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

Insulin resistance affects 4-in-10 adults and leads to metabolic syndrome, diabetes, heart disease, diabetes, dementia and death. But what causes insulin resistance and what can you do about it?

Written by

Dr Alasdair Scott MBBS FRCS PhD

gut doctor, PhD and our research director


Key Takeaways

  • 4-in-10 adults are insulin resistant, requiring more insulin to control their blood sugar.
  • Insulin resistance is caused by fat build up in the muscles, liver and pancreas which prevents normal insulin signalling and reduces insulin production.
  • Insulin resistance causes weight gain and metabolic syndrome.
  • Exercise can reverse insulin resistance.

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.

What is insulin resistance?

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.

How does insulin reduce blood glucose levels?

  • Stimulates cells, particularly muscle, liver and fat cells, to put “glucose transporters” into their cell membranes so they can take up more glucose.
  • Stimulates glycolysis - burning of glucose for energy
  • Stimulates production of glycogen, a storage form of glucose
  • Promotes formation of fat from glucose (lipogenesis) in the liver and fat cells
  • Prevents fat break down (lipolysis) and fat burning in mitochondria (oxidation)
  • Prevents gluconeogenesis - formation of new glucose in the body

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”.

What causes insulin resistance?

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.

Insulin-resistant individuals cannot get glucose into the muscle for it to be turned into glycogen.

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!

Who gets insulin resistance?

We see insulin resistance in lean, non-obese people in their 20s

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:

Risk factors for developing insulin resistance

  • Physical inactivity
  • Energy imbalance - more in than out
  • Being overweight
  • Ageing
  • Family history - e.g parents or siblings with insulin resistance
  • Medications - e.g. steroids
  • Pregnancy
  • Black, hispanic or Native American ethnicity

Why is insulin resistance a problem?

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.

Higher levels of insulin resistance have been shown in numerous studies to be strongly associated with an increased 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:

The five features of metabolic syndrome

  • Obesity
  • High blood pressure
  • High triglycerides
  • Low HDL-cholesterol
  • High fasting glucose

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.

What can you do to reverse insulin resistance?

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

Exercise can reverse insulin resistance

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.

Exercise is probably the most powerful tool we have to reverse insulin resistance.

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.

Carbohydrate restriction can help

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.

To sum up

Insulin resistance might just be the most important threat to your health and longevity, but it's under your control.

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…

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