Insulin Resistance & Prediabetes

We have selected the following expert medical opinion based on its clarity, reliability and accuracy. Credit: Source: National Institute of Diabetes and Digestive and Kidney Diseases (see below), edited by D George A. Bray and Dr Richard F. Hamman. Please refer to your own medical practitioner for a final perspective, assessment or evaluation. 

Overview

What is insulin?

Insulin is a hormone made in the pancreas, an organ located behind the stomach. The pancreas contains clusters of cells called “islets”. Beta cells within the islets make insulin and release it into the blood.

Insulin plays a major role in metabolism—the way the body uses digested food for energy. The digestive tract breaks down carbohydrates—sugars and starches found in many foods—into glucose. Glucose is a form of sugar that enters the bloodstream. With the help of insulin, cells throughout the body absorb glucose and use it for energy.

Insulin's Role in Blood Glucose Control

When blood glucose levels rise after a meal, the pancreas releases insulin into the blood. Insulin and glucose then travel in the blood to cells throughout the body.

Insulin:

• helps muscle, fat, and liver cells absorb glucose from the bloodstream, lowering blood glucose levels.
• stimulates the liver and muscle tissue to store excess glucose. The stored form of glucose is called glycogen.
• lowers blood glucose levels by reducing glucose production in the liver.

In a healthy person, these functions allow blood glucose and insulin levels to remain in the normal range.

What happens with insulin resistance?

In insulin resistance, muscle, fat, and liver cells do not respond properly to insulin and thus cannot easily absorb glucose from the bloodstream. As a result, the body needs higher levels of insulin to help glucose enter cells.

The beta cells in the pancreas try to keep up with this increased demand for insulin by producing more. As long as the beta cells are able to produce enough insulin to overcome the insulin resistance, blood glucose levels stay in the healthy range.

Over time, insulin resistance can lead to type 2 diabetes and prediabetes because the beta cells fail to keep up with the body's increased need for insulin. Without enough insulin, excess glucose builds up in the bloodstream, leading to diabetes, prediabetes, and other serious health disorders.

Causes

What causes insulin resistance?

Although the exact causes of insulin resistance are not completely understood, scientists think the major contributors to insulin resistance are excess weight and physical inactivity.

1. Excess Weight:

Some experts believe obesity, especially excess fat around the waist, is a primary cause of insulin resistance. Scientists used to think that fat tissue functioned solely as energy storage. However, studies have shown that belly fat produces hormones and other substances that can cause serious health problems such as insulin resistance, high blood pressure, imbalanced cholesterol, and cardiovascular disease (CVD).

Belly fat plays a part in developing chronic, or long-lasting, inflammation in the body. Chronic inflammation can damage the body over time, without any signs or symptoms. Scientists have found that complex interactions in fat tissue draw immune cells to the area and trigger low-level chronic inflammation. This inflammation can contribute to the development of insulin resistance, type 2 diabetes, and CVD. Studies show that losing the weight can reduce insulin resistance and prevent or delay type 2 diabetes.

2. Physical Inactivity

Many studies have shown that physical inactivity is associated with insulin resistance, often leading to type 2 diabetes. In the body, more glucose is used by muscle than other tissues. Normally, active muscles burn their stored glucose for energy and refill their reserves with glucose taken from the bloodstream, keeping blood glucose levels in balance.

Studies show that after exercising, muscles become more sensitive to insulin, reversing insulin resistance and lowering blood glucose levels. Exercise also helps muscles absorb more glucose without the need for insulin. The more muscle a body has, the more glucose it can burn to control blood glucose levels.

3. Other Causes

Other causes of insulin resistance may include ethnicity; certain diseases; hormones; steroid use; some medications; older age; sleep problems, especially sleep apnoea; and cigarette smoking.
 

Does sleep matter?

Yes. Studies show that untreated sleep problems, especially sleep apnoea, can increase the risk of obesity, insulin resistance, and type 2 diabetes. Night shift workers may also be at increased risk for these problems. Sleep apnoea is a common disorder in which a person's breathing is interrupted during sleep. People may often move out of deep sleep and into light sleep when their breathing pauses or becomes shallow. This results in poor sleep quality that causes problem sleepiness, or excessive tiredness, during the day.

Many people aren't aware of their symptoms and aren't diagnosed. People who think they might have sleep problems should talk with their health care provider.
 

What is Prediabetes?

