Insulin Resistance & Elevated Glucose
Nutritional and Lifestyle Interventions for Mitigating Chronic Disease.
Nearly 50% of Americans have Insulin Resistance (IR), leading into pre-diabetes and Type II diabetes. People with IR do not have a typical appearance. Some people with insulin resistance are thin and “healthy”. The presence of insulin resistance is associated 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 worsening the disease course of heart disease, hypertension, dementia, and stroke. Because insulin resistance is so prevalent, we need to have a better understanding of:
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 II Diabetes long before your primary care physician identifies your glucose levels have become dysregulated during your annual check-up. Imagine if we could intervene long before the progression of insulin resistance to Type II 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 would assume most of you will answer yes to this. The issue is not that we aren’t being told that something is wrong (as many articles might say otherwise). Insulin resistance actually develops in the skeletal muscle, long before your actual blood sugar even becomes out of range.
Knowledge is empowering. Many people will change their lifestyle if they know why they need to do it and how to accomplish it.
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. In turn that might spare you a life of living with a substantial chronic disease burden.
What is insulin resistance and hyperinsulinemia?
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 source of growth. The insulin binds to an insulin receptor in the cell’s wall, and that opens a gate, allowing 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 really be referred to as pre-pre diabetes. 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 where you want to intervene and help yourself 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. That is why some people with Type II 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 hypertension is so prevalent in those with diabetes. 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 having 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. A simplified example but one that explains the presence of hypertension.
Normally, after you eat carbohydrates, your muscle tissue should store those carbohydrates as glycogen. The two major storage depots for glycogen are your skeletal muscle and your liver. These stores will be filled when insulin is having its normal effect on these organs. In people with IR, insulin does not function normally at the level of the skeletal muscle. So the carbohydrates you eat do not increase muscle glycogen. The carbohydrates instead go to the liver. The liver turns those carbohydrates into triglycerides and packages them into a VLDL particle. That rise in triglycerides leads to a decrease in HDL production, also deemed as dyslipidemia.
Now… imagine, this is happening in young 20-30 year olds.
Heart disease is an “area-under-the-curve” issue… which means that it takes place over a long period of time. So if these young individuals don’t alter the course they are on, they hit their 40s and 50s with fatty liver, termed (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.
Oral glucose tolerance tests (OGTT) can help diagnose insulin resistance.
An oral glucose tolerance test OGTT remains the current gold standard to diagnose insulin resistance or hyperinsulinemia (outside of clinical research settings). During that test, you’re given a drink with 75 grams of glucose. Baseline levels of your glucose and insulin levels are assessed through lab draw, and again at 30-minute or 1-hour intervals afterward. Many people who have an OGTT will be shown to have at least slight 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.
Researchers at Yale have found evidence of insulin resistance in 30-40% of thin, healthy appearing college student volunteers when subjected to an OGTT. Why would this be the case? These people were young and “healthy”. These individuals were also… sedentary.
Sugar (glucose) and its effect on your triglyceride levels
Lipids (fats) and sugar don’t mix. They're two separate types of macronutrients, and the body responds and metabolizes them in completely different ways. Most people might associate triglycerides with fat in having the same metabolic effects. I know I certainly did as I began my education career in nutrition. Most do not understand that quite often there is a direct relationship between carbohydrates or glucose intake and your triglyceride levels. Therefore, let’s review some 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% or more 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 normal blood sugar 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 has some different options. It can:
Use glucose as energy.
Store the glucose internally as glycogen (refueling after exercise, or used as energy during periods of fasting).
Convert the glucose to triglycerides, package them into a VLDL particle, and send it out in the bloodstream for other tissues to use.
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. When the VLDL particle containing the triglycerides gets into the blood, it can release the triglycerides at various target tissues. They can be:
taken up by muscle and stored as intramuscular triglyceride for energy storage.
taken up by muscle, broken down via a process called lipolysis, and used for current energy needs.
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 and lipid metabolism are tightly linked to one another. The hallmark of impaired glucose metabolism, as we’ve discussed, is insulin resistance. 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 after 3-4 additional steps take place which leads to the Glut4 transporter translocating (moving across) 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.
In someone with insulin resistance, 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 because glucose now struggles to get into your cells as easily, it will progress into your body needing more and more insulin to push it through.
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 insulin resistance, 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. Most primary care clinics, doctors and recent publications regarding normal biomarkers have now moved the “normal” levels of triglycerides <150 (mmol/L), with preference of being closer to around 100 or less.
