The Real Cause of Insulin Resistance – Not Sugar!

You have probably heard of the term insulin before as it is often associated with Diabetes Mellitus. However, many people do not know the many functions of this powerful peptide hormone. Contrary to popular belief, insulin is not your enemy. Insulin is absolutely necessary for life. It is disruptions in insulin that have major negative health consequences. And most doctors don’t know what truly disrupts insulin signaling. Let us tell you know!

What is insulin

Insulin is the main anabolic hormone of the body – which means it helps to build, to grow. Low insulin in the blood has the opposite effect, promoting widespread catabolism – so break down (especially of reserve body fat). We need a balance between anabolism and catabolism. During fasting and sleep your body has time for much needed catabolic activity (repair and regeneration).

Insulin is produced by the beta cells in the islets of Langerhans in the pancreas in response to a high level of glucose in the blood. Glucose is your body’s main — and preferred — source of energy.

Insulin is an energy signaling hormone; it senses metabolic signals, such as glucose, leucine and arginine, and then signals to the brain that there’s enough energy in the blood, so that there’s no need for the liver to start gluconeogenesis (producing glucose) and hunger can be turned off. At the same time, it promotes the absorption of this energy into cells of the liver, fat, and skeletal muscles.

How Insulin Normally Works

When insulin is released into the bloodstream and binds to the glucose transporters (GLUT) of muscles and fat cells, they can absorb glucose from the blood, causing the blood sugar level to drop.

Think of insulin as a key and things like muscle- and fat cells having locked doors that prevents glucose from coming in. Insulin is the key that unlocks millions of cellular doors and allows glucose in the blood to enter these cells.

So you want to be insulin sensitive. Having insulin sensitivity is having clean lock mechanism (the glucose transporters – GLUT) so that the key (insulin) can do it’s work fine.

Now many things can influence the quantity and the quality of these locks; they can get gummed up and insulin will work less well. We call this insulin resistance.

Eventually, the insulin key no longer unlocks the muscle- and fat cells and glucose stays in the blood, causing hyperinsulinemia (and hyperglycemia).

How insulin resistance affects your body

In the case of insulin resistance, glucose and insulin are in the blood, but the insulin sensitivity is impaired, so basically insulin will be absent. The absent insulin provides the opposite signal to the liver: to release stored glycogen and turn it into glucose (gluconeogenesis).

At the same time, the brain continues to produce a feeling of hunger, so that more energy is attracted. After all, the glucose has a hard time getting into the cells. The intensity of the feeling of hunger depends on the degree of insulin resistance; the more insulin resistant you are, the more you’ll want to eat, because will want more glucose to compensate for the insensitivity.

So you keep eating (carbs and fats) and your liver keeps producing glucose, which means you will stay in anabolic mode and glucose and insulin remain raised. You’re not moving enough to use all the the calories you consume, so they have to go somewhere and they are stored in your liver cells, muscle cells, and fat cells (adipose tissue). Your adipose tissue will grow and grow larger, causing inflammation and decreasing insulin sensitivity even more. More on this later.

A self-perpetuating cycle has been created.

At first, you may have no noticeable symptoms of hyperinsulinemia that results from insulin resistance. This is because your pancreas will produce more and more insulin to overcome the resistance. However, chronic raised insulin levels causes inflammation and it’s just a matter of time until it results in prediabetes and ultimately Type 2 diabetes.

And possibly other forms of metabolic dysfunction, such as obesity (but you can also be slim and insulin resistant), metabolic syndrome, Polycystic ovary syndrome (PCOS), atherosclerosis (hardening of the arteries) and Alzheimer.

OK, we’ve laid the groundwork. Now you’re ready to learn the real cause.

What’s the real cause of insulin resistance?

You can ask your doctor, but he or she would probably not be able to explain it to you. They would just say that excess carbs (sugar) causes excess insulin (hyperinsulinemia) causes insulin resistance (and vice versa). That’s it.

The regular treatment is managing the disease by injecting insulin, causing even more hyperinsulinemia. Or a high-fat, low-carbohydrate diet, citing immediate results, but actually these results are disastrous in the long term, and make you *more* insulin resistant.
Or managing the symptom of high blood glucose by prescribing metformin, which only delays or dampens the effects of insulin resistance.