Prediabetes is a condition in which blood glucose or HbA1c (A1C) levels—which reflect average blood glucose levels—are higher than normal but not high enough for a diagnosis of diabetes. Prediabetes is becoming more common in the United States and many parts of the World. The U.S. Department of Health and Human Services estimates that at least 84.1 million U.S. adults ages 18 or older had prediabetes in 2015. People with prediabetes are at increased risk of developing type 2 diabetes and CVD, which can lead to heart attack or stroke.

How does insulin resistance relate to type 2 diabetes and prediabetes?

Insulin resistance increases the risk of developing type 2 diabetes and prediabetes. Prediabetes usually occurs in people who already have insulin resistance. Although insulin resistance alone does not cause type 2 diabetes, it often sets the stage for the disease by placing a high demand on the insulin-producing beta cells. In prediabetes, the beta cells can no longer produce enough insulin to overcome insulin resistance, causing blood glucose levels to rise above the normal range.

Once a person has prediabetes, continued loss of beta cell function usually leads to type 2 diabetes. People with type 2 diabetes have high blood glucose. Over time, high blood glucose damages nerves and blood vessels, leading to complications such as heart disease, stroke, blindness, kidney failure, and lower-limb amputations.

Studies have shown that most people with prediabetes develop type 2 diabetes within 10 years, unless they change their lifestyle. Lifestyle changes include losing 5 to 7 percent of their body weight by making changes in their diet and level of physical activity.

Symptoms

What are the symptoms of insulin resistance and prediabetes?

Insulin resistance and prediabetes usually have no symptoms. People may have one or both conditions for several years without knowing they have them. Even without symptoms, health care providers can identify people at high risk by their physical characteristics, also known as risk factors.

Individuals with a severe form of insulin resistance may have dark patches of skin, usually on the back of the neck. Sometimes people have a dark ring around their neck. Dark patches may also appear on elbows, knees, knuckles, and armpits. This condition is called acanthosis nigricans.

Testing

Who should be tested for prediabetes?

The American Diabetes Association (ADA) recommends that testing to detect prediabetes be considered in adults who are overweight or obese and have one or more additional risk factors for diabetes. (See "Body Mass Index (BMI)" below). However, not everyone who is overweight will get type 2 diabetes. People without these risk factors should begin testing at age 45.
 

Risk factors for prediabetes—in addition to being overweight or obese or being age 45 or older—include the following:

• Being physically inactive
• Having a parent or sibling with diabetes
• Having a family background that is African American, Alaska native, American Indian, Asian American, Hispanic/Latino, or Pacific Islander American
• Giving birth to a baby weighing more than 4 kg (9 pounds)
• Being diagnosed with gestational diabetes—diabetes that develops only during pregnancy
• Having high blood pressure—140/90 mmHg or above—or being treated for high blood pressure
• HDL cholesterol level below the average (check your blood test’s reference values)
• A triglyceride level above the average (check your blood test’s reference values)
• Having polycystic ovary syndrome (PCOS)
• Having prediabetes, impaired fasting glucose (IFG), or impaired glucose tolerance (IGT) on an earlier testing
• Having other conditions associated with insulin resistance, such as obesity or acanthosis nigricans
• Having cardio vascular disease (CVD)

If test results are normal, testing should be repeated at least every 3 years. Testing is important for early diagnosis. Catching prediabetes early gives people time to change their lifestyle and prevent type 2 diabetes and CVD. Health care providers may recommend more frequent testing depending on initial results and risk status.

In addition to weight, the location of excess fat on the body can be important. A waist measurement of 94 – 102 cm or more for men and 80 – 88 cm or more for women is linked to insulin resistance and increases a person's risk for type 2 diabetes. This is true even if a person's BMI falls within the normal range.
 

How to Measure the Waist

To measure the waist, a person should:

• Place a tape measure around the bare abdomen just above the hip bone
• Make sure the tape is snug but isn't digging into the skin and is parallel to the floor
• Relax, exhale, and measure

Source: Adapted from www.cdc.gov 

If you are overweight or obese, choose sensible ways to get in shape:

• Avoid crash diets: Instead, eat less of the foods you usually have. Limit the amount of fat you eat.
• Increase your physical activity: Aim for at least 30 minutes of physical activity most days of the week.

