by Gabriel Ariciu, DC

Sorry, but the answer is not 42. My last article was on Alzheimer’s and Lyme disease. I wanted this one to focus on Alzheimer’s and insulin resistance, but I felt compelled to broaden it’s scope. I’ll start by breaking down insulin resistance and then venture into the destruction it leaves in its wake. I will conclude with strategies to overcome insulin resistance and lead a healthy lifestyle.

What is Insulin?

Insulin is a hormone. Without it we will die. It is essential but it is also problematic in today’s society. Most of the time when we think about Diabetes, we think blood sugar. But long before blood sugar goes haywire, insulin activity is rising higher and higher.

Insulin is produced by the beta cells of our pancreas. Type 1 diabetics know this all to well, because their beta cells have been destroyed due to autoimmunity. This is why they are insulin dependent, they must use an exogenous source for insulin. Otherwise, they cannot utilize glucose properly. That is one of the main functions of insulin. It is the hormone that is responsible for feeding and storing. It is released in response to eating carbohydrates and protein. Insulin binds to receptors on our cell membranes to allow glucose into the cells. The cell membrane is a barrier or a wall separating the cell from its external environment. We use glucose to make adenosine triphosphate or ATP which we in turn use for energy. ATP is made through glycolysis (our anaerobic metabolic pathway) and oxidative phosphorylation (our aerobic metabolic pathway). We make a lot more ATP through oxidative phosphorylation. Just an interesting tidbit, but very important when we discuss fatty acid metabolism and metabolic efficiency. Remember, without insulin the glucose breakdown cannot happen. Without glucose, energy production is compromised and we will die. Type 1 diabetes used to be fatal until the discovery of insulin. Now understand glucose is not our only means of energy and most of our cells can thrive off of fat instead, however there is one cell that cannot, erythrocytes, our red blood cells. They do not have mitochondria, our cells’ little energy factory, therefore they can only make ATP using glucose.

Another aspect of insulin is that of storage. When we have adequate energy from glucose, insulin signals the the production of glycogen in our liver and skeletal muscle. We can store about 500 grams or so. Once those stores are filled up we start the process of lipogenesis, fat storage. This is an important part to remember. If you want to make someone fat, you give them insulin. There are other diseases that promote fat production such as hypothyroidism, but hyperinsulinemia is by far the biggest culprit. Let me break this down a little further.

Insulin:Glucagon Ratio

We have established insulin is necessary, but how much is needed? Is carbohydrate or glucose breakdown our only means of energy production? As I said earlier insulin spikes when we consume carbohydrates and protein. Let me talk about protein for a minute. Protein is considered insulinogenic, but there is a major caveat to this statement. The ratio of glucagon and insulin must be looked at too.

Glucagon is a hormone with the opposite effects of insulin. Remember, insulin is the hormone of feeding and storing, whereas glucagon is the hormone of fasting and burning. In skeletal muscle tissue, insulin acts to promote glycogen production and protein synthesis. Glucagon has no effect on skeletal muscle, because there are no receptors for it. In adipocytes (fat cells), insulin acts to create more fat, whereas glucagon promotes the breakdown of fat. In the liver, insulin promotes the production of fat and glycogen. When you think lipogenesis in the liver, you should also be thinking of fatty liver disease which is a major problem today. Finally, glucagon promotes glycogen and fat breakdown, creation of new glucose (gluconeogenesis), and ketones.

Obviously the ratio of insulin:glucagon is weighted towards insulin in skeletal muscle since glucagon has no effect. But with adipocytes both act upon them, but insulin seems to have a stronger effect. The opposite is true with the liver. Glucagon will win.

What about macronutrients and this ratio? With carbohydrates insulin increases, and glucagon decreases. Fat increases glucagon only (big win for fat and against the mainstream thought I might add!). Protein depends on context and this is very important. A cursory glance at protein makes it seem like it raises both insulin and glucagon, but it depends on the glycemic state. In hyperglycemia states (high levels of blood sugar) protein is shown to increase insulin levels. But in a fasted state, protein has no significant effect on insulin. This is important in a fasted state. If you were to have a insulin spike your blood sugar would drop and you would pass out and quite possibly die. One last thought on protein, when someone eats the Standard American Diet (SAD diet) their insulin:glucagon ratio is fairly high around 4 or so. But when protein is consumed with the SAD diet the ratio skyrockets to around 70! Before you point a finger at protein, think of this, when protein is consumed with someone on a low-carb diet, insulin doesn’t spike. In fact, those who eat low-carb tend to have a low insulin:glucagon ratio.

