What you need to know about insulin resistance

Insulin is an essential hormone that we cannot live without. What happens, however, when it is chronically too high? Our tissues stop responding to it effectively. That’s insulin resistance.

Insulin resistance is a very common condition that often accompanies obesity or a diagnosis of pre-diabetes, type 2 diabetes, polycystic ovary syndrome (PCOS), cardiovascular disease, and other metabolic conditions such as hypertension and non-alcoholic fatty liver disease.

Have you been told you have insulin resistance? You’re not alone.

Studies estimate that up to 45% of the US population and similar numbers in other countries currently have insulin resistance.1 In studies of obese women, more than 70% are insulin resistant and among those with type 2 diabetes, the number rises to over 80%.2

Many people with the condition are unaware that they have it.

Also concerning? Insulin resistance is being linked to an increased risk of some cancers, Alzheimer’s disease, mental health disorders and other chronic conditions.3

So how does insulin resistance start? How do you if know if you are affected? And what can you do about it?

This in-depth guide will explain the science behind insulin resistance, help you understand why it happens and suggest the best way to get the condition diagnosed long before serious conditions like type 2 diabetes develop.

In a second, related guide, “How to reverse insulin resistance”, we will suggest concrete steps you can take to help your body become sensitive to insulin once more, and help prevent metabolic health problems, especially type 2 diabetes, from developing in the future.


What is insulin resistance?

Insulin resistance is when cells in your body do not respond effectively to the hormone insulin that is circulating in your body. This causes the pancreas to secrete even more of this important hormone in an effort to keep your blood sugar stable.

Insulin has many roles. Its primary role is to keep our blood glucose levels in a very tight range — called blood glucose homeostasis. That’s because both too high and too low blood glucose levels are dangerous and damaging to the body. When glucose levels rise, more insulin is secreted. When glucose levels fall, less insulin is secreted. In general, keeping insulin in a low physiologic range may be better for your long-term health.

Insulin also enables glucose to be used by cells for fuel or stored as glycogen in muscle and liver cells. Falling levels of insulin let the liver know when to make more glucose (gluconeogenesis) and rising insulin levels let the liver know when to stop.

Another crucial role is insulin’s regulation of fat storage. When insulin levels are high, it stimulates fat cells to take up glucose and turn it into fat (lipogenesis). Then, when insulin is low, it enables the body to take the fat out of storage and use it for energy.4

For someone who is metabolically healthy, this process works seamlessly to ensure a constant supply of fuel for the body. The problem arises when we are not metabolically healthy, which some researchers estimate may be the case for as many as 88% of Americans.5

When our bodies are exposed to an unrelenting supply of glucose, insulin is constantly secreted and remains chronically high — a condition called hyperinsulinemia.6 That is when our bodies stop responding properly to insulin’s signals.7


Why does insulin resistance happen?

Genetic risk factors, environmental risk factors, and lifestyle factors have all been found to contribute to the development of insulin resistance.8

While some people may be genetically more likely to develop insulin resistance, the biggest impact has perhaps come from the change in our food environment in recent decades. Greater availability of cheap, energy-dense food and drinks may have led whole populations to adopt an unhealthy lifestyle, characterised by consumption of high levels of sugar and other refined carbohydrates. These are broken down into large amounts of glucose that we may not need for energy, perhaps resulting in some of it being stored in our cells.

One way of looking at how insulin resistance develops is to consider that over time, the body may have been constantly bombarded by this excess glucose so long that the liver and muscle cells become completely “full” of glucose. Since they are full, they literally can’t take in any more. However, the constant supply of glucose into the blood from high carbohydrate meals requires that the glucose must go somewhere. Thus, the battle ensues between the body’s cells and its pancreas.

The pancreas secretes more insulin to tell the cells that the level of glucose in the blood is too high, and that they need to take in more glucose. The cells cannot respond because they are full, so they resist letting glucose enter. The pancreas then goes into overdrive, secreting even more insulin in an attempt to overcome the cellular resistance and force the glucose into the cells.

Some rightly argue that chronic hyperinsulinemia is the better term for this worsening physiologic condition rather than insulin resistance. The muscle and liver cells are not really “resistant” to insulin, it is just that they are full and cannot respond, despite the pancreas’s escalating efforts. As Dr. Jason Fung has said, it’s like trying to put more clothes into a completely full suitcase. The suitcase isn’t “resistant” to clothes. It is simply full.