Set a reasonable weight-loss goal, such as losing 0.5 kg a week. Aim for a long-term goal of losing 5 to 7 percent of your total body weight. To estimate this amount in pounds, find the weight closest to yours on the chart below. Follow the row across to see how many pounds you need to lose.

What is metabolic syndrome?

Metabolic syndrome, also called insulin resistance syndrome, is a group of traits and medical conditions linked to overweight and obesity that puts people at risk for both CVD and type 2 diabetes.

Metabolic syndrome is defined as the presence of any three of the following:

• Large waist size: waist measurement of 94-102 cm or more for men and 80-88 cm or more for women
• High triglycerides in the blood: triglyceride level of 1.7 mmol/L of blood or above, or taking medication for elevated triglyceride level
• Abnormal levels of cholesterol in the blood: HDL, or good, cholesterol level below 1.0 mmol/L for men and below 1.28 mmol/L for women, or taking medication for low HDL
• High blood pressure: blood pressure level of 130/85 or above, or taking medication for elevated blood pressure
• Higher than normal blood glucose levels: fasting blood glucose level of 100 mg/dL or above, or taking medication for elevated blood glucose

In addition to type 2 diabetes, metabolic syndrome has been linked to the following health disorders:

• obesity
• CVD
• PCOS
• non-alcoholic fatty liver disease
• chronic kidney disease

However, not everyone with these disorders has insulin resistance, and some people may have insulin resistance without getting these disorders.

People who are obese or who have metabolic syndrome, insulin resistance, type 2 diabetes, or prediabetes often also have low-level inflammation throughout the body and blood clotting defects that increase the risk of developing blood clots in the arteries. These conditions contribute to increased risk for CVD.

Diagnosis 

How are insulin resistance and prediabetes diagnosed?

Health care providers use blood tests to determine whether a person has prediabetes, but they do not usually test specifically for insulin resistance. Insulin resistance can be assessed by measuring the level of insulin in the blood.

However, the test that most accurately measures insulin resistance, called the euglycemic clamp, is too costly and complicated to be used in most health care providers' offices. The clamp is a research tool used by scientists to learn more about glucose metabolism. Research has shown that if blood tests indicate prediabetes, insulin resistance most likely is present.

Blood Tests for Prediabetes

All blood tests involve drawing blood at a health care provider's office or commercial facility and sending the sample to a lab for analysis. Lab analysis of blood is needed to ensure test results are accurate. Glucose measuring devices used in a health care provider's office, such as finger-stick devices, are not accurate enough for diagnosis but may be used as a quick indicator of high blood glucose.

Prediabetes can be detected with one of the following blood tests:

• the HbA1c test
• the fasting plasma glucose (FPG) test
• the oral glucose tolerance test (OGTT)

HbA1c test. Sometimes called haemoglobin HbA1c, or glycohemoglobin test, this test reflects average blood glucose levels over the past 3 months. This test is the most reliable test for prediabetes, but it is not as sensitive as the other tests. In some individuals, it may miss prediabetes that could be caught by glucose tests.

Although some health care providers can quickly measure HbA1c in their office, that type of measurement—called a point-of-care test—is not considered reliable for diagnosis. For diagnosis of prediabetes, the HbA1c test should be analysed in a laboratory using a method that is certified by the NGSP.

The HbA1c test can be unreliable for diagnosing prediabetes in people with certain conditions that are known to interfere with the results. Interference should be suspected when HbA1c results seem very different from the results of a blood glucose test. People of African, Mediterranean, or Southeast Asian descent, or people with family members with sickle cell anaemia or a thalassemia, are particularly at risk of interference. People in these groups may have a less common type of haemoglobin, known as a haemoglobin variant, that can interfere with some HbA1c tests.

An HbA1c of 5.7 to 6.4 percent indicates prediabetes.

Fasting plasma glucose test:  This test measures blood glucose in people who have not eaten anything for at least 8 hours. This test is most reliable when done in the morning. Prediabetes found with this test is called IFG.

Fasting glucose levels of 5.6 mmol/l to 7.0 mmol/l indicate prediabetes.

OGTT: This test measures blood glucose after people have not eaten for at least 8 hours and 2 hours after they drink a sweet liquid provided by a health care provider or laboratory. Prediabetes found with this test is called IGT.

A blood glucose level between 7.8 mmol/l to 11.1 mmol/l indicates prediabetes.

The following table lists the blood test levels for a diagnosis of prediabetes.

