Insulin resistance: causes, symptoms, and treatment

If you’re on this page, you may have recently come across the term “insulin resistance” and are hoping to learn more. Perhaps you’re traveling down an internet rabbit hole and somehow ended up here. More likely, you’ve heard the term in the context of diabetes, and now you want to discover what exactly it means and if it may be affecting you.

In short, insulin resistance is exactly what it sounds like - it’s a condition in which your body becomes resistant (or less sensitive) to the hormone insulin. Fully understanding what this means and how it can affect your body, though, depends on an understanding of what insulin even is, to begin with. Once we’ve covered that, we can get back to insulin resistance.

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Insulin is a hormone in the body that is produced by the pancreas, an organ that sits behind your stomach. The pancreas has specialized regions called the islets of Langerhans, and these are where hormone-secreting cells lie. Specifically, there are cells called beta cells in the islets of Langerhans, and the beta cells are the ones that make insulin.

Insulin is one of the main hormones in the body that helps regulate blood sugar levels (also called blood glucose levels). Usually, blood sugar levels go up after you eat food that has sugars or carbohydrates. In response to elevated blood sugar levels, insulin is released from the beta cells into the bloodstream. Insulin then lowers blood sugar levels by doing the following:

• It helps fat cells take up glucose, which can be stored as triglycerides (a type of fat)

• It helps liver cells take up glucose, which can be stored as glycogen (a chain of sugars)

• It helps muscle cells take up glucose, which can be used for energy or stored as glycogen to be used for energy later

Diseases in which insulin does not work are, therefore, diseases in which the body cannot regulate blood sugar. These include type 1 diabetes mellitus (T1DM), in which the pancreas stops making insulin, and type 2 diabetes mellitus (T2DM), in which the body still makes insulin, but the body does not respond to it as well. This is called insulin resistance and is what we’re talking about in this article. So let’s get back to that.

Insulin resistance occurs when the body’s cells have decreased insulin sensitivity. In insulin resistance, the pancreas still secretes insulin in response to elevated blood sugar levels, and insulin still flows around the body, attempting to act on fat, liver, and muscle cells. However, for whatever reason, these cells are no longer as good at “listening” to insulin. As a result, they are less efficient at taking up glucose. This can lead to high blood sugar levels (hyperglycemia) and can cause the pancreas to produce even more insulin to compensate for the resistance (leading to hyperinsulinemia, which means high blood insulin).

Some people’s bodies may do just fine compensating for insulin resistance. However, in many people, the pancreas eventually loses the ability to keep up with the demands of the body. When this happens, blood sugar levels begin to rise. When blood sugar levels remain partially elevated, an individual is said to have prediabetes. When blood sugar levels stay above a certain threshold, the individual is said to have T2DM. The fasting plasma glucose (FPG) test and the oral glucose tolerance test (OGTT) are tests that can be used to diagnose these two conditions. This means that insulin resistance is the cause of T2DM. However, while all people with T2DM have insulin resistance, not all people with insulin resistance develop T2DM. It all depends on how effective your body is at dealing with insulin resistance. In addition to T2DM, insulin resistance increases the risk of cardiovascular disease (heart disease and blood vessel disease), polycystic ovary syndrome (PCOS), obesity-related cancers, and metabolic syndrome.

Besides T2DM, insulin resistance is often talked about in combination with the metabolic syndrome. The term “metabolic syndrome” refers to a group of conditions that are each a risk factor for developing T2DM and/or cardiovascular disease (heart disease and blood vessel disease). Metabolic syndrome is also sometimes referred to as “syndrome X.” Components of the metabolic syndrome include:

• Excess belly fat or an enlarged waistline (central obesity)

• High blood pressure (hypertension)

• High blood sugar (hyperglycemia)

• High levels of fat in the blood (hypertriglyceridemia)

• Low levels of “good” cholesterol (low HDL)

To be diagnosed with metabolic syndrome, you must have at least three of the five components. According to the NIH, the metabolic syndrome is associated with excessive blood clotting and low levels of constant inflammation in the body (NIH, n.d.). Similar to insulin resistance and T2DM, inactivity, and being overweight or obese are potential causes of metabolic syndrome. It may also be influenced by age (your risk increases as you get older) and genetics (including your family history). Metabolic syndrome is a lifelong diagnosis, but lifestyle modifications and medications can help control its components.