We don’t want to manage disease, we want to treat the root cause. There are many things that can cause insulin resistance, but in this article we want to dive into the biggest one. The one that is not recognized by most doctors – even not by functional medicine doctors.

According to this carbohydrate-centric model, the solution to diabetes is to eat foods that minimize or eliminate your need for insulin, which includes foods that are low carb, high fat, high protein. Following this logic, carbohydrate-rich foods are to blame for high insulin levels.

This model is more than just wrong; it’s an overly simplified attempt at explaining insulin resistance using 1 single variable. Yes, it’s true that fat doesn’t spike your insulin so it can help you to minimize your insulin needs in the short term, but on the long term there’s a different picture.

It’s the fat!

It’s the amount and type of fat that you eat that plays a central role in your ability to control your blood glucose. Failing to fully understand this important connection can dramatically increase your risk for the development of (pre)diabetes and other chronic diseases.

Of course, there are many other causes of insulin resistance, such as genetic susceptibility, lack of exercise, high stress levels, biorhythm imbalance, and excessive alcohol intake, but the largest and most important puzzle pieces are those that relate to the amount and type of food that you eat.

Fatty acids directly inhibit the action of insulin – especially saturated fat. Most people don’t know about this fat-insulin connection, but there’s 100 years of research showing we should adopt a low-fat, plant-based, whole-food diet that is high in natural carbohydrates if we want to optimize our insulin sensitivity.
That’s right, low fat – high carb!

An overwhelming amount of scientific evidence shows that a high-fat diet is the single most effeective method at *inducing* insulin resistance in both your liver and muscle. This is how researchers induce IR in mice in the lab in order to study it.

In the early 1920s, researchers William Sansum and dr. J.Shirley Sweeney were some of the first to publish research about the fat-insulin conncetion. And one of the most important discoveries happened in 1963 when the scientist Philip Randle described that carbohydrate and fat are mutually exclusive fuels, and that fatty acids and glucose compete for entry into cells. He demonstrated that fatty acids gain access to tissues and block insulin from working, leaving glucose trapped in your blood. He called this effect the Randle cycle. It still stands now.

Insulin resistance results from the accumulation of excess dietary fat in tissues and cells that are not designed to store large quantities of fat, which inhibits the action of insulin.

Fatty acids lower IRS-1 tyrosine phosphorylation blocking GLUT4 transporters to get to the cell membrane.

How does this Fat-Insulin Connection work

Fat intake can cause insulin resistance in two ways:

1. Direct pathway

Fatty acids can enter cells without the use of insulin. So you’d think “great! it doesn’t raise insulin”, but here’s the problem: fat enters your blood (via chylomicrons) before glucose, so when you ingest a lot of fatty acids, your liver and muscle cells will uptake it from your blood by upregulating enzymes involved in all aspects of fatty acid metabolism and downregulate enzymes involved in all aspects of glucose metabolism – because fatty acids are now the predominant fuel. When cells in your liver and muscles begin burning and storing fatty acids, just as Randle described, they block glucose from entering because the cellular machinery required to uptake, process and store glucose has been deprioritized. Cells in your liver and muscle alter their internal enzymatic machinery based on the fuel that is most readily available.

How do these cells block glucose from entering? Simple; they stop paying attention to insulin by downregulating insulin receptors (IRS-1) located on the cell surface. Within hours of a single high-fat meal, insulin receptors become less numerous and less functional. So your cells will have a very difficult time recognizing insulin in your blood which means that GLUT4 can’t get to the cell membrane to take the glucose out of the blood and in the cell. Insulin resistance has been created. See the image below.

Checkout this video: https://www.youtube.com/watch?v=fRZduVxlP_U

2. Indirect pathway

As soon as fatty acids are absorbed by cells in your liver and muscle tissue, they are either burned for energy or stored for later use. So the more fat you eat, the more fat you force cells in our liver and muscle to absorb. Your adipose tissue is designed to uptake the surplus of fatty acids and protect tissues like your liver and muscle from accumulating excess fatty acids.

Your adipose tissue is evolutionarily designed to grow and shrink in response to times of feast and famine, but it becomes a problem when fat cells are chronically overfed. Balance between anabolism (feast) and famine (catabolism) is lost. Fat cells cannot expand indefinitely and as they grow and grow, mitochondrial distress increases. The mitochondria in the adipose cells will generate more and more free radicals, resulting in inflammation. Your immune system is recruited to bring a solution, but cannot solve this because the anabolism of the fat cells is chronic. It’s only a matter of time until this results in a chronic low-grade inflammation (LGI).