Understanding Test Results

A blood test indicating prediabetes means that insulin resistance has progressed to the point where the beta cells in the pancreas can no longer compensate and a person's blood glucose levels are rising toward type 2 diabetes. The higher the test results, the greater the risk of type 2 diabetes. The level of risk also depends on an individual's other risk factors.

Test numbers: For example, people with an HbA1c below 5.7 percent may still be at risk for diabetes if they have a family history of type 2 diabetes or have gained excess weight around the waist. People with an HbA1c above 6.0 percent should be considered at very high risk of developing diabetes. A level of 6.5 percent or above means a person has diabetes.

Follow up: People whose test results indicate they have prediabetes may be retested in 1 year and should consider making lifestyle changes to reduce their risk of developing type 2 diabetes.

Varying results: Although all these tests can be used to test for prediabetes, in some people one test will indicate a diagnosis of prediabetes or diabetes when another test does not. People with differing test results may be in an early stage of the disease, where blood glucose levels have not risen high enough to show on every test.

Health care providers repeat laboratory tests to confirm test results. Diabetes develops over time, so even with variations in test results, health care providers can tell when overall blood glucose levels are becoming too high.

Can insulin resistance and prediabetes be reversed?

Yes. Physical activity and weight loss help the body respond better to insulin. The Diabetes Prevention Program (DPP) was a federally funded study of 3,234 people at high risk for diabetes.

The DPP and other large studies proved that people with prediabetes can often prevent or delay diabetes if they lose a modest amount of weight by cutting fat and calorie intake and increasing physical activity—for example, walking 30 minutes a day, 5 days a week.

People at High Risk for Diabetes

DPP study participants were overweight and had prediabetes. Many had family members with type 2 diabetes. Prediabetes, obesity, and a family history of diabetes are strong risk factors for type 2 diabetes. About half of the DPP participants were from minority groups with high rates of diabetes, including African Americans, Alaska Natives, American Indians, Asian Americans, Hispanics/Latinos, and Pacific Islander Americans.

DPP participants also included others at high risk for developing type 2 diabetes, such as women with a history of gestational diabetes and people ages 60 and older.

Prevention

Approaches to Preventing Diabetes

The DPP tested three approaches to preventing diabetes:

• Making lifestyle changes: People in the lifestyle change group exercised, usually by walking 5 days a week for about 30 minutes a day and lowered their intake of fat and calories.
• Taking the diabetes medication metformin: Those who took metformin also received information about physical activity and diet.
• Receiving education about diabetes: The third group only received information about physical activity and diet and took a placebo—a pill without medication in it.

People in the lifestyle change group showed the best outcomes. However, people who took metformin also benefited. The results showed that by losing an average of 7 kg (15 pounds) in the first year of the study, people in the lifestyle change group reduced their risk of developing type 2 diabetes by 58 percent over 3 years.

Lifestyle change was even more effective in those ages 60 and older. People in this group reduced their risk by 71 percent.

People in the metformin group also benefited, reducing their risk by 31 percent. (More information about the DPP below).

Lasting Results

The Diabetes Prevention Program Outcomes Study (DPPOS) has shown that the benefits of weight loss and metformin last for at least 10 years. The DPPOS has continued to follow most DPP participants since the DPP ended in 2001. The DPPOS showed that 10 years after enrolling in the DPP people in the lifestyle change group reduced their risk for developing diabetes by 34 percent those in the lifestyle change group ages 60 or older had even greater benefit, reducing their risk of developing diabetes by 49 percent participants in the lifestyle change group also had fewer heart and blood vessel disease risk factors, including lower blood pressure and triglyceride levels, even though they took fewer medications to control their heart disease risk those in the metformin group reduced their risk of developing diabetes by 18 percent.

Even though controlling weight with lifestyle changes is challenging, it produces long-term health rewards by lowering the risk for type 2 diabetes, lowering blood glucose levels, and reducing other heart disease risk factors.

What steps can help reverse insulin resistance and prediabetes?

By losing weight and being more physically active, people can reverse insulin resistance and prediabetes, thus preventing or delaying type 2 diabetes.

People can decrease their risk by:

• Eating a healthy diet and reaching and maintaining a healthy weight
• Increasing physical activity
• Not smoking
• Taking medication

Eating, Diet, and Nutrition

Adopting healthy eating habits can help people lose a modest amount of weight and reverse insulin resistance. Experts encourage people to slowly adopt healthy eating habits that they can maintain, rather than trying extreme weight-loss solutions. People may need to get help from a dietitian or join a weight-loss program for support.

