but after measuring at home, I believe this was just the stress of being at the doctor’s office. I actually played around with one of the 10 year risk calculators, and even if I lowered my LDL, it didn’t seem to matter much. Lowering my blood pressure though made a lot of difference as far as much less risk in the calculation. I also noticed my fasting glucose was 111, something the doc didn’t even mention. That is what got me interested in glucose management so I tried a CGM. My BG definitely shoots up when I eat much in the way of carbs and I had already tried some of your techniques to temper those spikes. In the past year, I have embarked on a serious effort to improve my heath via food choices and understanding nutrition better. I already exercised some and now am doing more. I’m not exactly sure how I found your website but I’m very glad I did. I do see some people seem to want to have a complete flat line with the blood glucose, avoid all carbs, freak out at a 30 point spike etc. I have thought – but what about the nutrients. Sure fruit has sugar, but it has lots of vitamins too. Your advice saying the same thing is a relief! I’m going to go back and read/watch everything so far and patiently await further missives from you. Thanks so much!
An excellent & informative discussion/lecture.
Hopefully it finds it way to MD’s.
I have forwarded it to fellow colleges (retired dentists ) + interested friends.
Thank you.
Terry Honeysett
Been trying to puzzle through how to apply this kind of data to my own life. My cholesterol has been at the very high end of normal since I was 20. I’m not overweight or carrying a lot of visceral fat, my blood sugar is good, and my blood pressure is quite low. But my LDL is around 120 and my HDL is just under 50. It hasn’t gotten worse in almost 20 years but it hasn’t gotten better either. Been vegetarian and active the whole time. It’s so hard to tell from the literature whether I’m somebody with naturally higher cholesterol and it doesn’t matter since my other indicators are good, or it’s an early warning I should address now. Sigh.
Thank you for sharing.
In the blog post and video, I share how elevated LDL-cholesterol is often the result of other, commonly hidden changes in the body, and associated with elevated triglycerides, insulin resistance, low-grade inflammation, and elevated levels of ectopic and visceral fat. That’s the constellation I call insulin resistance syndrome.
From your explanation, it sounds as if it’s unlikely that a hidden insulin resistance syndrome is the cause, or a contributor, to your slightly elevated LDL-cholesterol. Having additional data on TG and HOMA-IR would help ascertain that this assumption is correct.
If TGs and HOMA-IR are also low (in the green area on the downloadable sheet), then it’s likely that your LDL-cholesterol is slightly elevated for another reason. Not that 120 mg/dL is particularly high, or high-risk in the absence of other risk factors, but if you’ve had LDL-chol of 120 mg/dL since your 20s, that would suggest that you may have one or several minor genetic variants that predispose you to some slightly higher LDL-chol. There are hundreds of genetic variants, some of which have a huge impact, with LDL-chol in the 300s or 400s, but there are also many more that slightly increase levels within or to just above the normal range.
The very next video will tackle LDL-chol, apo B, and other lipid-related CVD risk factors, because so many people had questions about that, so I am hoping this will provide some insights for you.
Cheers
Mario
Thanks so much for replying. I do suspect genetics. I had a stomach problem in my early 20s that made me lose 30 lbs (which I gained back when I got healthier) and even that didn’t lower my blood lipids. My triglycerides are fine if not stellar – around 100. I’ve never had fasting insulin measured but I spent a couple weeks with a CGM testing things out and everything looked really good – low coefficient of variation, something like 97% of time under 120 even though I don’t eat low-carb. I also have an abdominal CT and it clearly shows no fatty liver. I know I don’t have the most common FH variants, and I’ve looked through the literature looking for less common ones (nerd that I am), but amidst GWAS studies I haven’t found anything particularly enlightening for me personally. My mother is almost 70 and has the same situation: not overweight, not diabetic, very low blood pressure, triglycerides at 100, and similar LDL and TC values (and actually her TC is over 200 now). She’s active and has no heart issues and great kidney/liver function. It’s hard to know if this means I should completely ignore my cholesterol, or if I should be extra careful about saturated fat, or what, in trying to protect my health in the long term.