1. Addressing Total Caloric Intake
To begin this section regarding nutrition, I’d like to make a highly provocative statement that carbohydrates aren’t bad. I feel like the hype around Ketogenic and low carbohydrate diets are subsiding to some extent, though still without a doubt have their place in medical nutrition therapy. Have you experimented with a certain dietary change and found it didn’t work in the least bit or even found yourself going the other direction you intended? Don’t be upset or get down on yourself when certain dietary or lifestyle changes don’t seem to work as well as a friend of yours. Everyone will not respond the same way.
Carbohydrates take different forms, affecting some more than others. It’s well known that many elite athletes thrive on carbohydrates. A recent paper regarding fueling for athletic performance states that glycogen or stored carbohydrates are key to their power, performance, and endurance.
The main issue that drives elevated carbohydrates being a problem, is when it is present TOGETHER with a total caloric excess. Taking in more calories than we need. The carbohydrates you might want to steer clear of if not participating in high level athletics are going to be those, refined and highly processed. It’s become abundantly clear through the literature these foods simply spike our hunger hormones, driving us to continue to eat, even past the point of being satiated. 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 is hypothesized as probably developing 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, and excessive fasting periods can induce 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 and now it is working against us.
2. How to increase the amount of carbohydrates our bodies burn for energy.
How can we mitigate insulin resistance?
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 carbohydrate 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 increase muscle size? We lift. I tell my clients that lifting weights is the best possible exercise to engage in, not only for the issue of insulin resistance, but solely from a strength building perspective. As we age, your strength is incredibly important. As said previously, your muscle site is a large storage pool for fatty acids and triglycerides. When engaged in activity like walking, cycling or resistance training, it’s glucose in addition to fatty acids that are being utilized as well.
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 muscles are, the more glucose it can dispose of and store. Therefore, it cannot be overstated how important resistance exercise is for our overall health. Stronger and larger muscles take up and burn more energy or calories, help minimize our risk of falling as we age and also help us recover faster from surgery or injuries following a fall.
The muscles that matter most in a “bang for your buck” kind of way are going to be your lower body. So exercises like squats, hip-hinging movements like dead lifts, and weighted carries like a farmers walk. Even for individuals who will not be doing those exercises if they are advanced in age or injured; getting out of a chair without using your arms, calf raises, and other body weight movements are what you should be concentrating on. Upper body exercises should be performed too to develop your overall skeletal muscle, but you should absolutely emphasize leg exercises.
B. Putting fewer simple carbohydrates 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 carbohydrates 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 triglycerides in your body that your liver produces.
What’re simple carbohydrates? (White) bread, rice, cookies, and any added sugar. This can be a daunting issue for many. Literature continues to get published and clear findings are beginning to emerge. Those already with glucose issues, insulin resistance or even Type II Diabetes are at a much greater advantage for more normalized glucose levels as the day progresses, when eating a meal first thing in the morning with a high protein meal and complex carbohydrates. Yes, that means Breakfast! In a recent Review, the authors investigated the difference in post-prandial (after meal) glucose regulation and blood levels in general throughout the day in individuals. Due to many people eating the majority of calories in the late afternoon and evening, this study was initiated to look at how meal timing might influence this. The results indicated that both glucose and insulin signaling are the highest first thing in the morning and slowly decline as the day goes on, being lowest (less insulin sensitive) in the evening. This suggests that the old adage of eating like a king for breakfast, a popper for dinner certainly makes sense.
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 and increasing our general daily activity is also very important. If you’re already thinking that running, cycling or other activities like this are something you WILL NOT be doing, what other strategies can we employ to increase your movement activity each and every day?
You’ve probably heard the little tips and tricks around parking further away from the front door in a parking lot, taking the stairs instead of the elevator and maybe even some quick breaks throughout the day at your desk for other types of activity. All of these are excellent ideas, but they really have a lot of validity behind them.
D. Sleep !!
Yes, sleep. Sleep is CRUCIAL to our overall health and wellbeing. Below is a list of diseases that are not caused by or worsened by a lack of proper sleep.
1…..
Okay, it’s true though… Sleep is very important for our bodies and our minds. We are a chronically under-slept society and I’m throwing myself completely out there on this one. Sleep is a passive process. Nothing too sexy about it. 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 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 tools (both mindset based and physical) available to improve our chances to get a full 8 hours sleep.
There are other posts out there on the web regarding the benefits of sleep and neurodegenerative disease prevention, but sleep also improves how our body manages blood sugar and insulin levels by different mechanisms. Our brain has an influence on our liver via the vagus nerve. The better slept and rested your brain, 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.
Understanding how our bodies work to influence our health is empowering. Hopefully this information helped you understand how your food intake, exercise, and sleep patterns can influence your risk of developing insulin resistance and Type 2 Diabetes.
You have the power to change this.
As always, don’t forget to keep your doctor in the loop. It’s always important to speak with your doctor about changing your diet, and exercise if concerned about possible underlying or present issues you might be facing.