Symptoms of insulin resistance

Insulin resistance has no obvious symptoms of ill health.

The main symptom of the condition in many people — prior to being diagnosed with pre-diabetes or full-blown type 2 diabetes — is increasing abdominal fat, although not everyone will be aware of this.9

A prevailing theory of how insulin resistance worsens is that we each have a threshold level of fat that can be stored in our fat cells and when this is exceeded, our body starts storing fat in less ideal places — especially around the organs in our abdomen (such as the liver and the pancreas) and in our abdominal cavity. This is called visceral fat and when this fat starts increasing, it is a sure sign of insulin resistance.10

Other subtle signs of insulin resistance in some people are dark, dry patches of skin on the groin, armpits, or back of the neck, known as acanthosis nigricans.11 Skin tags — small fleshy growths — often on the neck or armpits can also be a sign of insulin resistance in some people, which is thought to occur because insulin is a stimulator of cell growth.12

Other than those symptoms, most people with early insulin resistance feel fine. It is only as blood glucose finally starts to rise that other symptoms of high blood sugar and type 2 diabetes may begin to show, such as frequent urination, excessive thirst, fatigue, and excessive hunger.

It is important to understand that insulin levels climb higher and higher in an attempt to keep blood glucose under control. For a while, this works. But eventually higher insulin levels may fail to compensate entirely, and blood glucose levels start to rise. This may not happen until late in the disease process.

By the time someone is diagnosed with type 2 diabetes, they have probably had insulin resistance — or chronic hyperinsulinemia — for a number of years, perhaps even more than a decade.


Conditions associated with insulin resistance

The following health conditions are associated with insulin resistance:

  • Obesity — Insulin resistance is associated with high insulin levels that may lead to increased body weight and obesity; obesity in turn leads to increased insulin resistance, thus creating a vicious cycle13
  • Pregnancy — Many women show signs of insulin resistance during pregnancy, especially in the third trimester14 This is believed to be an evolutionary adaptation to provide sufficient glucose to the rapidly growing fetus. However, in some people, this can lead to gestational diabetes and high blood pressure.15 This appears to be a good example of how a normal adaptation designed to help ensure healthy pregnancy make us more susceptible to metabolic disease in the context of our modern lifestyle with foods high in refined carbohydrates and sugars.
  • Metabolic syndrome — This describes a collection of characteristics that are found in people with insulin resistance. There are a number of different definitions for metabolic syndrome that usually include an elevated fasting blood glucose level, high blood pressure, raised triglycerides and reduced HDL cholesterol, and increased waist circumference.16
  • Pre-diabetes — Insulin resistance is associated with pre-diabetes. This is a situation where blood glucose levels are higher than normal but not yet high enough to diagnose type 2 diabetes. The World Health Organisation defines pre-diabetes as a fasting glucose of 110 – 125 mg/dL (6.1- 6.9 mmol/L) or an HbA1c of 6% (42 mmol/mol) or above. The US and some other countries use a different definition (FBG above 100mg/dL (5.7mmol/L) or HbA1c above 5.7% (39 mmol/L). Since a diagnosis of pre-diabetes depends on an elevated blood glucose level, it implies that insulin levels have been chronically elevated for some time before the diagnosis.
  • Polycystic ovary syndrome (PCOS) — Polycystic ovary syndrome (PCOS) is a common metabolic disorder affecting up to 10% of women of childbearing age. It’s a leading cause of infertility, and increases the risk of developing type 2 diabetes in later life.17 Women with PCOS tend to have elevated levels of male hormones, irregular or absent menstrual periods, and cysts on their ovaries, as well as insulin resistance. Other common symptoms are obesity, acne, male-pattern hair loss, and excess facial and body hair. 18
  • Non-Alcoholic Fatty Liver Disease — Called NAFLD, this is where there is too much fat stored in the liver. It may be the result of chronically high insulin levels and it may contribute to insulin resistance. While it is more common in individuals who are obese, who have metabolic syndrome, or who have type 2 diabetes, it has been found to be associated with insulin resistance and hyperinsulinemia in lean individuals with normal glucose tolerance.19 Some people with NAFLD go on to develop liver problems, such as inflammation, scarring, and cirrhosis as well as liver failure.20
  • Cancer — Insulin resistance is associated with an increase in risk of colorectal cancer, endometrial cancer, pancreatic cancer, and breast cancer.21 It is not clear whether it is the insulin resistance itself or its relationship to other risk factors, such as obesity and high blood glucose, that contributes to the increased cancer risk. However, it is thought that chronically high levels of insulin may promote cancer growth and that reducing insulin levels may slow cancer growth, although more data is needed in this area to draw firm conclusions.22
  • Cardiovascular disease (CVD) — Insulin resistance and hyperinsulinemia are associated with increased risks for cardiovascular disease, in part because it is so closely associated with other CVD risk factors such as obesity and hypertension.23 Some studies suggest, however, that insulin resistance is an independent risk factor for heart disease.24 There are a number of theories on why hyperinsulinemia could trigger progressive heart disease. Most of them center around increased chronic inflammation and oxidation as well as direct vascular damage.25
  • Alzheimer’s disease — Recent evidence suggests that Alzheimer’s disease could also be linked to insulin resistance.26 Studies show that those with diabetes are 60% more likely to develop dementia.27 Another study shows an increased prevalence of brain changes in those with diabetes.28 Although the exact mechanism is not proven, the theory is brain cells become insulin resistant and then cannot use glucose efficiently for fuel, thus leaving the cells starving for energy. The result is eventual progression to Alzheimer’s disease.
  • Adaptive insulin resistance — Eating very-low-carb diets has been associated with a condition called adaptive insulin resistance (also sometimes called physiologic insulin resistance or adaptive glucose sparing.) It is not known how this happens but it is possible that if we stop eating sugar or carbohydrates, the amount of glucose in our blood will fall. Our body will make sure, however, that our brain gets the glucose it needs by not taking up as much glucose into the liver, fat cells or muscle cells (thus those cells become “insulin resistant”). The muscle and liver cells instead use ketones for fuel. Since this type of insulin resistance occurs with low rather than high levels of circulating insulin, it is not felt to represent the same dangerous condition as regular insulin resistance and may actually be a good thing.