So what is all this telling us? High insulin:glucagon ratio promotes feeding and storing, and low insulin:glucagon ratio promotes fasting and burning. We can rule out fat which has no effect on insulin. Protein can also be ruled out because it only increases when blood sugar is high and blood sugar is high when we eat carbohydrates. So that leaves us with just carbohydrates as the culprit. It is the main reason for high insulin states. So let’s talk about the Standard American Diet.

The SAD Diet

The diet of meat and potatoes, the diet of junk food, the diet driven by fast food and convenience. It is a diet of high carbohydrates. Pasta, breads, muffins, donuts, crackers, chips, french fries, etc. Often times our meals will include more than one, take a burger with fries, you have bread and potatoes. Sandwiches almost always include more than one.

I will admit they are delicious, but that is part of the problem. It activates the mesolimbic pathway in our brain, our reward system. We eat a burger and fries most likely with a Coke (more sugar) and dopamine floods in making us feel amazing. Of course we want to feel that way again, so we splurge again and again. This of course feeds certain bacteria in our gut more than others promoting a stronger drive to eat more sugar. Please understand this point, all carbohydrates are sugar. That doesn’t make them inherently bad, but we need to be careful with them because of the culture we created around them.

Unfortunately, the dietary recommendations have not helped this issue. The war on fat started in the 1950s because of a faulty study that associated fat with heart disease. This has driven the high carbohydrate, low fat theory for decades. It has become a standard. If you remember the food pyramid before it was replaced, it had the majority of our foods coming from grains and carbohydrates. Low fat foods became a craze, in fact, it is still difficult to find certain foods like yogurt without them being low-fat. What has happened since the 1950s? Heart disease, diabetes, and obesity have skyrocketed! So it is not just the SAD diet but also our dietary recommendations that have caused the epidemic of obesity and insulin resistance.

Hyperinsulinemia

As we eat more carbohydrates our insulin spikes increasing glycogen storage, protein synthesis in the skeletal muscle, and formation of fat in the liver and adipose tissue. The more we consume the more insulin is produced. But after a time our cells grow resistant to insulin. And it takes more insulin to store the same amount of glucose. There is a down regulation of insulin receptor sites. Imagine your cell membranes are the walls around a city. The gates can only be opened by insulin to allow glucose in and there are 50 gates. As hyperinsulinemia occurs, remember that means high insulin in the blood, your cells begin to shutdown the gates. So over time, your gates will decrease from 50 to 40, to 30, and so on. The decrease means you are getting less glucose in and your body creates more insulin to counter that effect. After a period of time when enough gates are shutdown blood sugar starts to rise. Blood sugar levels should stay below 100, ideally 90. But with the down regulation of these receptors blood sugar has no where to go so it stays in the blood. This is typically when prediabetes and diabetes are diagnosed. This is years after insulin has been spiking regularly. So in a sense, the diagnosis is very late on the scene. After a period of time the pancreas will burnout and insulin production will decrease. This results in higher blood sugar levels leading to insulin injections being prescribed. It is a terrible state of affairs at that point. Now let’s turn our attention towards the deleterious effects of high insulin and blood sugar on the body.

Hyperinsulinemia, Hyperglycemia, and the Body

I mentioned that insulin and carbohydrates are the main culprits, but a word on other factors that cause insulin resistance. Environmental toxins such as diesel exhaust, cigarette smoke, BPA, and many other toxins cause insulin resistance. They do this by creating inflammation just as obesity does. Inflammation is a major cause of insulin resistance. So anything that creates inflammation causes you to become insulin resistant. This includes food intolerance and chronic infections. Stress is another major player. Our body’s response to stress is to release cortisol. Cortisol promotes gluconeogenesis (creation of new glucose from protein and fat), breakdown of glycogen, and is anti-inflammatory. Essentially when mama bear is chasing you, you want all the energy necessary to run away. Creation of glucose stimulates the pancreas to release insulin. Chronically high cortisol puts us into a highly inflamed  state (more insulin resistance) where we are susceptible to all sorts of problems including one we will talk about later and that is memory loss and neurodegeneration.

Insulin resistance has been linked to fatty liver, cancer, PCOS, sarcopenia, osteoarthritis, heart disease, and of course, diabetes. These are terrible diseases that are very prevalent. Most commonly we think about diabetic issues such as neuropathy, retinopathy, nephropathy, delayed healing, and cardiovascular issues.

