Insulin resistance (IR) is a prevalent metabolic condition affecting approximately 40% of American adults aged 18 to 44 who do not have diabetes.

Over time, IR can contribute to the development of type 2 diabetes (T2D), often preceding its onset by 10 to 15 years. Beyond T2D, IR is linked to various health issues, including obesity, cardiovascular disease, polycystic ovary syndrome (PCOS), nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome.

These conditions collectively strain the healthcare system due to treatment costs and societal implications, emphasizing the importance of early detection and intervention.

In this article, we’ll explore insulin resistance, its role in weight gain, underlying causes, symptoms, diagnostic tests, and management strategies. Gain insight into the complexities of this condition to understand its impact on health and how to address it effectively.

Key Findings

  • Insulin resistance can lead to the development of type 2 diabetes and is linked to various health issues, including obesity, cardiovascular disease, PCOS, NAFLD, and metabolic syndrome.
  • There is a bidirectional relationship between insulin resistance and weight gain, with each contributing to the other’s development.
  • Obesity, aging, physical inactivity, poor diet, certain medications, hormonal disorders, and genetic conditions can contribute to insulin resistance.
  • Diagnosing insulin resistance involves comprehensive evaluation, including medical history, physical examination, and various tests such as fasting insulin levels and glucose/insulin ratio.
  • Lifestyle modifications such as adopting a healthy diet, regular exercise, and weight management are essential for managing insulin resistance.

Understanding Insulin Resistance

What is insulin?

Insulin is a hormone produced by the beta (?) cells, a specialized cell located in the islets of Langerhans within the pancreas. Insulin regulates the metabolism of various nutrients, including carbohydrates, proteins, and fats.

When you eat, especially foods rich in carbohydrates, your blood sugar level rises. In response to this increase, insulin is released into the bloodstream.

Insulin stimulates glucose absorption from the bloodstream into different types of cells, such as fat cells, skeletal muscle cells, and liver cells. Once inside the cells, glucose can be used as an immediate energy source or stored for later use.

What is insulin resistance?

Insulin resistance occurs when the cells become less responsive to insulin signals. As a result, they don’t absorb glucose properly, leading to elevated blood sugar levels. To compensate for this, the pancreas increases its insulin production, leading to even higher insulin levels in the bloodstream.

Insulin Resistance and Weight Gain

Can insulin resistance cause weight gain?

Insulin resistance and weight gain can influence each other in a bidirectional manner, meaning they can both contribute to each other’s development. Simply put, gaining weight can increase insulin resistance, and being more insulin-resistant can lead to further weight gain.

Here’s how each factor can influence the other:

Insulin Resistance Leading to Weight Gain

All tissues in the body that have insulin receptors can potentially become insulin resistant. However, the three primary sites where insulin resistance manifests and causes weight gain include:

  • Skeletal muscle: Up to 70% of glucose disposal occurs in skeletal muscle, making it a major glucose disposal site. When skeletal muscle becomes insulin-resistant, its ability to absorb glucose decreases. As a result, glucose is diverted away from muscle tissue and directed towards the liver.
  • Liver: The liver breaks down and converts substances into forms that our body can use for fuel. In the liver, extra glucose is used to make new fats through a process called de novo lipogenesis (DNL). More glucose reaching the liver means more fat production through DNL.
  • Adipose tissue: The fats produced by DNL are released into the bloodstream in the form of triglycerides. Elevated triglyceride levels result in increased fat storage in the body, leading to the accumulation of adipose tissue (body fat). Consequently, this contributes to higher body weight, waist circumference, and body mass index.

The buildup of fat in these tissues worsens insulin resistance throughout the body. This sets off a vicious cycle where insulin resistance in one tissue worsens insulin resistance in another.

Weight Gain Contributing to Insulin Resistance

Experts believe that obesity, particularly excessive fat around the abdomen and organs (known as visceral fat), is a primary cause of insulin resistance. A waist measurement of 40 inches or more for men and 35 inches or more for women is associated with insulin resistance, even if the body mass index (BMI) falls within the normal range.

While fat tissue was previously thought to only store energy, studies have revealed that belly fat produces hormones and substances that can contribute to chronic inflammation in the body. This inflammation may play a role in insulin resistance, type 2 diabetes, and cardiovascular disease.

