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Insulin Resistance: Are You One Of The 50% Of People Who Have It ?
Howard J. Luks, MD
Updated September 23, 2021
Nearly 50% of Americans have Insulin Resistance (IR). People with IR do not have a typical appearance. Some of you
with insulin resistance are thin and “healthy”. The presence of insulin resistance associates with many severe chronic
diseases. How do we know if you have it.. and how is IR treated?
Insulin resistance can directly cause many diseases that lead to a shorter lifespan. In addition, insulin resistance can
accelerate or worsen chronic diseases which are the most common causes of death. Insulin resistance will accelerate
atherosclerosis, thus worsen the disease course of heart disease, hypertension, dementia, and stroke.
Because insulin resistance is so prevalent, we need to have a better understanding of:
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what is insulin resistance
what drives IR
what are the downstream effects
how do we treat it?
Imagine if we could predict who might develop insulin resistance and type 2 diabetes long before your pancreas stops
working? Imagine if we could intervene long before the progression of insulin resistance to frank type 2 diabetes and
the associated chronic disease burden that comes with it? Would you modify certain food groups or change your
lifestyle to gain back years of disease-free living? I imagine that most of you will answer yes to this. The issue is that we
are often not told that something is wrong. Don’t assume that all doctors know this. Besides, we are not told what
simple strategies we could employ to help ourselves. This post is going to change that. Knowledge is empowering.
Many people will change their lifestyle if they know why they need to do it and how to accomplish it.
I have been an Orthopedic Surgeon for nearly 25 years. While I have returned many athletes to the playing field with my
knife and replaced more knee than I can count, but I am often most pleased by being able to dramatically help entire
families improve their health with lifestyle and dietary modification. Those are, by far the biggest success stories in my
practice. Returning people to a path of being metabolically healthy will impact their entire life and the lives of those
they bring along on their journey.
Contrary to popular belief among some of my peers, people will often engage if they understand why they should and
how to accomplish it. Over the last decade, I have chosen to optimize my own overall health and the overall health of
those I treat. What often becomes evident in my interactions with you is that most of you actually do want to change
your diets (within reason) and do want to exercise more. No one wants to continue their march down a path towards
heart disease, stroke, or neurocognitive decline and disability. Information is empowering. Knowing why we need to
change and how our actions can affect that change is very powerful and often very motivating.
If we could intervene early in the process of insulin resistance (less insulin function per unit amount in your blood) and
secondary hyperinsulinemia (too much insulin in your blood) then we theoretically could alter a very predictable path
towards numerous chronic diseases associated with these processes. That would allow us to intervene while your
pancreas function (insulin production) is salvageable.
In turn that might spare you a life of living with a substantial chronic disease burden.
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What are insulin resistance and hyperinsulinemia?
Why is insulin resistance harmful? Hyperinsulinemia occurs when there are excess levels of insulin circulating in your
blood. Most of your tissues require insulin to allow your cells to take glucose into them to use as a food source. The
insulin binds to an insulin receptor in the cell’s wall, and that opens a gate (Glut4 transporter) and allows the glucose into
your cell.
Yes, muscles can take some glucose in without insulin, but that occurs during exercise. If you are starting to require
more insulin in your body to accomplish the same amount of glucose uptake into your cells then you have insulin
resistance. If you have insulin resistant tissues, then your pancreas will need to make more insulin to maintain the same
glucose levels in your blood. That is what we refer to as hyperinsulinemia.
Because of the increased insulin, your blood glucose level might look normal on routine blood tests. Your A1c levels will
often be in the normal range. Your fasted insulin levels might look normal too. This is why your usual blood tests might
not reveal the presence of insulin resistance for a decade or more.
Why are insulin resistance and hyperinsulinemia bad for your health?
Identifying people with high amounts of insulin in their blood and tissues that are resistant to the effects of insulin is
very important. This should be called the pre-pre type2 diabetes stage. That means that you may not have
hyperglycemia or high glucose levels yet. It also means that your hemoglobin A1c is still in a normal range. THIS is the
stage that you want to intervene and help people become more metabolically fit. Why? Because your pancreas has beta
cells. Those beta cells make insulin. After years of churning out too much insulin, they may grow tired and worn out.
Once those beta cells stop working they may never come back (Irreversible). That is why some people with Type 2
Diabetes require insulin injections.