Perhaps one of the most frustrating things of all is that researchers don’t entirely know what causes insulin resistance. While we have been able to identify specific things that put you at increased risk, the actual mechanism by which insulin resistance manifests has remained elusive. That being said, the most significant contributors are:

• Excess weight, particularly in the abdomen: Having an increased amount of fat in the abdomen (this is called central obesity) and around the organs (this is referred to as visceral fat) is a risk factor for insulin resistance. Even if your body mass index (BMI), which is a ratio of your weight to your height, is in the normal range, men who have a waist size ≥40 inches and women who have a waist size ≥35 inches are more likely to have insulin resistance. Asian individuals are more likely to develop T2DM, so the at-risk waist size cutoffs are even lower: ≥35.5 inches in men and ≥31.5 inches in women (ADPI). Researchers believe these fat cells release inflammatory markers known as adipocytokines or adipokines, which may play a role in the development of insulin resistance.

• Sedentary lifestyle: Not getting enough physical activity each day is linked to insulin resistance.

There are also non-obesity related causes of insulin resistance (UpToDate, 2018).

These include:

• Certain medications: Medications that have been implicated in insulin resistance include steroids (e.g., prednisone), some antipsychotics, some HIV medications, and oral contraceptives.

• Certain medical conditions: Medical conditions that affect hormones can lead to insulin resistance, including Cushing’s syndrome (high levels of cortisol) and acromegaly (high levels of growth hormone).

• Pregnancy: Hormones associated with pregnancy, including placental lactogen, can play a role in developing insulin resistance. This may lead to gestational diabetes in susceptible women.

• Other issues with fat: Conditions of abnormal distribution of fat (lipodystrophy) or fat loss (lipoatrophy) can cause severe insulin resistance.

• Type A insulin resistance: This is due to genetic conditions that cause a problem with the insulin-signaling pathway.

• Type B insulin resistance: This is due to antibodies that block insulin receptors.

• Other inherited diseases: Leprechaunism and Rabson-Mendenhall syndrome are rare conditions in which the insulin receptors are mutated, causing insulin resistance.

Some people do not have any symptoms of insulin resistance at all. Others may only realize they are insulin resistant when they receive a diagnosis of prediabetes or T2DM. In individuals who have diabetes and uncontrolled blood sugar levels, symptoms may include:

• Increased thirst (polydipsia)

• Frequent urination (polyuria)

• Extreme hunger (polyphagia)

• Lack of energy

• Weight loss

• Vision changes

• Numbness, tingling, or pain in the extremities

• Difficulty healing

• Recurrent infections

There may be additional signs that somebody has insulin resistance that is not directly related to T2DM. These include:

• Darkening of the armpits and neck (acanthosis nigricans)

• Skin tags

• Baldness (alopecia)

• Absence of menstrual periods (amenorrhea) or infertility in women

• Excess hair growth in women

• Issues with fat tissue (loss or overgrowth), muscle tissue (cramps or overgrowth), or growth (impaired or increased) (UpToDate, 2018)

Healthcare providers do not routinely check for insulin resistance. More commonly, insulin resistance is discovered during a screening blood test for diabetes. Diabetes screening tests include the FPG test, the OGTT, and the hemoglobin A1c (HbA1c) test. One study suggests that checking fasting insulin levels and fasting triglyceride levels can be useful for identifying insulin resistance (fasting means not eating or drinking anything for at least eight hours) (Mcauley, 2001). However, when making the diagnosis of insulin resistance, healthcare providers typically just consider how a patient clinically looks and whether they have other health conditions that usually occur alongside insulin resistance (e.g., high blood pressure and abnormal cholesterol levels). More specific tests may be done in those who appear to have an inherited form of insulin resistance.

Because insulin resistance can lead to several issues, including cardiovascular disease and T2DM, it is crucial to take steps to reverse it. Insulin resistance is primarily managed by making lifestyle changes. Two of the most important things that an individual can do to reverse insulin resistance include losing weight and becoming more active. According to the American Diabetes Association, losing just 7% of body weight can help with insulin resistance (ADA, 2009). Additionally, it is recommended that everybody engage in at least thirty minutes of moderate exercise at least five times a week.

If you have already been diagnosed with T2DM, there are several medications that you can take to make you more sensitive to insulin. One of the most commonly prescribed medicines is metformin (brand name Glucophage). Metformin can also be prescribed for those with prediabetes to help prevent the progression into T2DM. However, this is an off-label use (meaning it is not an FDA-approved use of the drug).

If you have insulin resistance due to one of the rarer, genetic causes, management of your condition may be more involved and should be discussed with your healthcare provider.

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Current version

August 26, 2019

Written by

Mike Bohl, MD, MPH, ALM

Fact checked by

Tzvi Doron, DO

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About the medical reviewer

Tzvi Doron, DO

Dr. Tzvi Doron is Board Certified in Family Medicine by the American Board of Family Medicine.