Diagnosing insulin resistance

How do you know if you have insulin resistance? What tests can you have that will confirm the diagnosis?

Unfortunately, insulin resistance is rarely diagnosed in most medical practices. It’s not because it isn’t widely prevalent in society, but because doctors don’t generally order the tests for it. This may be because tests for insulin levels are expensive and not available in all locations.

Instead, doctors more often order the standard tests for diabetes that measure glucose levels: fasting blood glucose and hemoglobin A1c. However, by the time these are raised, insulin levels have likely been high for years, if not decades.

What can you test if you don’t want to wait until pre-diabetes or type 2 diabetes develops?

That’s simple: measure your waist and your height!

Waist-to-height: a powerful predictive measure

One of the earliest symptoms of insulin resistance is an expanding waistline as the body stores fat in your abdomen.

Even people with “healthy” body mass index numbers between 20 and 25, can have fat collect in their abdomens if they are becoming insulin resistant. This situation is sometimes called TOFI — thin on the outside, fat on the inside. The fat is literally wrapping itself around the liver, heart, kidneys, pancreas and other organs.

That’s why the size of your waist in relation to your height will tell you a great deal about your insulin sensitivity. Greater abdominal circumference in relation to height is related to an increased risk of diabetes, hypertension, cardiovascular disease and overall mortality even in people of normal weight.29 While this isn’t a perfect test, it is very easy to do, does not require your doctor to order it, and it can give you a good starting point to see if you have insulin resistance.

To get your ratios you just divide your waist measurement by your height. A waist-to-height ratio less than 0.5 indicates good insulin sensitivity, while a number higher than 0.5 indicates worsening insulin resistance.

You don’t even need a tape measure. Just take a piece of string! The length of string around your waist should be at most half your height. If your waist is larger than half your height, you likely have insulin resistance.

One of the great strengths of this measurement is that it doesn’t matter what your ethnicity, whether you are male or female, young or old, short or tall, muscular or wiry: a number higher than 0.5 indicates an increased risk.30

Many health campaigns are now encouraging this simple idea: “keep your waist to less than half your height.”

Chart your waist and height

UK researcher Dr. Margaret Ashwell has pioneered the use of the Ashwell Shape Chart, which shows colored zones for waist-to-height measurements.