Hyperinsulinemia also causes your kidneys to retain sodium. That means you need to keep more fluid in your blood to
dilute the sodium. That is but one reason why you have hypertension. In addition, hyperinsulinemia is associated with
metabolic syndrome: hypertension, obesity, abnormal lipids, and glucose intolerance. Many diseases that are
commonly associated with insulin resistance, such as fatty liver disease, elevated chronic inflammation, etc also lead to
hypertension by stiffening the walls of your blood vessels. Imagine have a syringe full of water. You are asked to push
that water through a soft, thin flexible tube with the syringe. As you push the syringe, the tube expands and allows the
water to go through easily. Now, try to push that same amount of water through a stiff tube with a thicker lining. It will
be harder to do it. The pressure in the tube will be higher. This is one reason you have hypertension, and why your
heart is working harder.
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Normally, after you eat carbohydrates, your muscle tissue should store those carbs as glycogen. The two major storage
depots for glycogen are your skeletal muscle and your liver. That will happen if insulin is having its normal effect on your
muscle. In people with IR, insulin does not function normally at the level of the skeletal muscle. So the carbs you eat do
not increase muscle glycogen. The carbs instead go to the liver. The liver turns those carbs into triglycerides and
packages them into a VLDL particle. That rise in triglycerides leads to a decrease in HDL production
These are the earliest changes that insulin resistance causes. IR leads to shunting the glucose (carbs) away from muscle
storage and into your liver. Your liver turns them into triglycerides and thus causes a “dyslipidemia”- and abnormal lipid
pattern in your blood. Now… imagine, this is happening in young 20-somethings. Heart disease is an “area-under-thecurve” issue… which means that it takes place over a long period of time. So if these 20 somethings don’t alter the
course they are on, they hit their 40s and 50s with fatty liver (NAFLD), elevated lipids, heart disease, abdominal obesity,
and a markedly elevated risk of developing a heart attack, stroke, dementia, liver failure, liver cancer, breast cancer,
pancreatic cancer and more.
Triglyceride/HDL ratio
Well… guess what? We can often predict who is at high risk for hyperinsulinemia and thus Type 2 Diabetes. We can tell if
you are in the so-called pre-pre-type 2 diabetic stages. For many of you, we have the ability to recognize this process
very early on. How?
Take out your last blood tests. What were your triglycerides (Trigs) and your HDL values?
Divide your Trigs by your HDL… What is the number you get? It should be less than 3.5.
Example… My Trigs were 100, and my HDL is 65: that means that my TriG/HDL ratio is 1.5 or so.
What if your level is above 3.5? What does that mean, why is that happening and what can you do about it?
This means that a plasma triglyceride/high-density lipoprotein cholesterol concentration ratio ≥3.5 provides a simple
means of identifying insulin-resistant, dyslipidemic patients who are likely to be at increased risk of cardiovascular
disease.
This ratio works best if your BMI is + or > 25 kg/m2.
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Oral glucose tolerance tests (OGTT)
Oral glucose tolerance tests (OGTT) can help diagnose insulin resistance.
An OGTT or oral glucose tolerance test remains the current gold standard to diagnose insulin resistance or
hyperinsulinemia. During that test, we give you a drink with 75 grams of glucose. Then we check your glucose and
insulin levels at 30-minute intervals afterward. Many people who have an OGTT will be shown to have insulin
resistance. Their glucose will be elevated above what it should be, and more importantly, the amount of insulin in your
blood needed to decrease that glucose level by driving the glucose into your muscle and liver will be increased
Sugar (glucose) and its effect on your triglyceride levels
Lipids (fats) and sugar don’t mix … and this association is not logical to many of you. You’re not alone. This is not an
intuitive issue for many people. Most of you associate triglycerides with fat. That is far more logical. Most do not
understand that quite often there is a direct relationship between carbohydrate or glucose and your triglyceride levels.
Therefore, let’s review a little basic physiology and show you how sugar increases your triglyceride levels.
The liver is a highly complex organ. Glucose is necessary to maintain life. Your brain takes up 25+% of all the glucose in
your body for energy use. Your liver and pancreas work in concert to maintain your glucose level in a tight range. If the
liver has more glucose than it needs to maintain your blood glucose level then it has to do something with it. The liver
and pancreas cannot simply allow your glucose levels in your blood to rise too high. So your liver will store glucose, or
package a glucose load it sees coming from the intestines after a meal or a snack. When we eat a meal with
carbohydrates the liver can:
1. Use glucose as energy.
2. Store the glucose internally as glycogen (after exercise, or a period of fasting).
3. Convert the glucose to triglycerides, package them into a VLDL particle, and send it out in the bloodstream for
other tissues to use.
