Insulin resistance and why we should all know more about it

Blood sugar or blood glucose is a topic that we hear more and more about, whether from family and friends or the media. Most people are aware of the importance of keeping their blood sugar in a healthy range, some have even used Continuous Glucose Monitors (CGMs) to see how different foods impact them. Less well known is the role of insulin and its importance for everyone, not just diabetics. The aim of this article is to help you understand why insulin is important and what you can do to support a healthy insulin response.

What is insulin?

Let’s start by going back to basics. Insulin is a hormone (produced by your beta cells in your pancreas) that regulates the amount of glucose in your bloodstream. The discovery of insulin in 1922 marked a breakthrough in diabetes treatment. Diabetes has a long history (first described in 522 BC in Egyptian medical texts) but until the discovery of insulin, those with diabetes had short lives.

What does insulin do?

After a meal, glucose is released into your bloodstream. In response, your pancreas releases insulin. Insulin binds to insulin receptors on your cell membranes and signals to your cells to let the glucose in, thus lowering blood glucose back to safe levels. The cells that respond to this insulin signal are skeletal muscle cells, liver cells and fat cells. Skeletal muscle is the most important, accounting for about 75% of glucose disposal. The message from insulin is store and/or use glucose in order to get it out of your bloodstream.

When there’s excess glucose (such as after a carbohydrate-heavy or sugar-rich meal), some cells (in the adipose tissue (fat), liver and pancreas) have the ability to take the surplus glucose and store it as fat. In the liver, this increases the risk of non-alcoholic fatty liver disease (NAFLD) and in the pancreas it interferes with the beta cell function and their ability to produce insulin.

What is insulin resistance?

What happens when the cells don’t respond as they should to the insulin signal? This is called insulin resistance. If you think of insulin as a person knocking on a door. When the door opens, glucose is able to leave your bloodstream (where too much is harmful) and enter your cells. If someone has good insulin sensitivity they will “hear” the knock and open up. However, if they’re insulin resistant, they’ll “ignore” the knock and it’ll need to be louder before they open the door. As the years go by and they become increasingly insulin resistant, the knock will have to be louder still, leading to higher and higher insulin and glucose levels. Then, as the beta cells become worn out, blood glucose remains continuously high and prediabetes or Type 2 diabetes develops. Chronically elevated blood glucose has been shown to damage blood vessels and can lead to an increased risk of, among other things, cardiovascular, kidney, nerve and eye issues.

It’s estimated that insulin levels can start to rise 10-15 years before the development of Type 2 diabetes. This gives us a window of time to intervene with diet and lifestyle changes before a diagnosis is reached. Further support for early intervention comes from a 2023 UK longitudinal study looking at nearly 2000 people (with and without Type 2 diabetes). The authors suggest that, in the 25 years leading up to diagnosis, there’s “an early phase of inflammation-related disease activity.” In their study, hypertension was most common, but cases of ischaemic heart disease, kidney issues and asthma also increased.

Insulin also plays an important role in brain health, and it’s thought that insulin dysregulation could contribute to neurodegeneration. Insulin resistance means that the brain cells fail to respond to insulin, which can lead to cognitive issues. Research is ongoing into how insulin dysregulation impacts Alzheimer’s disease. It’s interesting that centenarians tend to have low insulin levels and high insulin sensitivity!

How to measure insulin resistance?

The hyperinsulinemic euglycemic clamp (HEC) is the gold standard for assessing insulin resistance but it’s complex (involves an intravenous insulin drip), and only used in small scale research.

• High blood glucose or HbA1c. Fasting glucose can be a useful indicator, especially when it’s above the normal reference range (Hemoglobin A1c (HbA1c) of 48mmol/mol (6.5%) or more indicates persistent hyperglycaemia, whereas non-diabetic hyperglycaemia refers to blood glucose levels that are above normal but not in the diabetic range (HbA1c 42-47 mmol/mol (6.0-6.4%)) . (HbA1c) is a measure of average blood glucose over the previous two-three months, and is a helpful predictive marker for pre-diabetes, which is how it’s practically applied in clinical practice to enable earlier intervention to prevent progression of the condition.
  
  A French study looking at how to identify early on those who are at high risk of diabetes found that HbA1c was able to predict diabetes in their cohort of over 2,500 men and women (aged 30-65 years). According to Diabetes UK, should your HbA1c level be between 42-47 mmol/mol (6-6.4%), it’s higher than normal and you’re at risk of developing Type 2 diabetes. However, the American Diabetes Association classify prediabetes as 5.7-6.4%. Although you may be told your HbA1c is fine according to current NHS standards, if it’s higher than 5.6%, you may wish to seriously consider making lifestyle changes to reduce your risk.

The following are simpler ways for testing for insulin resistance well in advance of some of the markers currently used. However, many of them haven’t found their way into mainstream routine clinical practice in the UK yet as an early predictor of insulin resistance. That being said, anyone can access a paid-for fasting insulin test from many professionals in the integrative health community, private doctors or using a services like Medichecks, for example.

• HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) is a calculated measure: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. It’s often used in clinical practice as a good surrogate for insulin resistance and has a strong correlation with HEC. However, it cannot be used in people receiving insulin treatment or those with non-functioning beta cells (in your pancreas), i.e. in those with type 1 diabetes or advanced insulin-dependent Type 2 diabetes.

• FIRI (Fasting insulin resistance index) and QUICKI (Quantitative insulin sensitivity check index) are also formulas based on fasting plasma concentrations of glucose and insulin. Research shows that HOMA-IR, FIRI and QUICKI all provide a good alternative to HEC.

• Fasting Insulin is often used as a practical way of detecting insulin resistance before a clinical disease appears. Research shows that an elevated fasting insulin is an independent predictor of developing Metabolic Syndrome over a five-year period.

• The Triglyceride Glucose (TyG) index is a useful surrogate measure, especially in countries where resources are limited and insulin isn’t routinely tested. It has been shown to be a good measure of insulin resistance in both those with and without diabetes. It’s calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2).

• TG/HDL (triglyceride to HDL-Cholesterol) is widely used as a surrogate for Metabolic Syndrome and insulin resistance. Whilst a high triglyceride / HDL-Cholesterol ratio is associated with insulin resistance in some normal-weight healthy adults, it’s worth remembering that this isn’t valid for all ethnicities. A 2010 study found that it wasn’t appropriate for African Americans.

It should be noted that, whilst insulin resistance is the main cause of hyperinsulinemia, in rare cases it can be caused by an insulin producing tumour.

Potential signs of insulin resistance:

Darkening of the skin. Acanthosis nigricans is a velvet like darkening of the skin, which usually occurs in skin fold areas, such as the back of the neck, groin and armpit. It’s most commonly associated with insulin resistance and diabetes.

Obesity. Excess adiposity, as measured by either body mass index or waist circumference, increases the risk of insulin resistance for several reasons:

• Adipose tissue secretes proinflammatory molecules which increase systemic inflammation and promote further adipose tissue. This leads to increased levels of C- reactive protein, a non specific marker of inflammation associated with several metabolic and cardiovascular conditions. Not all obese individuals develop insulin resistance but over 80% of cases do.

• When insulin levels are high, it sends a signal to the body to store fat. It does this by inhibiting lipolysis (the process through which fats are broken down) and by stimulating lipogenesis (the process of producing fatty acids and triglycerides (a type of fat called lipid) in the liver and fat tissue). The balance between lipolysis and lipogenesis determines fat build up.

High blood pressure. There seems to be a bidirectional relationship with some research showing that high blood pressure may contribute to insulin resistance and some showing that insulin resistance may contribute to high blood pressure. Both are impacted by factors, such as stress, physical activity, endothelial function and inflammation. The endothelium is a single layer of cells that line your blood vessels and lymph vessels. Insulin is important for endothelial function and the production of nitric oxide, which is crucial for maintaining healthy blood pressure.  

High uric acid. Traditionally associated with gout, but more recent research is showing a link to metabolic health. A 2021 study in adults at risk for Type 2 diabetes found that high serum uric acid is significantly associated with insulin resistance. Another paper found that, as insulin resistance increases, the body’s ability to clear uric acid is reduced. Uric acid can be measured at home using an inexpensive finger prick meter. 

High triglycerides. A 2020 paper found that triglyceride levels were independently correlated with insulin resistance and high levels had a negative effect on beta cell function. A Swedish study, which followed 1,351 middle-aged women for 18 years, found that “even very slightly elevated triglycerides resulted in a considerably enhanced risk of developing diabetes.” Low HDL cholesterol is often seen with high triglycerides and thought to be a useful long term predictor of insulin sensitivity.

Family history. For anyone with a family history of diabetes, a history of polycystic ovarian syndrome or gestational diabetes, it’d make sense to check the possibility of insulin resistance. Family history is important and research is ongoing into genes that play a role in insulin resistance and metabolic syndrome.

How to reduce insulin resistance: Lifestyle measures to improve insulin sensitivity

Increase your physical activity. Just about any type of physical activity can improve insulin sensitivity with high intensity exercise having an even greater impact on insulin levels. Who would have thought that even a single session of resistance exercise can help? Remember, skeletal muscle is responsible for the vast majority of glucose use, so strength/resistance exercise is likely to be effective support for glucose use and, so should theoretically aid blood glucose regulation. One small study on 12 healthy males found that just one session of resistance exercise improved insulin sensitivity for up to 24 hours. It’s important to maintain muscle mass as we age. The more muscle we have, the more glucose we can safely use.

How much of your day is spent sitting? Sedentary behaviour is a known risk factor for many chronic health conditions. A 2017 systematic review, which included over 1.3 million global participants, found that there was a particular threshold above which risk for several health outcomes rose more rapidly. If you sit for more than 6-8 hours / day, and watch television for more than 3-4 hours / day, you may want to think about reducing this. The link to television watching isn’t just the hours spent sitting, but also likely to be due to the poor food choices that often go hand in hand with watching television. The study found that, for Type 2 diabetes in particular, any reduction in time sitting was beneficial. Even a small amount of movement can help with small studies showing that leg fidgeting can help improve glucose control after meals in people with obesity.