In general, people should lose weight by choosing healthy foods, controlling portions, eating less fat, and increasing physical activity. People are better able to lose weight and keep it off when they learn how to adapt their favourite foods to a healthy eating plan.

The DASH (Dietary Approaches to Stop Hypertension) eating plan, developed by the NIH, has been shown to be effective in decreasing insulin resistance when combined with weight loss and physical activity. (More information on DASH is available below).

Physical Activity

Regular physical activity tackles several risk factors at once. Regular physical activity helps the body use insulin properly.

Regular physical activity also helps a person:

• lose weight
• control blood glucose levels
• control blood pressure
• control cholesterol levels

People in the DPP who were physically active for 30 minutes a day, 5 days a week, reduced their risk of type 2 diabetes. Many chose brisk walking as their physical activity.

Most people should aim for at least 30 minutes of exercise most days of the week. For best results, people should do both aerobic activities, which use large muscle groups and make the heart beat faster, and muscle strengthening activities.

Aerobic activities include brisk walking, climbing stairs, swimming, dancing, and other activities that increase the heart rate.

Muscle strengthening activities include lifting weights and doing sit-ups or push-ups.

People who haven't been physically active recently should talk with their health care provider about which activities are best for them and have a checkup before starting an exercise program.

Not Smoking

Those who smoke should quit. A health care provider can help people find ways to quit smoking. Studies show that people who get help have a better chance of quitting.

For more information about how to reverse insulin resistance and prediabetes with diet and increased physical activity, see the following National Diabetes Education Program publications:

Medication

The medication metformin is recommended for treatment of some individuals at very high risk of developing type 2 diabetes. In the DPP, metformin was shown to be most effective in preventing or delaying the development of type 2 diabetes in younger, heavier people with prediabetes.

In general, metformin is recommended for those who are younger than age 60 and have:

• Combined IGT and IFG
• Hba1c above 6 percent
• Low HDL cholesterol
• Elevated triglycerides
• A parent or sibling with diabetes
• A BMI of at least 35

Metformin also lowers the risk of diabetes in women who have had gestational diabetes. People at high risk should ask their health care provider if they should take metformin to prevent type 2 diabetes.

Several medications have been shown to reduce type 2 diabetes risk to varying degrees, but the only medication recommended by the ADA for type 2 diabetes prevention is metformin. Other medications that have delayed diabetes have side effects or haven't shown long-lasting benefits. No medication, including metformin, is approved by the U.S. Food and Drug Administration to treat insulin resistance or prediabetes or to prevent type 2 diabetes.

Points to Remember

• Insulin is a hormone that helps cells throughout the body absorb glucose and use it for energy. Insulin resistance is a condition in which the body produces insulin but does not use it effectively.
• Insulin resistance increases the risk of developing type 2 diabetes and prediabetes.
• The major contributors to insulin resistance are excess weight, especially around the waist, and physical inactivity.
• Prediabetes is a condition in which blood glucose or HbHbA1c levels—which reflect average blood glucose levels—are higher than normal but not high enough for a diagnosis of diabetes.
• The Diabetes Prevention Program (DPP) study and its follow-up study, the Diabetes Prevention Program Outcomes Study (DPPOS), confirmed that people with prediabetes can often prevent or delay diabetes if they lose a modest amount of weight by cutting fat and calorie intake and increasing physical activity.
• By losing weight and being more physically active, people can reverse insulin resistance and prediabetes, thus preventing or delaying type 2 diabetes.
• People with insulin resistance and prediabetes can decrease their risk for diabetes by eating a healthy diet and reaching and maintaining a healthy weight, increasing physical activity, not smoking, and taking medication.
• The DPP showed the diabetes medication metformin to be most effective in preventing or delaying the development of type 2 diabetes in younger and heavier people with prediabetes and women who have had gestational diabetes.

About the Source

This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.

Edited by: Dr George A. Bray, M.D., Pennington Biomedical Research Center, Louisiana State University & Dr Richard F. Hamman, M.D., Dr.P.H., University of Colorado Health Sciences Center

Recommended websites

For further reading go to:

• Tests for Blood Sugar (Glucose) and HbHbA1c
• Calculate Your Body Mass Index
• More information about the Diabetes Prevention Program (DPP)
• Manage your diabetes

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