An important biochemical pathway called the polyol pathway (creation of fructose from glucose) is enhanced during hyperglycemic states leading to a decrease in glutathione, our body’s primary antioxidant. Glutathione is needed to protect against oxidative stress and inflammation.

There is also an increase in advanced glycation end products (AGEs). These are implicated in cardiovascular issues such as plaquing and arteriosclerosis. It also promotes the oxidation of LDL cholesterol which leads to further inflammation in our arteries and heart disease. AGEs inhibit nitric oxide thereby diminishing our ability to dilate our blood vessels. They also increase the production of cytokines which are proinflammatory.

Microvascular changes arise with hyperinsulinemia and hyperglycemia. There is a reduction in peripheral perfusion. Not only nervous tissue but also in the skin. Nerve ischemia results leading to neuropathy. Your blood supplies the needed the nutrients and if nerves cannot get the nutrients they cannot maintain themselves. This is why many diabetic patients have loss of feeling in their feet and delayed healing. Foot ulcers are quite common. Retinopathy is quite similar due to the microvascular changes, damage to vision results. I have witnessed first hand the end stages of diabetes as a nurse. One patient had her leg amputated and the other leg was not far from it. I remember trying to put an IV in and the skin was very tough. But it doesn’t end here.

The kidneys become damaged over time due to the oxidative stress and AGEs. This leads to impaired renal function and dumping of needed molecules such as albumin, a protein in our blood important for many biological processes. Kidneys are watched very closely in uncontrolled diabetes.

As you can see the effects are many and varied. Now I will turn our attention to the brain and the nervous system. (1)

The Effects of Hyperinsulinemia on the Brain

I have already talked about neuropathy caused by microvascular changes. The same issues stated above increase the risk of stroke too. Arterial plaquing and inflammation stress the cardiovascular system which can lead to stroke, both ischemic and hemorrhagic.

In hyperinsulin and hyperglycemic states there is sensitization of the CNS that happens too. Hyperactivity of spinal neurons can result in altered pain perception. This can make you feel hypersensitive and increase the amount of pain you are experiencing. It is an important player in pain control, fibromyalgia, and other chronic pain issues. (1)

High states of inflammation and stress are damaging to our body, most especially the hippocampus. The hippocampus is a region of the brain and has an important role in learning and memory, converting short term memory into long term. It regulates our circadian rhythm. Due to having many receptors for cortisol, the hippocampus his highly effected by high levels of cortisol. It is not uncommon for people have memory issues and sleep problems during episodes of high stress. When stress is chronic neurodegeneration sets in.

In response to the inflammation, microglial cells are activated. They release further cytokines in our brain resulting in more inflammation. In states of chronic inflammation, microglia are shown to damage neurons, exacerbate the degradation of tau protein, and activate neurotoxic astrocytes. (2) If this sounds familiar, it should. This is essentially describing the environment that creates Alzheimer’s disease. Furthermore, if you remember from my last article, there are certain things that activate the formation of amyloid beta plaques. High insulin and inflammation are big ones.

This is why Alzheimer’s disease is often referred to as type 3 diabetes. It is strongly linked to it. And as you can see the effects of insulin resistance are tremendous and devastating. It behooves us to know where we stand and to make the needed changes. Prevention is key.

How Do You Know if You are Insulin Resistant?

  • Do you have fat around your belly?
  • Do you have high blood pressure or a family history of heart disease?
  • Do you have high triglycerides?
  • Do you have gout?
  • Do you retain water easily?
  • Do you have a family member with type 2 diabetes?
  • For women: Have you had gestational diabetes or PCOS?
  • For men: Do you have low testosterone?
  • Have you been diagnosed with a fatty liver?
  • Do you have skin tags or dark sections of skin?

About 50-90% of people with insulin resistance are undiagnosed. Some who are lucky may be diagnosed with metabolic syndrome which has certain criteria, some of which are mentioned above. Metabolic syndrome is a combination of conditions that increase your risk for heart disease, stroke, and diabetes. It is a preventative diagnosis. Prevention is key and that is why regular testing and getting checkups are so important. We stress this with every patient. We like to see our patients at least every 6 months. Some more often depending on the case. Blood work really helps nail down what is going in the body. In addition to this is being tested by a practitioner certified in Applied Kinesiology. I have learned over time certain challenges and tests with muscle testing that can accurately evaluate the status of each patient and how they are holding up metabolically. It is a crucial part of our evaluation and treatment process that increases our accuracy and effectiveness.