Aim for at least seven hours of sleep every night. A recent systematic review suggested a significant association between sleep deprivation and insulin resistance. The exact mechanisms aren’t clear, but even a single night of poor sleep can have an impact. One small study found that sleeping for 4.25 hours compared to 8.5 hours led to significantly impaired fasting insulin sensitivity in a group of healthy men.

Find ways to reduce stress as chronic stress has been associated with insulin resistance. There are many stress reduction techniques including mediation, breathing exercises and walking in nature. Find one that works for you.

Consider your toxic load and take steps to reduce it. We’re constantly exposed to potentially harmful substances through air, food and drink, home furnishings and cleaning products. A recent paper looked at persistent organic pollutants (a type of chemical which doesn’t degrade) and found a “modest correlation between exposure to these chemicals and diabetes risk.” These chemicals have been found in the human pancreas where they cause changes in beta cell function. The Environmental Working Group’s Clean 15 and the Pesticide Action Network (PAN) UK’s Dirty Dozen are good starting points for low pesticide fruit and vegetables. Home air filters can be helpful if the air quality around your home is poor.

“Insulin resistance diets”: dietary changes can have a powerful impact:

We talked about lipogenesis (fat synthesis) earlier and how it’s stimulated by high insulin levels. Research shows that lipogenesis is very responsive to changes in diet. A high carbohydrate diet will stimulate lipogenesis but fasting, polyunsaturated fatty acids and a low carbohydrate diet will suppress it.

Low carbohydrate diet. Dr David Unwin is a GP based in the North West of England. For the last eight years, he has used a low carbohydrate diet to achieve drug free Type 2 diabetes (T2D) remission in 20% of his T2D patients. For those in the first year of a T2D diagnosis, an astonishing 77% achieved remission. A systematic review and meta analysis also suggested a beneficial effect of low carbohydrate diets on blood control in patients with Type 2 diabetes.

Ketogenic diet. A 2020 meta-analysis found that the ketogenic diet was effective for improving insulin resistance (measured by HOMA-IR) in patients with Type 2 diabetes.

Eat for your gut bacteria. Whilst our understanding of the gut microbiome continues to evolve, very recent research has identified particular gut bacteria associated with insulin resistance and insulin sensitivity. A 2023 meta-analysis found that probiotic supplementation had “favourable effects on glycaemic control in T2DM patients” and led to a “significant reduction in insulin levels.” Those taking a food-type probiotic (e.g. yoghurt and kefir) saw a greater reduction than those taking a probiotic supplement. So, including a wide variety of fermented foods in your daily diet can be beneficial.

Include Intermittent Fasting. The term Intermittent Fasting covers several different types of fasting including alternate day fasting, time restricted eating, periodic fasting and alternate day modified fasting. It has many benefits, including weight loss and improving insulin sensitivity. A simple way to start is to aim to have a fasting window of 12 hours every night. For example, if you finish eating your evening meal at 7pm then have nothing but water until 7am the following day.

Spice things up. Herbs and spices have long been used to support health as well as providing delicious flavours. Some, such as cinnamon, clove, cumin, fenugreek, ginger, liquorice, marjoram, nutmeg, oregano, rosemary and turmeric, are well known for their anti-diabetic activity. A 2019 review found that over 900 compounds from herbs and spices had potential anti-diabetic activity. Natural compounds that have been shown to improve insulin sensitivity include curcumin (turmeric), garlic and polyphenols (from colourful fruit and vegetables). Ginger has many benefits including for insulin resistance. A 2014 small randomised controlled study in patients with Type 2 diabetes, found that daily consumption of 3g ginger powder led to an improvement in insulin resistance in just eight weeks.

Think about how you cook your food. Advanced Glycation End Products (AGEs) are found in many highly processed foods but are also formed by cooking at high temperatures. If you bake, roast, fry or grill you produce more AGEs than boiling or steaming. One small study done in Australia found that a diet low in AGEs increased insulin sensitivity in healthy overweight individuals. To encourage healthy insulin sensitivity, boil or steam food wherever possible, but note that steaming, rather than boiling food like vegetables, helps maintain the nutrient density of the food.

Currently, over 500 million people live with diabetes globally and it’s estimated that this will increase to more than 1.3 billion by 2050. Type 2 diabetes accounts for the majority of cases. Insulin resistance is the main driver for both metabolic syndrome and Type 2 diabetes. We know that there is a window of opportunity of 10-15 years before a diagnosis is reached. During this time, insulin levels gradually creep up unless diet and lifestyle changes are put in place. Early intervention would not only benefit the health of many, but also reduce the vast global cost of diabetes treatment.

Reviewed by:

Anna Keeble MA BA Head of Content and Wellbeing Expert

Dr Claire Marie Thomas MRCGP DFSRH DTMH DipNLP MBChB BMedSci Medical Expert

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