What is insulin resistance, why is it a problem and what can you do about it?

We humans are simply not adapted to live in the modern world. We were forged in the fires of starvation and rose to the top of the evolutionary pile because of our ability to store energy and keep our hungry frontal cortices fed with glucose.

Unfortunately, we’re now paying the price in our energy-rich, sedate environment. What once kept us alive is now a driving force behind the major diseases of our time - heart disease, diabetes, cancer and dementia. And it all begins with insulin-resistance.

In this deep-dive we’ll go through what insulin resistance is, why it matters and what you can do about it. If you need a little refresher on what happens in your body when you eat carbohydrate, check out our recent article on glucose metabolism.

If you have insulin resistance (IR), it means that the cells in your body are not able to respond to the hormone insulin as well as they should. It’s important to understand that IR isn’t an “all or nothing, you either have it or you don’t” problem. IR is a spectrum from “insulin sensitive” through “so mildly insulin resistant you can hardly tell” to “so resistant to insulin that your pancreas is exhausted, you have diabetes and you’re having to inject insulin 5 times a day”.

Hopefully you’ll remember that insulin is a hormone produced by your pancreas in response to glucose in your blood (if not, check out our article on glucose metabolism). Insulin has many functions but chief amongst them is to reduce blood sugar which it does in a couple of ways.

If you have IR, your cells need more insulin to metabolise a given amount of glucose than someone who doesn’t have insulin resistance. For example, someone without insulin resistance might need 1 “unit” of insulin to control their blood sugar after drinking a Coke. In comparison, someone with insulin resistance might need 3 “units”.

Your muscles are one of the major sites of insulin-stimulated glucose disposal (up to 70-80%) so it’s no surprise that IR begins at the level of the muscle. We have two problems occurring. First, consumption of more calories than we expended results in fat generation. Fat is initially stored under the skin but eventually spills over to be stored in the muscles, liver and other organs. At the same time ageing, a sedentary lifestyle and possibly inherited factors damage the ability of muscle mitochondria (the powerhouses of muscle cells) to oxidise (burn) fat¹.

Excess production and reduced ability to burn fat leads to fat build up inside the muscle cells. This disrupts the normal signalling pathways used by insulin to trigger glucose transporters to join the muscle cell membrane². Insulin-resistant individuals cannot get the glucose into the muscle for it to be turned into glycogen.

Because the muscles can’t take up glucose it’s shunted to the liver instead where it’s converted to fat (triglycerides). This results in fat build up in the liver cell, so called “metabolic-associated fatty liver disease”, and high levels of triglycerides in the blood. Fat accumulation in your liver makes your liver resistant to insulin too. Insulin resistance in your liver prevents the conversion of glucose to glycogen and even increases the generation of more glucose through gluconeogenesis³.

To add insult to injury, fat build up in the pancreas is toxic to the cells which secrete insulin (beta-cells) and stops them producing insulin properly. Now you have insulin resistance and impaired ability to secrete insulin and you’re on a sure-fire path to diabetes.

We’ve entered a vicious circle in which fat build up, first in muscle and then the liver and pancreas, is driving worsening insulin resistance, impaired insulin production, increased fat generation and reduced fat breakdown. To break the cycle, you need to lose fat, the one thing your body is no longer geared up to do!

Insulin resistance isn’t something that happens to someone else. It happens to you or people like you. Roughly 40% of adults are insulin resistant ⁴. What’s more, we see insulin resistance in lean, non-obese people in their 20s⁵.

There are several risk factors for developing IR:

So you need more insulin to dispose of glucose, so what? Why’s that a problem? We can dive into the details but the bottom line is this: higher levels of insulin resistance have been shown in numerous studies to be strongly associated with an increased risk of death, from any cause (“all cause mortality”)^{6, 7, 8}. What’s more, this holds true independently of the link between insulin resistance and diabetes. So even without having diabetes, simply being insulin resistant increases your risk of death.

But why? An individual with IR might have a totally normal fasting glucose level but be producing a significant amount more insulin than normal to keep their glucose under control. The trouble with high insulin is that, as we discussed above, it’s also turning off fat breakdown - lipolysis - and stimulating fat formation - lipogenesis. Increased insulin levels (hyperinsulinaemia) are driving weight gain. Studies have shown that only small increases in baseline insulin production are enough to turn off fat breakdown⁹.

Aside from increased fat deposition, hyperinsulinaemia also has effects on blood vessels, inflammation, the kidneys and cholesterol that ultimately result in a collection of problems known as metabolic syndrome (or more enigmatically, “syndrome X” as it was once known). The five features of metabolic syndrome are:

Metabolic syndrome plays a causal role in all the major killers of our time: heart disease, stroke, diabetes, fatty liver disease, cancer and dementia. And it all starts with insulin resistance.

When it comes to reversing IR, you have two levers you can pull - exercise and diet.

Just as IR begins in the muscles, it can be treated there too. In fact, exercise is probably the most powerful tool we have to reverse insulin resistance. Studies have shown that even one bout of aerobic exercise is enough to reverse insulin resistance in sedentary individuals and to increase insulin sensitivity even further in non-IR individuals¹⁰.

More recently, a study found that a bout of exercise in IR-individuals before a carbohydrate-rich meal increased muscle glycogen synthesis threefold and reduced the production of fat in the liver by a third compared to the same meal without exercise beforehand¹¹.

There are a couple of reasons why exercise has this effect. In the short term, exercise stimulates muscles to take up glucose without insulin, so called insulin-independent glucose uptake. Exercise also “unblocks” the insulin-dependent placement of glucose transporters in the muscle cell membrane that was blocked by intramuscular fat in insulin-resistant individuals. In the longer term, exercise increases the number and function of muscle mitochondria which are responsible for burning fat for energy. The muscle can then use fat appropriately rather than have it mess with insulin signalling. Lastly, increases in muscle size and muscle fibre number increase the capacity for glucose disposal.

Although there is ongoing debate regarding the relative roles of high carbohydrate or high fat diets in causing insulin resistance, we have good evidence that cutting down on carbs can help reverse it¹². Although glucose may not be the primary cause, insulin resistance is a problem of glucose-handling and limiting the “glucose burden” by reducing carbohydrate intake is well-established as one of most powerful tools to reduce blood glucose levels¹³. In addition to improving glucose control, low-carbohydrate diets promote weight loss and reduce liver and pancreatic fat storage.

The specifics of low carbohydrate diets are beyond the scope of this article but broadly they involve cutting total carbohydrate intake to under 130g per day or even under 50g per day in very low carbohydrate diets. Regardless of total dietary carbohydrate intake, IR-individuals would benefit from avoiding refined carbohydrate, ultra-processed foods and fructose (particularly in juices), all of which are associated with insulin resistance.

Insulin resistance might just be the most important threat to your health and longevity. More than simply being the first step on the path, it’s the engine that drives you to metabolic syndrome, heart disease, cancer and dementia. It’s also a key window into your metabolic health - if you’re showing signs of insulin resistance, you need to act. Do not wait until you have metabolic syndrome. The good news is that reversing insulin resistance is under your control. All you have to do is move…