Testing

The most common tests that are done are HbA1c (which measures your blood sugar over the last 3 months), fasting glucose, and oral glucose tolerance test. HbA1c is the gold standard. However, we are trying to diagnose insulin resistance and all these tests look at blood sugar. They are late in the game. We need to get out of the mode of thinking that diabetes and insulin resistance is a blood sugar problem. Blood sugar tests are clinically relevant and important markers, but blood sugar doesn’t start rising until long after insulin resistance has set in. We are trying to catch insulin resistance early, so we need to look at insulin.

Fasting insulin needs to be ran. This is essential but let’s have a look at the numbers. When you see the normal reference range for insulin it is broad and not very helpful. If you are not familiar with reference ranges it is the range your blood work needs to be in to be considered “normal”. However, often times these numbers are not indicative of normal. In fact, many people have symptoms and problems with “normal” labs. That is why I narrow the range on many labs to what I call a functional range. That range is more typical of normal health.

Insulin has a range of 2.0-19.6 µIU/ml. For an adult who is fasting the range is 2.00-5.00 µIU/ml.

  • Normal: up to 5
  • Prediabetes: 7-17
  • Diabetes: 17 or above

It needs to be done fasting. Several studies have shown the importance of this blood marker. One study in the Lancet, Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up studyshows insulin issues 10 years before there are any blood sugar issues. 10 years! That is huge in the realm of prevention. Another study suggests that “only the fasting insulin level should be used as a marker of insulin resistance.”

What to do now

Seek out a competent practitioner. I highly recommend those who look in depth, someone with a functional medicine and applied kinesiology background. We are trained to ask questions that no one else does and to investigate deeper. Manual muscle testing sets us apart and helps us to accurately, effectively, and efficiently treat. We run the necessary blood work as well. So I would advise looking for someone that offers these services, but ultimately the choice is yours. But I don’t want to leave you hanging, let me share some options that you may want to try. As always this is not to be taken as medical advice.

Whole food diet. Eating from one ingredient foods that are organic and locally grown. Find a farmer’s market, go to a farm, google it, whatever you need to do, but get some good resources for food. If it comes in a box or a bag don’t buy it. Protein sources need to be from animals that have been pasture raised or grass-fed. This is step one.

Step two. Adopt a low-carb diet. How low depends on your situation. If you want to lose weight, keep the carbs under 100g per day. If you are diabetic or prediabetic a more restricted course is recommended. Cycling in and out of ketosis is a good start. Ketosis is a process by which our body produces ketones for energy. Ketones are produced from fat. Basically, you move from using glucose as your primary energy source to fat. Work with your healthcare practitioner on this one if you are diabetic so they can monitor your case. If you choose this course the first couple of weeks can be tough as you make the switch. There is something called the keto flu. You may get headaches and tired among other things. If this happens it may very well be a mineral deficiency. So some Himalayan salt or mineral water can be very helpful.

Here are some of the benefits you may have:

  • Promotes insulin sensitivity
  • Autophagy
  • Lipolysis (good bye fat!)
  • Brown adipose tissue activation (highly metabolic and good for burning excess energy aka fat)
  • Conversion of white adipose tissue to beige (acts like brown fat)
  • Improved memory and cognition
  • More energy
  • Reduction in symptoms related to insulin resistance

Step three. Intermittent fasting. Our ancestors often went without food. Many religions utilize fasting as a part of their teachings. Fasting is an important part of increasing insulin sensitivity. When we fast our body must shift to burning glycogen and fat. Intermittent fasting has been shown to improve cognition, promote fat loss, lower insulin and blood sugar levels, increase growth hormone, lower blood cholesterol, promote autophagy, and reduce inflammation. It is quite simple too. There are two forms that I like: time restricted and alternate day fasting.

Time restricted fasting means you only eat within a given time period. 16:8 is very common where you only eat within a 8 hour time window each day without snacking in between meals. 18:6 is also popular with a 6 hour time window. Alternate day fasting means that you do a 24 hour fast every other day. This means you eat normally one day with breakfast, lunch, and dinner, and then the next day you only eat dinner making it 24 hours. It is up to you how often you want to do this, but at least a couple of times per week is recommended unless you are insulin resistant. Then like with the low-carb diet, consult with your healthcare practitioner and see what is best for you. I often recommend the time restricted fasting. I myself follow the 18:6.

Well that’s it. You may be thinking, that’s it? This is long! Where is the tl;dr version. Sorry, the information is too good to reduce and too good to not share. I hope this gives you some avenues to go down or maybe just some food for thought!