While both factors can influence each other, the exact relationship between insulin resistance and weight gain may vary among individuals and can be influenced by several factors.

Causes of Insulin Resistance

Person standing on weight scale

Understanding the possible causes of insulin resistance is important for developing effective prevention and management strategies.

Contributing Factors to Acquired Insulin Resistance

Obesity

For years, it has been widely acknowledged that there’s a connection between obesity and insulin resistance. However, the exact mechanisms and sequence of events triggering insulin resistance are still unclear.

Numerous studies have proposed various mechanisms that might contribute to insulin resistance in obesity.

  • Endoplasmic Reticulum (ER) Stress: Recent experiments conducted in mouse models suggest a connection between ER stress and insulin resistance in tissues such as the liver, adipose tissue, and skeletal muscle. One study demonstrated that obesity induces ER stress in the liver, which impairs insulin signaling pathways.
  • Adipose Tissue Hypoxia: Studies suggest that as adipose tissue (fat tissue) expands due to obesity, hypoxia (low oxygen levels) develops within the tissue. Prolonged hypoxia disrupts insulin signaling in the tissue, potentially causing insulin resistance.
  • Oxidative Stress: Obesity can lead to increased production of reactive oxygen species (ROS). This leads to a condition known as oxidative stress. In small amounts, ROS play a role in cell signaling, but when there’s an excess, they can cause damage to cells. Recent research suggests that this damage is directly linked to the development and progression of various chronic diseases, including insulin resistance.

Aging

Aging poses an inevitable risk factor for insulin resistance due to a variety of factors, including:

  • Declining Glucose Effectiveness: Factors such as decreased physical activity, medication use, existing health conditions, and alterations in insulin secretion likely contribute to this decline.
  • Reduced Insulin Secretion: Aging often results in decreased insulin production due to the decline in the sensitivity of beta cells, which are responsible for producing insulin. This decline in beta-cell sensitivity can impair the body’s ability to regulate blood sugar levels efficiently.
  • Age-Related Skeletal Muscle Issues: As mentioned above, skeletal muscle is the body’s primary site for glucose disposal. As age increases, skeletal muscle undergoes various changes and dysfunctions, such as decreased muscle mass, that can heighten the risk of insulin resistance.

Physical Inactivity

Physical inactivity significantly contributes to the development of insulin resistance through various physiological mechanisms.

A study found that sedentary individuals have lower insulin sensitivity. Additionally, their pancreatic beta cells may not respond as effectively when carbohydrates are consumed, leading to difficulties in regulating blood sugar levels after meals.

In contrast, individuals who started being more physically active experienced improvements in insulin sensitivity.

Diet

Consuming more calories than the body requires, especially from unhealthy sources like refined carbohydrates and sugary foods, can result in weight gain and obesity. Excess body fat, especially visceral fat, is closely linked to insulin resistance.

High intake of sugary foods and beverages can cause blood sugar levels to spike, prompting the pancreas to release more insulin to regulate glucose levels.

Furthermore, diets rich in saturated and trans fats can accumulate in cells, particularly in muscles and the liver, disrupting insulin signaling pathways and reducing insulin sensitivity.

Did you Know

Historically, doctors recommended limiting caffeine consumption for patients due to studies indicating that caffeine could temporarily raise blood pressure and decrease insulin sensitivity.

However, newer research has revealed a more nuanced understanding. Studies now show that while acute (short-term) consumption of caffeine can lead to a temporary increase in blood pressure and reduced insulin sensitivity, chronic (long-term) consumption of coffee or caffeine is associated with improved insulin sensitivity and glucose metabolism.

Additionally, long-term coffee or caffeine intake has been linked to a lower risk of developing type 2 diabetes.