A LGI means that your immune system will have to stay on, and to be able to stay on it has to ensure that it will get enough energy. Your immune system has many ways to draw precious energy to itself and one important way (where it often starts with) is to make organs (like your liver) become insulin insensitive, which means triggering insulin resistance.

It does this through cytokines (inflammatory messenger molecules) blocking the same IRS-1 as in the direct example above.

Mechanism of fatty acid-induced insulin resistance. Fatty acid metabolites (long-chain acyl-CoA [LCCoA] and diacylglycerol [DAG]), which may accumulate within myocytes because of increased fatty acid delivery or decreased mitochondrial oxidation, trigger a serine/threonine kinase cascade (possibly involving novel protein kinase C, IKK-β, or JNK1). This ultimately induces serine/threonine phosphorylation of critical IRS-1 sites, thereby inhibiting IRS-1 binding and activation of PI 3-kinase, resulting in reduced insulin-stimulated glucose transport.
Source: Mechanisms of Insulin Resistance in Humans and Possible Links With Inflammation

How about the High Fat Ketogenic Diet?

A ketogenic diet is often used as important therapy for diabetes and metabolic syndrome, and it works – on the short term! You keep insulin secretion low, because you keep carb intake low (and protein intake not too high), you will start to produce and use ketones. This helps you feel better and lose weight.

But this all does NOT improve your insulin sensitivity. On a high-fat ketogenic diet, your cells can still be insulin resistant! You just don’t notice it because you’re keeping insulin secretion low. You will notice it though, when you get off the ketogenic diet and start to gain weight faster than ever!

The best way to decrease insulin resistance is by decreasing fat intake. And of course start exercising.

How do you know if you’re insulin resistant?

There are several conditions that might be indicators of insulin resistance are a high BMI, metabolic syndrome, polycystic ovarian syndrome (PCOS) and various cardiovascular diseases (even if you’re not diabetic).

However, you don’t need to be overweight or sick to have insulin resistance. In fact, this is one of the biggest problems with ketogenic and carnivore diets. People may look healthy, but under the surface they suffer from increased insulin resistance.

Insulin resistance often presents as a collection of symptoms including:

• High fasting and post-meal blood glucose
• High fasting and post-meal insulin concentrations
• Weight gain (or an inability to lose weight)
• Low energy
• Impaired digestion
• Inability to think clearly
• A high A1c value (greater than 5.7%)Think of each of these symptoms as symptoms of poor glucose metabolism.

Think of each of these symptoms as symptoms of poor glucose metabolism.

Rising blood glucose levels, a high A1c, or a diagnosis of prediabetes or type 2 diabetes are sure-fire signs of insulin resistance.

You can explore the full list of factors to be aware of on our insulin resistance checklist.

How to Reverse Insulin Resistance Naturally

You can only reverse your insulin resistance is by focusing on increasing your insulin sensitivity and increasing your carbohydrate tolerance. The most powerful way to do this is through lifestyle changes, such as decreasing your fat intake and increasing carb intake.

There are four key tools to reversing insulin resistance:

1. Adopting a diet designed to reduce insulin resistance
2. Daily movement and exercise
3. Managing your stress levels
4. Periodic intermittent fasting

All of which result in other follow-on benefits like weight loss and reduction in belly fat. Let us give you a quick overview if our recommendations:

1. Adopt our Insulin Resistance Diet

The most powerful tool to reverse insulin resistance is by far the insulin resistance diet; a low-fat, plant-based, whole-food diet that is high in natural carbohydrates (carbs) and fiber. Fiber is crucial because it slows glucose absorption and helps stabilize blood sugar levels.

It all makes sense; the main cause of insulin resistance is an excess of dietary fat, so it would make sense that greatly reducing your dietary fat would be fundamental to reversing insulin resistance.

By itself, changing your diet will have an effect that greatly outweighs that of any other potential change. And conversely, without changing your diet, any other lifestyle changes will have significantly less effect.