This simple graph can show you the danger zones. Just chart your waist measurement against your height and you can see where you fall in the graph.

Ashwell

Working with your doctor

As noted, most doctors don’t routinely test for insulin resistance. They wait instead for pre-diabetes or type 2 diabetes to develop.

However, armed with the results of your waist-to-height ratio, if it is larger than 0.50, you can talk with your doctor about ordering follow up tests to confirm that insulin resistance is present, and that you are at risk for blood sugar and metabolic problems.

You will likely have to ask for these tests. Don’t be afraid to be proactive and educate your doctor about these tests if you request them, as they are well worth the effort. However, be aware that not all health systems provide tests for insulin levels and you may have to pay the full cost yourself.

The top two tests we recommend are:

  • Fasting insulin and fasting triglycerides. With this test, a blood test is taken first thing in the morning before you have eaten. Your insulin levels and your triglyceride levels are then measured. Triglycerides are a routine test that are easy to do, but fasting insulin, on the other hand, is less commonly ordered and you will likely have to ask for it specifically. One study showed these tests had the strongest association with insulin resistance.31 Since fasting insulin by itself is only really helpful if very high (>20) or very low (<3), combining a mildly elevated insulin with elevated triglycerides (>150) enhances the sensitivity, making insulin resistance much more likely.
  • HOMA-IR- Homeostatic Model Assessment for Insulin Resistance. This is a fancy name for a simple test of both your fasting blood glucose and fasting insulin levels.32 It takes those two results and plugs them into a special calculator and gives you a numeric result. The concept is simple: How high does your insulin need to be to maintain your fasting glucose level? As an example, a fasting glucose of 95 mg/dL (5.3 mmol/L) with an insulin of 3 gets the HOMA-IR number of 0.7, suggesting good insulin sensitivity. But that same fasting glucose with an insulin level of 27 gets the HOMA-IR number of 6.3, suggesting clear insulin resistance and hyperinsulinemia. Any HOMA-IR number under 1 suggests good insulin sensitivity, while over 1.9 indicates early insulin resistance and anything over 2.9 indicates significant insulin resistance.

Summary

Awareness of and testing for insulin resistance, even with a simple waist-to-height measurement, should be more common among doctors and patients. If we wait for a rise in blood glucose, then we could have missed years of high insulin levels that could have been reversed.

Instead, we want to identify insulin resistance early so we can reverse it and prevent the dangerous consequences of metabolic disease.

If you have confirmed insulin resistance, a number of proven lifestyle changes may be effective to help reverse the condition, including a low-carb or ketogenic diet, exercise, sleep, stress reduction and tobacco cessation. Check out our in-depth insulin resistance treatment guide for more detailed information.

/ Dr. Bret Scher, MD



Comments

  1. Journal of Diabetes Research 2015: Population-based studies on the epidemiology of insulin resistance in children [observational study; weak evidence]

    Advances in Preventive Medicine 2016: Prevalence and associated factors of insulin resistance in adults from Maracaibo City, Venezuela [observational study; weak evidence]

  2. Minerva Endocrinology 2012: Prevalence of metabolic syndrome and insulin resistance in overweight and obese women according to the different diagnostic criteria [observational study; weak evidence]

    Diabetes 1998: Diabetes. 1998 Prevalence of insulin resistance in metabolic disorders: the Bruneck Study [prospective cohort study; weak evidence]

  3. Journal of Clinical Endocrinology and Metabolism 2001: Insulin resistance as a predictor of age-related diseases [prospective cohort study; weak evidence]

  4. Clinical Biochemist Reviews 2005: Insulin and insulin resistance [overview article; ungraded]

  5. Metabolic Syndrome and Related Disorders 2019: Prevalence of optimal metabolic health in American adults: national health and nutrition examination survey 2009–2016 [observational study; very weak evidence]

  6. Diabetes 2012: Banting lecture 2011 hyperinsulinemia: cause or consequence? [overview article; ungraded]

    Journal of Endocrinology 2017: A causal role for hyperinsulinemia in obesity [overview article; ungraded]

  7. Clinical Chemistry 2018: Genetic evidence that carbohydrate-stimulated insulin secretion leads to obesity [mechanistic study; ungraded]

  8. Clinical Biochemist Reviews 2005: Insulin and insulin resistance [overview article; ungraded]

  9. One reason people may not be aware of this is the condition called TOFI, i.e. thin on the outside, fat on the inside. This means fat is stored inside the abdomen, where it may not be very visible from the outside.