Medications

Several drugs can worsen insulin resistance or interfere with glucose metabolism. Some examples include:

  • Thiazides – Hydrochlorothiazide (HCTZ), Chlorthalidone, and Indapamide
  • Beta-blockers – Metoprolol, Propranolol, and Atenolol
  • Second-generation antipsychotics, also known as atypical antipsychotics – Abilify, Geodon, Seroquel, and Zyprexa
  • Fluoroquinolones – Levaquin and Cipro
  • Corticosteroids – Prednisone, Methylprednisolone, and Prednisolone
  • Niacin

Hormonal Disorders Linked to Insulin Resistance

Some medical conditions involve abnormalities in the endocrine system, responsible for producing and regulating hormones in the body. Certain hormones may counteract the effects of insulin. Elevated levels of these hormones or heightened actions due to abnormalities can interfere with insulin’s ability to regulate blood sugar effectively.

Examples of hormonal disorders known to cause insulin resistance include:

  • Acromegaly: A condition where the body makes too much growth hormone (GH) for a long time. This extra growth hormone can cause problems like insulin resistance. Over time, this can lead to glucose intolerance, and eventually, it can lead to diabetes.
  • Hyperprolactinaemia: Refers to elevated levels of the hormone prolactin in the bloodstream. It’s the most common dysfunction of the hypothalamic-pituitary axis and occurs more frequently in women. Scientific studies have found a connection between insulin resistance and hyperprolactinaemia, indicating that higher levels of prolactin are often associated with increased resistance of body tissues to insulin.
  • Hyperthyroidism:  A condition characterized by the thyroid gland producing an excessive amount of thyroid hormone. This condition leads to an increase in inflammation markers in the body, which are also associated with insulin resistance in tissues outside of major organs such as the liver and muscles.
  • Hypothyroidism: Occurs when the thyroid gland doesn’t produce enough thyroid hormone. Researchers have found that both overt (clearly symptomatic) and subclinical (not showing clear symptoms) hypothyroidism result in tissues being less sensitive to insulin.
  • Cushing’s Syndrome: When there is an excessive amount of cortisol, the body’s main stress hormone, a condition known as hypercortisolism or Cushing’s syndrome may occur. High levels of cortisol in the blood can lead to metabolic disturbances and the development of insulin resistance.

Genetic Conditions Leading to Insulin Resistance

Various genetic disorders can lead to significant resistance to insulin. The most common syndromes are collectively referred to as inherited severe insulin resistance syndromes, resulting from mutations in the INSR gene.

Mutations in the INSR gene result in the production of faulty insulin receptors, which cannot properly transmit signals from insulin. These genetic conditions include:

  • Type A insulin resistance syndrome: Considered to be at the milder end of the spectrum. Its features typically don’t become apparent until puberty or later, and it’s generally not life-threatening. It’s estimated that this condition affects approximately 1 in 100,000 people worldwide.
  • Rabson-Mendenhall syndrome: This syndrome falls between Donohue syndrome and type A insulin resistance syndrome. Symptoms appear early and affected individuals typically live into their teens or twenties. Death usually occurs due to complications of diabetes, such as diabetic ketoacidosis. This condition affects fewer than 1 per million people worldwide.
  • Donohue syndrome:  The most severe form of inherited severe insulin resistance syndromes, with most affected children not surviving beyond age 2. It is estimated to affect fewer than 1 per million people worldwide.

Other genetic disorders leading to insulin resistance include:

  • Type B insulin resistance syndrome: Also known as atypical autoimmune insulin resistance syndrome or autoantibody-mediated insulin resistance syndrome. This condition is associated with the presence of autoantibodies that target the insulin receptor, leading to impaired insulin signaling and resistance to the effects of insulin in the body’s tissues.
  • Lipodystrophies: These are diverse rare disorders, with an estimated occurrence of 1.3–4.7 cases per million and even fewer for genetic lipodystrophies. In these conditions, the body either lacks or has an abnormal distribution of fat tissue. This can lead to metabolic complications such as insulin resistance, diabetes mellitus, and dyslipidemia.

