How does insulin resistance lead to prediabetes, diabetes, and metabolic syndrome

We define Insulin resistance as a less than normal response to normal insulin concentrations. Prediabetes is the condition between insulin resistance and diabetes. Metabolic syndrome is a combination of metabolic derangements such as high blood pressure and high cholesterol. Insulin resistance eventually leads to a prediabetes state. So, when someone has prediabetes even an elevated amount of insulin cannot keep blood sugar levels at normal levels. Metabolic syndrome finally develops when you have a combination of insulin resistance that results in high glucose, high blood pressure, and abnormal cholesterol.

Let’s review these conditions in detail.  

Prediabetes and insulin resistance first came into use several years after the introduction of insulin therapy in 1922. At that time some patients required excessive amounts of insulin. This brought the concept of insulin resistance. Since then we learned a lot about insulin resistance and prediabetes.

This topic will review the definition, clinical features, and diagnosis of insulin resistance. Possible mechanisms for the development of insulin resistance are discussed in our previous blog article.

Definition of prediabetes, metabolic syndrome, insulin resistance, and their causes

There are 3 different tests that can help doctors tell whether a person might develop type 2 diabetes. All 3 tests measure blood sugar in different ways. “Blood glucose” is another name for blood sugar.

Even though these tests can help predict diabetes or prediabetes, they are not appropriate for everyone. Your diabetes doctor will decide if one of these tests is right for you. Often, people who we test are overweight and have another risk factor for diabetes. Examples of risk factors include having a history of diabetes during pregnancy or a family history of diabetes.

If a blood test shows that a person’s blood sugar is higher than normal but not high enough to be called diabetes, we call it “pre-diabetes.” People with pre-diabetes are at high risk of developing diabetes. Prediabetes is often a result of insulin resistance and also is part of metabolic syndrome.

What are the tests that define insulin resistance or prediabetes?

• Fasting glucose test – This test measures your blood sugar when you have not had anything to eat or drink (except water) for 8 hours. People with pre-diabetes have a fasting glucose between 100 and 125.
• Glucose tolerance test – For this test you do not eat or drink anything for 8 to 12 hours. But then, as part of the test, you have a sugary drink. Two hours later, a doctor or nurse takes a blood sample to see how high your blood sugar got. People with prediabetes have glucose tolerance results between 140 and 199.
• Hemoglobin A1C test (also called HbA1C or A1C) – For this test it does not matter whether you eat beforehand. It is a blood test that shows what your average blood sugar level has been for the past 2 to 3 months. People with pre-diabetes have A1C levels between 5.7 and 6.4.

Risk factors for prediabetes and insulin resistance and metabolic syndrome

Both prediabetes and insulin resistance most commonly occur in association with obesity. But, they may result from multiple other underlying causes. We have listed These Causes below.

• Obesity-associated
• Stress-induced (due to excess counterregulatory hormones cortisol, growth hormone, catecholamines, glucagon)
• Medications (eg, glucocorticoids, human immunodeficiency virus [HIV] antiretrovirals, oral contraceptives)
• Pregnancy (placental Hormones)

Clinical features of prediabetes and insulin resistance

Insulin resistance can present in a variety of ways depending on the underlying cause and severity. The consequences of obesity-related insulin resistance are multiple. Some of them are elevated glucose levels, type 2 diabetes mellitus, increased insulin requirements in type 1 diabetic patients.

Diseases and syndromes associated with insulin resistance

Patients with insulin resistance and prediabetes are at increased risk of many other health problems. Below you will see a list of disorders associated with prediabetes and insulin resistance.

• Coronary artery disease
• Metabolic syndrome
• Polycystic ovary syndrome (PCOS)
• Nonalcoholic fatty liver disease
• Certain obesity-related cancers

Sometimes patients may have a genetic cause for insulin resistance. Genetic syndromes typically have extreme insulin resistance and therefore more severe phenotypes.

What is the link between insulin resistance and other diseases?

In most cases, we do not know the precise basis for the link between insulin resistance and clinical findings such as heart disease.  We believe that elevated insulin levels due to insulin resistance can over-stimulate other organs in the body. This can lead to disturbance in other organ systems. For example, excessive insulin levels can go over to stimulate the ovaries.  Overstimulated ovaries produce too much testosterone.  Too much testosterone, in turn, causes problems in the menstrual irregularities.  It can also lead to excessive hair. We call this PCOS. Namely, polycystic ovarian syndrome.

Distribution of Fat in the body plays a role

In obesity-related insulin resistance, central or abdominal obesity is common. We also see fat deposition in muscle and liver. Although the mechanism by which obesity induces insulin resistance is not totally clear to many.