  10. Biochimica et Biophysica 2010: Adipose tissue expandability, lipotoxicity and the metabolic syndrome — an allostatic perspective [overview article; ungraded]

  11. American Journal of Clinical Dermatology 2004: Acanthosis nigricans associated with insulin resistance: pathophysiology and management [overview article; ungraded]

  12. Dermatologic Therapies (Heidelberg) 2017: Skin manifestations of insulin tesistance: from a biochemical stance to a clinical diagnosis and management [overview article; ungraded]

  13. Journal of Clinical Investigations 2000: Obesity and insulin resistance [overview article; ungraded]

  14. American Journal of Clinical Nutrition 2000: Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus [overview article; ungraded]

  15. Journal of Clinical Endocrinology and Metabolism 2003: Insulin resistance and its potential role in pregnancy-induced hypertension [overview article; ungraded]

  16. One definition of metabolic syndrome is as three or more of the following markers:

    • Fasting blood glucose above 100mg/dL (5.5 mmol/L)
    • Elevated triglycerides above 150mg/dL
    • High density lipoproteins (HDL) below 40mg/dL in men and 50 in women
    • Elevated blood pressure above 130/85
    • Increased abdominal obesity with a waist circumference over 40 inches in men and 35 inches in women.

    All of these characteristics tend to be common in insulin resistance as well.

  17. Clinical Epidemiology 2014: Epidemiology, diagnosis, and management of polycystic ovary syndrome [overview article; ungraded]

  18. Journal of Diabetes and Metabolic Disorders 2018: Lean polycystic ovary syndrome (PCOS): an evidence-based practical approach [overview article; ungraded]

  19. American Journal of Medicine 1999: Association of nonalcoholic fatty liver disease with insulin resistance [case-control study; very weak evidence]

  20. Reviews on Recent Clinical Trials 2014: Non alcoholic fatty liver: epidemiology and natural history [overview article; ungraded]

  21. Trends in Endocrinology and Metabolism 2010: The proliferating role of insulin and insulin-like growth factors in cancer [overview article; ungraded]

    Oncogenesis 2017: Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway [mechanistic article; ungraded]

    Endocrine Related Cancers 2015: Highly specific role of the insulin receptor in breast cancer progression [mouse study; very weak evidence]

  22. Endocrinology 2011: Minireview: IGF, insulin, and cancer [overview article; ungraded]

  23. New England Journal of Medicine 1987: Insulin resistance in essential hypertension [mechanistic study; ungraded evidence]

    British Medical Journal Open Heart 2017: Added sugars drive coronary heart disease via insulin resistance and hyperinsulinaemia: a new paradigm [editorial; ungraded]

  24. New England Journal of Medicine 1996: Hyperinsulinemia as an independent risk factor for ischemic heart disease [prospective-cohort study; very weak evidence]

  25. Cardiovascular Diabetology 2018: Association between insulin resistance and the development of cardiovascular disease [overview article; ungraded]

    Circulation 2002: Insulin causes endothelial dysfunction in humans [randomized trial; moderate evidence]

    Reviews in Endocrine & Metabolic disorders 2013: Role of insulin resistance in endothelial dysfunction [overview article; ungraded]

  26. Journal of Diabetes, Science and Technology 2008: Alzheimer’s disease is type 3 diabetes – evidence reviewed [overview article; ungraded]

  27. Diabetes Care 2016: Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia [systematic review of observational trials; weak evidence]

  28. Neurology 2015: Type 2 diabetes mellitus and biomarkers of neurodegeneration [mechanistic study; ungraded]

  29. BMJ Open 2016: Waist-to-height ratio as an indicator of ‘early health risk’: simpler and more predictive than using a ‘matrix’ based on BMI and waist circumference [retrospective observational study; very weak evidence]

  30. Obesity Reviews 2014: Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis [strong evidence]

  31. Diabetes Care 2001: Diagnosing insulin resistance in the general population [mechanistic study; ungraded]

  32. Diabetologia 1985: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man [mechanistic study; ungraded]