Signs and Symptoms of Insulin Resistance

Close-up image of trainer measuring waist of her slim fit client before workout

Insulin resistance often doesn’t present noticeable symptoms, and it’s typically detected during routine medical check-ups or through blood tests. Healthcare providers may observe the following indicators to identify insulin resistance in individuals:

  • Heightened thirst
  • Frequent need to urinate
  • Heightened appetite
  • Blurred eyesight
  • Headaches
  • Infections in the vaginal and skin areas
  • Delays in the healing process for cuts and sores
  • Abdominal obesity, typically defined as a waistline exceeding 40 inches in men and 35 inches in women.
  • Skin tags or patches of dark, velvety skin known as acanthosis nigricans.
  • Elevated blood pressure, with readings of 130 over 80 or higher.
  • Fasting glucose levels equal to or exceeding 100 milligrams per deciliter, or blood sugar levels equal to or exceeding 140 milligrams per deciliter two hours after a glucose load test.
  • An A1C level falling between 5.7% and 6.3%.
  • Elevated fasting triglyceride levels, exceeding 150 milligrams per deciliter.
  • Low HDL cholesterol levels, under 40 milligrams per deciliter in men and under 50 milligrams per deciliter in women.

Diagnosis and Tests of Insulin Resistance

Insulin resistance poses a diagnostic challenge because routine testing is not widely available. Often, individuals with insulin resistance may not experience symptoms.

Diagnosing insulin resistance involves a comprehensive evaluation by healthcare providers, taking into account various factors, such as:

  • Medical history
  • Family history
  • Physical examination
  • Test results

Several tests are available to aid in diagnosing insulin resistance:

  • Hyperinsulinemic-Euglycemic Glucose Clamp Technique: This technique is considered the gold standard for measuring insulin resistance. It involves administering insulin through an IV while maintaining a steady glucose level. However, it’s complex and not practical for routine use.
  • Insulin Sensitivity Test (IST) and Insulin Tolerance Test (ITT): These variations of the glucose clamp technique assess insulin sensitivity but are also less commonly used due to their complexity.
  • Fasting Insulin (I0): This test measures fasting serum insulin levels and is relatively inexpensive.
  • Glucose/Insulin Ratio (G/I Ratio): The G/I ratio is a widely used index of insulin sensitivity, particularly in women with PCOS. It involves calculating the ratio of glucose to insulin levels, with lower values indicating higher degrees of insulin resistance.
  • Homeostatic Model Assessment (HOMA): HOMA is a commonly utilized method in clinical research to evaluate insulin sensitivity. Instead of relying solely on fasting insulin or G/I ratio, HOMA calculates insulin sensitivity by multiplying fasting glucose by fasting insulin and dividing the product by a constant.

Management and Treatment of Insulin Resistance

Managing insulin resistance requires a comprehensive approach. While genetics play a role, lifestyle factors like poor diet, lack of exercise, and obesity also contribute to insulin resistance. Making small changes in these areas can result in significant improvements in health over time.

Lifestyle Modifications

One of the most effective ways to manage insulin resistance is through lifestyle changes. This includes:

  • Healthy Diet: Focus on consuming a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Limit intake of refined carbohydrates, sugary foods, and saturated fats, which can worsen insulin resistance.
  • Regular Exercise: Physical activity helps improve insulin sensitivity and glucose metabolism. Aim for at least 30 minutes of moderate-intensity exercise most days of the week, such as brisk walking, cycling, or swimming.
  • Weight Management: Achieving and maintaining a healthy weight can significantly reduce insulin resistance. Even modest weight loss can improve insulin sensitivity and lower blood sugar levels.

Medications and Supplements

Currently, there are no medications specifically approved to treat insulin resistance. However, in some cases, healthcare providers may prescribe diabetes medications to help manage insulin resistance and associated conditions.

These medications may include:

  • Metformin: A commonly prescribed medication for type 2 diabetes, metformin can also improve insulin sensitivity in individuals with insulin resistance.
  • Insulin Sensitizers: Certain medications, such as thiazolidinediones (TZDs), can improve insulin sensitivity and glucose uptake in cells.
  • Supplements: Some supplements, such as omega-3 fatty acids and chromium, have been studied for their potential benefits in improving insulin sensitivity.

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Monitoring and Regular Check-Ups

Regularly checking your blood sugar levels and keeping an eye on other important health markers is important for managing insulin resistance. Your healthcare provider might suggest:

  • Blood Tests: Regular blood tests, including fasting glucose, A1c, and lipid panels, can help track changes in blood sugar levels and lipid profiles.
  • Health Screenings: Regular health screenings for conditions associated with insulin resistance, such as cardiovascular disease and fatty liver disease, are important for early detection and intervention.