We recommend keeping total dietary fat intake to about 10-15% of total daily calories, with an emphasis on avoiding animal fats and oils. Fill your plate with vegetables, whole grains and legumes. And eat fruit as much as you like, but eat it alone (not with other foods)!

2. Prioritize Daily Movement and Regular Exercise

Exercise is an excellent way to improve your insulin sensitivity. Both aerobic exercise (like walking, cycling, or swimming) and resistance training (like weight lifting) help your muscles use glucose more effectively. Regular exercise gives your cells the chance to burn excess fat stores. It improves not only your weight and fitness, but also your mood and energy levels.

With a sustained increase in daily exercise, your body also begins to create more mitochondria, which means that your body burns through excess fat stores even faster,

Aim for at least 30 minutes of moderate exercise most days of the week.

3. Managing your stress levels

Since chronic stress can directly cause insulin resistance and keep your blood glucose high, managing stress is essential. Try:
• Mindfulness Practices: Meditation, yoga, or deep breathing exercises can help reduce cortisol levels.
• Time Management: Prioritizing tasks and setting aside time for relaxation can help you maintain a balanced lifestyle.
• Quality Social Connections: Strong social bonds can help buffer against stress.

4. Periodic intermittent fasting

Another tool to help reverse insulin resistance quickly is intermittent fasting, a dietary strategy in which eating periods are interspersed with regular fasts (some times for 16 hours or 24 hours).

The main reason that this works is due to a biological process called autophagy. During extended periods without food, your body uses this natural adaptation to burn excess fat, proteins, and recycled cells for energy. Finally you’re giving your body the chance for much needed catabolism.

Combine these tools together and the results can be powerful. However, it’s important to know what you’re doing as each case of insulin resistance can be different and can have different triggers and mechanisms behind it.

What to do Next

Though these principles are simple, integrating them into your lifestyle can be a big change and can often require guidance and support. You can consider joining one of our programs to dramatically improve your insulin resistance quickly. We guarantee your success!

Summary & Conclusion

Insulin resistance is a silent but significant condition that contributes to various chronic health issues, including weight gain, fatigue, and hormonal imbalance. Left unmanaged, it can escalate to more severe health conditions like type 2 diabetes and cardiovascular disease. However, with lifestyle adjustments—such as a healthy diet, regular exercise, and stress management—you can reverse insulin resistance and significantly improve your quality of life.

Following our method you will be able to eat carbohydrate-rich foods and experience excellent blood glucose control, while simultaneously decreasing your risk for weight gain, obesity, high blood pressure, high cholesterol, coronary artery disease and dementia.

References

1. Effect of free fatty acids on insulin secretion, insulin sensitivity and incretin effect – a narrative review https://doi.org/10.1590/0004-2730000003223 
2. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest. 1996 Jun 15;97(12):2859-65. https://doi.org/10.1172/JCI118742
3. Boden G. Free fatty acids-the link between obesity and insulin resistance. Endocr Pract. 2001 Jan-Feb;7(1):44-51. https://doi.org/10.4158/EP.7.1.44.
4. Santomauro AT, Boden G, Silva ME, Rocha DM, Santos RF, Ursich MJ, Strassmann PG, Wajchenberg BL. Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.
   Diabetes. 1999 Sep;48(9):1836-41. https://doi.org/10.2337/diabetes.48.9.1836.
5. Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training. Compr Physiol. 2013 Jan;3(1):1-58. https://doi.org/10.1002/cphy.c110062.
6. RANDLE PJ, GARLAND PB, HALES CN, NEWSHOLME EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785-9. https://doi.org/10.1016/s0140-6736(63)91500-9
7. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595-607. https://doi.org/10.2337/diab.37.12.1595
8. Koeslag JH, Saunders PT, Terblanche E (June 2003). [“A reappraisal of the blood glucose homeostat which comprehensively explains the type 2 diabetes mellitus-syndrome X complex”](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2342944). The Journal of Physiology.
9. Termannsen A-D, Søndergaard CS, Færch K, Andersen TH, Raben A, Quist JS. Effects of Plant-Based Diets on Markers of Insulin Sensitivity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. _Nutrients_. 2024; 16(13):2110. https://doi.org/10.3390/nu16132110
10. https://en.wikipedia.org/wiki/Insulin
11. Book: Mastering Diabetes – by Cyrus Khambatta, Robby Barbaro