4. Convert the glucose to fat and store it internally.
VLDL stands for very-low-density lipoprotein. Your liver makes VLDL particles and releases them into your bloodstream.
The VLDL particles mainly carry triglycerides to your tissues. VLDL is similar to LDL cholesterol, but LDL particles mainly
carry cholesterol to your tissues instead of triglycerides
VLDL : Triglycerides :: LDL : Cholesterol
When the VLDL particle containing the triglycerides gets into the blood, it can release the triglycerides at various target
tissues:
1. Triglycerides can be taken up by muscle and stored as intramuscular triglyceride for energy storage.
2. Triglycerides can be taken up by muscle, broken down via a process called lipolysis, and used for current energy
needs.
3. Triglycerides can be taken up by the fat cells (adipose tissue) and stored in your adipose tissue for later use.
Intramuscular triglyceride can be used by the muscle as an energy source via a process known as fat oxidation. This will
become important later as we discuss the role of exercise and the importance of muscle mass.
As you can see, glucose (sugar) and lipid metabolism are tightly linked to one another. The hallmark of impaired glucose
metabolism is a process we call insulin resistance. This is a very complex topic that is actually very hard to precisely
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define. In essence, people with insulin resistance still retain the function of their beta cells in the pancreas. Those are
the cells that make insulin. The issue is that each unit of insulin no longer has the same magnitude of effect on many of
the tissues in your body. Thus it requires more and more insulin in your bloodstream to have the same effect as
someone with less insulin resistance. Eventually, your beta cells in your pancreas will exhaust themselves and cease
functioning. That is when people with insulin resistance and secondary type 2 diabetes require insulin injections to keep
their blood sugar under control.
At the cellular level, insulin resistance occurs because it becomes harder to transport the glucose into your muscle cells.
Your skeletal muscle really should be considered a separate organ. It is responsible, under normal circumstances, for
helping you clear the majority of glucose from your bloodstream. How does it do that?
Glucose cannot get into your cell without a transporter. In skeletal muscle, the transporter is known as the Glut4
transporter. Insulin activates the insulin receptor, then 3-4 additional steps take place which leads to the Glut4
transporter translocating across your cell wall. So the Glut4 transporters sit inside your cell until they receive a signal to
rise up and cross the cell membrane. When the Glut4 transporter is in position, glucose will move into the muscle cell
across a concentration gradient. No energy is needed for glucose to come into the cell through Glut4.
Metabolomics of Type 1 and Type 2 Diabetes
In someone with insulin resistance IR, the Glut4 mechanism is impaired. There is a break in the signal between the
insulin receptor and the translocation of the Glut4 receptor across the cell membrane. So glucose will not get into your
cells as easily.
So… if the glucose is not being taken up by the skeletal muscle, what happens to it? Remember I said that in the early
stages of IR your fasting blood glucose levels are normal. The excess glucose that is not taken up by the muscle will end
up being taken up by the liver. What does the liver do with the excess glucose? It will try to store it as glycogen, and it
packages the glucose and makes more triglycerides. This is why elevated triglycerides are a marker of poor metabolic
health. If your fasting triglyceride levels are over 100, you should consider having an OGTT.
What does it mean if my Triglyceride/HDL ratio is above 3.5?
If your number is above 3.5 then you are at high risk for developing Type 2 Diabetes and the chronic diseases associated
with it. Those diseases include heart disease, dementia, strokes, fatty liver, etc. All of these diseases reflect the
presence of a metabolic abnormality that has existed in your body for decades. Yes, these diseases can stay relatively
silent for a long time. Unfortunately, the earliest signs of atherosclerosis are now showing up in children! Imagine if we
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let that process simmer for decades before acting on it? Therefore, the sooner you start paying attention and
addressing this issue, the sooner you will be on the path towards wellness and hopefully a longer, healthier life.
What is the root cause of elevated triglycerides? The answer is often your carbohydrate intake. Our liver turns the
carbohydrates it receives from the intestines into triglycerides. Triglycerides are then transported around our body in a
VLDL. High triglyceride levels can have other deleterious effects as well. High trigs levels can cause elevated LDL small
particles which are probably more atherogenic than larger LDL particles. Elevated triglycerides can also cause a decrease
in your HDL or high-density lipoproteins. HDLs transport the cholesterol away from your tissues and take it back to the
liver. This is the process known as reverse cholesterol transport.
What to do ?