Takeaway

Insulin resistance is a complex metabolic condition that occurs when cells in the body become less responsive to the effects of insulin.

Several factors contribute to the development of insulin resistance, including genetics, lifestyle factors, obesity, inflammation, and certain medical conditions. However, the precise mechanisms underlying insulin resistance are not fully understood.

Management and prevention of insulin resistance involve lifestyle modifications such as maintaining a healthy diet, regular physical activity, and weight management. In some cases, medications such as insulin-sensitizing drugs or medications to control blood sugar levels may be prescribed to manage insulin resistance.

Frequently Asked Questions

What causes insulin resistance in PCOS?

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects reproductive-aged women. Its exact cause is not fully understood, but several factors contribute to its development, including genetic predisposition, hormonal imbalances, hyperinsulinemia, obesity, lifestyle factors, and environmental influences.

Can insulin resistance be tested at home?

No. At-home tests for insulin resistance are unavailable. However, you can still assess your risk using indirect measures and various risk factors. These include measuring your waist circumference, calculating your BMI, considering your family history of type 2 diabetes or insulin resistance, evaluating your lifestyle habits like diet and exercise, and reviewing your medical history, especially if you’ve been diagnosed with conditions linked to insulin resistance such as PCOS or gestational diabetes.

Is insulin resistance reversible?

Yes, insulin resistance is often reversible, especially if addressed early and through lifestyle modifications. Key strategies for enhancing insulin sensitivity and potentially reversing insulin resistance involve adopting a balanced diet, regular physical activity, maintaining a healthy weight, stress reduction, ensuring adequate sleep, moderating alcohol intake, and avoiding smoking. However, the effectiveness of these approaches can differ based on individual factors like genetics, the degree of insulin resistance, and concurrent health conditions.

Can insulin resistance be prevented or delayed?

Yes, adopting a healthy diet and increasing physical activity levels can effectively prevent or delay the onset of insulin resistance. Focus on consuming a diet abundant in whole foods such as fruits, vegetables, whole grains, lean proteins, and healthy fats. Reducing intake of refined carbohydrates, sugars, and processed foods can help prevent insulin resistance. Additionally, minimizing sedentary behavior and integrating more movement into daily routines, even through small changes like opting for stairs instead of elevators or taking short walks, can notably enhance insulin sensitivity.

Can losing weight help with insulin resistance?

Yes, research indicates that weight loss, achieved through caloric restriction and exercise, improves insulin sensitivity. Excess weight, particularly abdominal fat, is strongly associated with insulin resistance. Losing weight, especially if you reduce visceral fat (fat stored around the organs), can improve insulin sensitivity.

Are there certain exercises that help with insulin resistance?

Combining aerobic and resistance exercise has the most pronounced effect on improving insulin sensitivity compared to performing either type of exercise alone. Aerobic exercise directly enhances insulin sensitivity, while resistance training increases muscle mass, which in turn positively impacts glucose uptake.

What food should I eat to fight insulin resistance?

Focus on a balanced diet, limit sugar and refined carbs since insulin resistance often involves difficulty processing sugars and carbohydrates. Include protein with each meal as it helps to stabilize blood sugar levels and promotes satiety, which can help you feel full and satisfied for longer periods. Include sources of lean protein such as chicken, fish, tofu, beans, and lentils in your meals.

Can you be insulin-resistant without being diabetic?

Yes. Insulin resistance is a condition that can impact anyone, regardless of whether they have diabetes, and it may manifest as either a temporary or chronic issue.

How common is insulin resistance?

Insulin resistance is considerably common and affects a significant portion of adults globally, with rates ranging from 15.5% to 46.5% in 2020. However, many individuals remain unaware of their condition because there aren’t standardized tests for detecting insulin resistance, and symptoms typically only appear when it advances to prediabetes or Type 2 diabetes.

What is your insulin level if you are insulin-resistant?

The World Health Organization (WHO) Consensus Group suggests that individuals falling within the lowest 25% of the general population in terms of insulin sensitivity index (ISI) can be considered insulin resistant. While the European Group for the Study of Insulin Resistance adopted a more stringent criterion, defining insulin resistance as ISI falling within the lowest 10% of a specific subgroup – non-obese, nondiabetic, normotensive Caucasians.

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