Insulin Resistance

Insulin resistance is a condition where your body’s cells don’t respond properly to insulin, a hormone that helps control blood sugar levels. This complex condition affects millions of people and can lead to serious health problems, but many people can take steps to prevent or reverse it through lifestyle changes.

Table of contents

• What is insulin resistance?
• Who can develop insulin resistance?
• Signs and symptoms
• What causes insulin resistance?
• Related health conditions
• How is it diagnosed?
• Treatment and management
• Prevention and reversal

impaired insulin sensitivity

What is insulin resistance?

Insulin resistance happens when cells in your muscles, fat, and liver don’t respond to insulin as they should^[1]. Insulin is a hormone your pancreas makes that’s essential for regulating blood glucose (sugar) levels^[1].

When you eat food, your body converts that food into sugars that circulate in your blood. Insulin acts like a key to let blood sugar into your body cells, which use the sugar as energy^[2]. After this happens, your blood sugar returns to a normal level. Insulin also signals your liver to store extra blood sugar as energy for later^[5].

When insulin resistance develops, your cells don’t respond well to insulin. This means they can’t efficiently use the glucose for energy or for storage. As a result, glucose continues to build up in your blood^[1]. Your pancreas makes more insulin to try to overcome your increasing blood glucose levels. This is called hyperinsulinemia^[1].

As long as your pancreas can make enough insulin to balance out your blood sugar levels, they’ll stay in a healthy range. If your cells become too resistant to insulin, it leads to elevated blood glucose levels, a condition called hyperglycemia^[1]. Over time, this can lead to prediabetes and Type 2 diabetes^[1].

Who can develop insulin resistance?

Insulin resistance can affect anyone — you don’t have to have diabetes — and it can be temporary or chronic^[1]. The two main factors that seem to contribute to insulin resistance are excess body fat, especially around your belly, and a lack of physical activity^[1].

Certain factors can increase your chances of developing insulin resistance. These include having overweight, obesity, or a large waist size, and being age 35 or older. Children and teens can also develop insulin resistance, but the risk goes up as a person gets older^[3].

Having a family history of insulin resistance, including family members with prediabetes, Type 2 diabetes, or polycystic ovary syndrome, can also contribute to insulin resistance^[1]. Insulin resistance should be suspected in patients with a history of diabetes in first-degree relatives, patients with a personal history of gestational diabetes, polycystic ovary syndrome or impaired glucose tolerance, and obese patients, particularly those with abdominal obesity^[7].

People who are African American, American Indian, Asian American, Hispanic, or Latino have a higher risk of insulin resistance^[3]. Other risk factors include high blood pressure, high cholesterol, history of gestational diabetes, history of heart disease or stroke, having a sleep disorder like sleep apnea, and smoking^[3].

People who have prediabetes and Type 2 diabetes usually have insulin resistance. People with Type 1 diabetes can also experience insulin resistance^[1].

Signs and symptoms

If you have insulin resistance, but your pancreas can increase insulin production to keep your blood sugar levels in range, you won’t have any symptoms^[1].

But over time, the condition can get worse, and the cells in your pancreas that make insulin can wear out. Eventually, your pancreas can’t produce enough insulin to overcome it, leading to elevated blood sugar^[1]. People with consistently high blood sugar levels can experience the following symptoms^[1]:

• Unexplained weight loss
• Fatigue
• Increased thirst
• Frequent urination
• Increased hunger
• Blurred vision
• Yeast infections

Many people have no symptoms of prediabetes, often for years. Prediabetes may be invisible until it develops into Type 2 diabetes^[1]. Some people with prediabetes may experience darkened skin in their armpit or back and sides of their neck, called acanthosis nigricans, skin tags, or eye changes that can lead to diabetes-related retinopathy^[1].

If you’re experiencing any of these symptoms, it’s important to see your healthcare provider^[1].

What causes insulin resistance?

Scientists still have a lot to discover about how exactly insulin resistance develops. So far, they’ve identified several genes that make a person more or less likely to develop insulin resistance^[1]. Providers also know that gaining weight can worsen it, and losing weight can help improve it^[1].

Insulin resistance is primarily an acquired condition related to excess body fat, though genetic causes are also identified^[6]. When your body is exposed to too much blood sugar over an extended period of time, you can develop insulin resistance^[5].

Here’s what happens: A lot of blood sugar enters your bloodstream. Your pancreas pumps out high levels of insulin to get more blood sugar into your cells. Over time, your cells stop responding well to insulin. Your blood sugar remains high, which causes your pancreas to keep releasing more insulin to make your cells respond^[5]. Eventually, your pancreas can’t keep up and your blood sugar keeps increasing^[5].

High blood sugar is damaging to the body, so your body keeps trying to remove excess blood sugars. It stores extra sugar in your liver and muscles. When they’re full, the liver sends the remaining sugar to be stored as body fat, causing weight gain^[5].

Certain medications can also cause insulin resistance, including glucocorticoids, certain antipsychotics, and HIV medications^[2]. Using steroid medication for a brief period can cause temporary insulin resistance^[1].