Ok… now that I have your attention. We know that carbohydrates can cause elevated trigs, and that those of us with an
elevated ratio is at risk for serious chronic diseases. What can we do to address this and minimize our risk going
forward?
You can do this…
We have two mechanisms at our disposal. First, decrease the overall calories and simple sugars we consume. Second,
we need to increase the number of calories we burn.
1. Addressing our total caloric intake
First, for most of you, all carbohydrates aren’t bad. Keto and low carb diets are all the rage now. Don’t’ get lost in the
weeds. We need to get our house in order, and that takes high-level broad changes. You can always dive deeper and
refine your new lifestyle changes at a later time. Everyone will not respond the same way to dietary changes. A diet that
works for your friends may not work for you.
Not all carbs are as “harmful” as others. Elites athletes thrive on carbohydrates. Read the work of Dr. Inigio San Milan,
an incredibly well-respected researcher, and sports physiologist. He will make it very clear that the careers of the
athletes he treats depend on very high carbohydrate diets. They do not perform well on low carb diets. Glycogen or
stored carbs are key to their power, performance, and endurance.
The main issue that drives elevated carbs being a problem, is when it is present with a total caloric excess. Taking in
more calories than we need. The carbs we need to avoid are simple, highly processed carbs such as white bread, white
rice, potatoes, sugar, pasta, bagels, cookies, etc. Complex carbs such as natural whole grains, beans, legumes, or nuts
within moderation are not going to cause a significantly elevated triglyceride level in most of us, assuming our total
caloric intake is kept under control. Taking in complex carbohydrates leads to less rapid absorption of glucose into our
bloodstream. That will make it easier for our liver and muscle to handle the glucose as it emerges from the intestines.
But again… the main issue driving insulin resistance and weight gain, is total caloric excess- eating too much, too often.
From an evolutionary perspective, this is the only time in our history on this planet when foods have been available to us
in excess and around the clock. Our bodies simply cannot process that excess number of calories properly. Insulin
resistance probably developed during the time course of evolution as a means of surviving during a period of starvation.
If an organism is starving, it would make sense to shunt the glucose away from the muscle and leave it circulating in our
blood so that it is available for our brain. We know that starvation can cause fatty liver. That is due to insulin resistance
brought on by starvation. Unfortunately, we are now seeing a fatty liver as a manifestation of insulin resistance in the
presence of caloric excesses. So our modern eating habits have caused a well-preserved mechanism to survive a famine
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and now it is working against us. Insulin resistance in the presence of excess calories will accelerate the time course of
the most common diseases that lead to our demise. Insulin resistance will accelerate the changes of atherosclerosis,
hypertension, fatty liver, NASH, dementia, etc.
2. How to increase the amount of carbs our bodies burn for energy.
We need to look at how to deal with insulin resistance in a number of ways. First and foremost is to decrease our
overall caloric intake. The second is to increase our exercise.
A. What takes glucose or sugar out of your bloodstream?
By far the biggest sink for carb storage is your muscles! Muscles store glucose for activity and to burn for current
energy needs. So it stands to reason that the larger our muscles are the more glucose they can hold and the more
glucose they will burn for energy. How do we get larger muscles? We push or pull heavy things! Even an 80-year-old will
respond and grow more muscle from one bout of resistance exercise. Resistance exercise has also been shown to
improve how your body processes and manages glucose.
Resistance training (also called strength training or weight training) is the use of resistance to muscular contraction to
build strength, anaerobic endurance and size of skeletal muscles. Resistance training is any exercise that causes the
muscles to contract against an external resistance with the expectation of increases in strength, power, hypertrophy,
and/or endurance. The external resistance can be dumbbells, exercise tubing, your own body weight, bricks, bottles of
water, or any other object that causes the muscles to contract. You can use your own body weight for resistance
exercise. Pushups, sit-ups, chin-ups, squat thrusts, lunges, and step-ups are just some of the exercises that you can do to
strengthen your body.
Best Strength Training Exercises for Diabetes
1. Squats
2. Walking Lunges
3. Pushups
4. Pullups / Lat Pulldowns
19 Bodyweight Exercises
Abdominal crunch,Reverse crunch,Superman,Push-up,Power plank,Mountain climber,Pull-up,Chair dip,Wall
sit,Wall squat thrust,One leg balance/squat/reach,Jump squat,Squat thrust,Jumping jack,Side jump,Backward
stride,Jump lunge,Walking lunge,Shadow boxing
Exercise can increase the rate at which your muscle cells take up glucose. Even in the presence of insulin resistance.
How? There is an insulin-independent process by which glucose can enter the muscle cell. This involves an important
protein complex known as AMPK. AMPK will increase in our bodies when we are exercising. AMPK will “activate” that
Glut4 transporter we spoke about earlier. IF the Glut4 transporter is working, the glucose is entering your muscle. This
will diminish the amount of glucose circulating around your bloodstream. That will leave less excess glucose available to
the liver to make triglycerides. Less glucose in your blood will decrease the signal to the pancreas beta cells to make
insulin. That decreases the insulin concentration in your blood. Insulin drives a lot of other processes too… so the lower
your insulin level, the better.
So, we know that driving glucose into our muscles can have many positive effects on our health. Therefore, it stands to
reason that the larger those muscle are, the more glucose it can dispose of and store. Therefore, it cannot be
overstated how important resistance exercise is for our overall health. I will cover this in a post at a later time, but
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having larger stronger muscles can improve our longevity and healthspan considerably. Stronger muscles take up and
burn more energy or calories. Stronger muscles help minimize our risk of falling as we age. Stronger muscles also help
us recover faster from surgery or injuries following a fall. There are only a few of you out there who can’t (because of
doctors advice) perform resistance exercises. Talk to your doctor if you are concerned about your risk. Talk to a trainer
or physical therapist if you need guidance. The muscles that matter most are your legs. So exercises like squats, getting
out of a chair without using your arms, calf raises, and so on are what you should be concentrating on. You can perform
upper body exercises too, but you should emphasize leg exercises. No doubt ageing starts from the leg.
B. Putting fewer simple carbs into our bloodstream.
So we can increase our muscle mass to take more glucose out of our bloodstream. But we also need to put fewer simple
carbs into our bloodstream. The less glucose your liver has to process, the fewer triglycerides there will be flowing
through your blood. That will decrease the number of Trigs in your body that your liver produces.
So we need to reduce simple carbs : bread, rice, cookies, and any added sugar. This can be a daunting issue for many.
Some can handle abrupt changes, many more cannot. All of you can simply pick one food group to eliminate this week
and another group next week, and so on. For example, don’t start your day with a bagel… white bread is literally the
worst offender. In addition, breakfast is not your most important meal of the day. If you are on a moderate or high
carbohydrate diet then you will crave food in the morning. That will diminish over a short period of time if you do not
feed yourself simple carbs. People on low carb diets will not have those cravings. So you can skip breakfast altogether…
or you can have a few eggs and some whole-grain toast.
By decreasing certain carbohydrate sources, we are decreasing the overall number of calories we take in. That’s what’s
most important.
C. Make your day a little harder.
A resistance exercise program and building muscle mass is a crucial step for improving our metabolism. Aerobic
exercise or increasing our net activity is also very important. Granted, most of you are not going to purchase running
shoes and bolt out the front door. What other strategies can we employ to increase your aerobic activity each and every
day? Enter the concept of making your day a little harder. Instead of circling a parking lot to find a close spot, just head
to the spot that is farthest away. These extra steps add up very quickly. Don’t print to the printer closest to you. Use a
bathroom in another part of the building you work in. Do you need to go upstairs or downstairs? Great, take the stairs.
Unless there is a medical reason not to do this then take the stairs up two flights or down three. Leave elevators for
longer excursions. Have a dog? Great. They need to exercise too :-) Take them for a long walk. Find some friends at
work who want to walk outside at lunchtime. I see this quite often, most people will not turn this request down. They
are looking for someone to motivate them too.
D. Sleep !!
Next… sleep. Yes, sleep. Sleep is so important to our overall health and well being. Below is a list of diseases that are
not caused by or worsened by a lack of proper sleep.
1. It’s true… sleep is very important for our bodies and our minds. We are a chronically underslept society. Sleep for
many is a passive process. You go to bed only after you are utterly exhausted and can’t binge-watch another episode of
your favorite shows. You need to address that by prioritizing sleep. You need to treat sleep like you treat other
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important goals. You set a time to get to sleep and you stick with it. We will all have nights when we toss and turn… but
there are many hacks available to improve our chances to get a full 8 hours sleep. Again, this will be a post that we
cover here in far more detail in the future.
Sleep improves how our body manages sugar by different mechanisms. Our brain has an influence on our liver via the
vagus nerve. The better slept and rested your brain is, the better your chances are at achieving metabolic health. The
more relaxed and well slept, the better our baseline glucose levels are. The better we sleep, the lower our internal
stress. Bottom line, sleep matters. Make it a priority in your life.