Related health conditions

Insulin resistance is associated with several serious health conditions^[1]:

• Obesity
• Cardiovascular disease
• Metabolic dysfunction-associated steatotic liver disease
• Metabolic syndrome
• Polycystic ovary syndrome (PCOS)

The metabolic consequences of insulin resistance can result in hyperglycemia, hypertension, dyslipidemia, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, and a prothrombotic state^[6].

The predominant consequence of insulin resistance is Type 2 diabetes. Insulin resistance is thought to precede the development of Type 2 diabetes by 10 to 15 years^[6]. Insulin resistance sets the stage for prediabetes and Type 2 diabetes^[5].

In 2021, about 97.6 million people in the United States ages 18 and older had prediabetes^[3]. People with prediabetes may be more at risk for developing Type 2 diabetes, but not everyone with prediabetes develops Type 2 diabetes^[3].

One half of patients with essential hypertension are insulin resistant^[7]. The lipid profile of patients with Type 2 diabetes includes decreased high-density lipoprotein cholesterol levels, increased serum very-low-density lipoprotein cholesterol and triglyceride levels^[7].

How is it diagnosed?

In clinical practice, no single laboratory test is used to diagnose insulin resistance syndrome. Diagnosis is based on clinical findings corroborated with laboratory tests^[9]. The clinical definition of insulin resistance remains elusive, as there is no generally accepted test for insulin resistance^[6].

Individual patients are screened based on the presence of comorbid conditions. Laboratory tests include the plasma glucose level, the fasting insulin level, and a lipid profile, among others^[9].

You can’t tell if someone has insulin resistance by looking at them. Although overweight and obesity are risk factors, you do not have to have them to have insulin resistance^[5]. Other signs that suggest insulin resistance include high blood sugar levels, high triglycerides, high LDL (bad) cholesterol, low HDL (good) cholesterol, family history of Type 2 diabetes, and physical inactivity^[5].

Treatment and management

Lifestyle modifications should be the primary focus when treating insulin resistance^[6]. Treatment involves pharmacologic therapy to reduce insulin resistance, along with surgical management of underlying causes if appropriate^[9].

Modifications of diet and activity are recommended. Nutritional intervention with calorie reduction and avoidance of carbohydrates that stimulate excessive insulin demand is a cornerstone of treatment^[6]. Physical activity helps to increase energy expenditure and improve skeletal muscle insulin sensitivity^[6].

Present treatment consists of sensible lifestyle changes, including weight loss to attain healthy body weight, 30 minutes of accumulated moderate-intensity physical activity per day and increased dietary fiber intake^[7]. Weight reduction improves insulin sensitivity in cases of obesity and in most of the obesity-related insulin-resistant states. Restriction of caloric intake is indicated^[13].

Medications also can improve insulin response and reduce insulin demand^[6]. Medications that reduce insulin resistance include metformin, the thiazolidinediones, sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists^[9].

Metformin is a biguanide; it reduces hepatic glucose output and increases the uptake in the peripheral tissues. Metformin is a major drug in the treatment of patients who are obese and have Type 2 diabetes. The drug enhances weight reduction and improves lipid profile and vascular integrity^[13].

Pharmacotherapy is not currently recommended for patients with isolated insulin resistance^[7]. Comorbid conditions should be evaluated and addressed; this is generally feasible on an outpatient basis, though some patients will require admission^[9].

Prevention and reversal

The good news is that many people can take steps to prevent or delay prediabetes and Type 2 diabetes^[3]. Even if the genetic chips and other factors are stacked against you, there are plenty of steps you can take^[12].

If you’re overweight, even modest weight loss can boost insulin response. Some people recommend a specific diet or time-restricted eating, but as long as you reduce the total number of calories you eat, weight loss and improved insulin sensitivity should follow^[12].

Regular physical activity, such as exercising, helps move sugar into the muscles for storage. Working out for half an hour 3–5 days per week can help promote an immediate increase in insulin sensitivity^[25]. Exercise improves insulin sensitivity by increasing oxidative enzymes, increasing GLUT-4, increasing capillarity, and reducing central adiposity^[13].

When choosing foods, there are key factors you want to keep in mind: fiber, healthy fats, lean proteins and carbohydrates. These foods can help prevent the accumulation of excess sugar as fat, which can, in turn, improve your insulin sensitivity^[23]. Foods high in fiber promote a feeling of fullness, which can prevent overeating. Replacing refined grains with fiber-rich foods like whole grains, fruits, vegetables and reducing sugary drinks can both help promote proper insulin resistance^[23].

Getting enough sleep can help improve insulin sensitivity. Catching up on lost sleep may help improve the effects of less sleep on insulin resistance^[25]. Stress encourages the body to go into “fight-or-flight” mode, which stimulates the production of stress hormones that break down glycogen. Ongoing stress keeps your stress hormone levels high, stimulating nutrient breakdown and increasing blood sugar^[25].

Dietary indiscretion, such as consumption of a diet high in cholesterol and sodium, should be avoided. Alcohol use should be limited. Smoking cessation is indicated. Patients should avoid physical inactivity^[13].

Being an active participant in your own health and taking proactive steps to control blood sugar levels can help prevent insulin resistance and improve your long-term health and wellbeing^[22].