Abdominal obesity induces inflammation and results in fatigue

An increasing number of individuals in Western societies have general obesity and/or abdominal obesity. High serum free fatty acid concentrations in the circulation and/or excess fat deposition in muscle or liver seem to be responsible for insulin resistance and prediabetes. Free fatty acids come from enlarged adipose cells. When the storage capacity of fat cells overflows fatty acids start circulating in the blood. The body’s defense system( immune cells) tend to be attracted to areas with fat deposition. When bodies defense systems meet fat cells areas a clash happens. Immune cells start eating up fat cells which lead to inflammation. Inflammation creates a state of fatigue. As a result, most patients with obesity or excessive fat deposition complain from excessive tiredness.

Abdominal obesity reduces good chemicals that prevent heart disease.

There are certain Good chemicals within fat cells. During the process of inflammation but he uses these good chemicals as well. We call these good chemicals adiponectin. Adiponectin levels go down with excess belly fat accumulation. Adiponectin increase with healthy dietary patterns and exercise. Low adiponectin levels are associated with high circulating levels of insulin, inflammatory chemicals. Eventually, this process leads to obesity and insulin resistance-related problems in genetically predisposed individuals.

Abnormal glucose metabolism/prediabetes

Every patient’s response to obesity can be different. Some patients start developing elevated glucose levels with slight insulin resistance. Some other patients may have all the signs of insulin resistance without any glucose changes until very late stages. This is determined by genetics. When glucose levels start to go up we call that prediabetes.

Why does Obesity lead to prediabetes?  

Obesity, particularly abdominal obesity can cause derangement in insulin action. Prediabetes follows insulin resistance. Later, prediabetes leads to type 2 diabetes mellitus if obesity remains or worsens. Many patients with obesity-related insulin resistance initially have normal or only slightly high blood glucose concentrations. In many cases, however, pancreatic beta cells (insulin-making cells) eventually fail to compensate for insulin resistance. This causes high blood sugars. Patients may have impaired fasting glucose or elevated glucose levels after meals prior to developing overt type 2 diabetes. Some patients eventually require large doses of insulin to control high blood sugar after being diabetic.

What is metabolic syndrome or syndrome X

 The metabolic syndrome is defined as the co-occurrence of metabolic risk factors for both type 2 diabetes and cardiovascular risk factors. Cardiovascular risk factors are abdominal obesity, hyperglycemia, dyslipidemia, and hypertension. All of these factors go side by side. Insulin resistance is the common denominator of all.

As we discussed, abdominal obesity causes insulin resistance. Insulin resistance then causes high insulin levels with high blood sugars. Also, fat tissue creates inflammation due to an immune attack. This inflammation and high insulin levels may lead to vascular destruction. Also, the same factors lead to high cholesterol, hypertension, and vascular inflammation. All of these factors promote the development of cardiovascular disease (CVD).

What are the signs of prediabetes and  insulin resistance

Acanthosis nigricans as a sign of insulin resistance

Acanthosis nigricans is a brown/darker color soft/velvety skin on the neck or under armpits.  Skin tags and acanthosis nigricans are common with insulin resistance. The lesions are usually found on the back of the neck, the axilla (picture 1), the groin, and over the elbows. But, they may cover the entire surface of the skin, sparing only the palms and soles.

The common denominator in all cases of acanthosis nigricans, with the possible exception of tumor-induced lesions, is insulin resistance.

Diagnosis of Metabolic Syndrome

Obesity-related insulin resistance — The diagnosis of insulin resistance in most patients is based upon clinical findings (eg, metabolic syndrome traits):

• High blood sugars
• High cholesterol levels
• Abdominal obesity
• Hypertension/High blood pressure

In a clinical setting, it would be useful to quantify insulin resistance in obese patients. Obese patients are at the highest risk for the development of type 2 diabetes mellitus and its complications. The worst complication of insulin resistance is cardiovascular disease (CVD) and cancers. Some common cancers associated with insulin resistance are colon, breast, and endometrial cancers).

In nondiabetic overweight individuals, we use serum triglyceride concentration, the ratio of triglyceride to high-density lipoprotein (HDL) cholesterol concentrations, and fasting insulin concentration for identifying insulin resistance. Optimal cut-points were identified as 130 mg/dL, 3.0, and 15.7 microU/mL  for triglycerides, triglyceride-to-HDL ratio, and insulin, respectively.

 

What should I do if I have pre-diabetes and what diet is best for prediabetes?

If you have pre-diabetes, metabolic syndrome or insulin resistance, make lifestyle changes. Do so to reduce the chance that you will get full-blown diabetes. Here are a few things you can do.

• Lose weight – Losing 5 to 10 percent of your body weight can lower your risk a lot. If you weigh 180 pounds that means you should lose 9 to 18 pounds. If you weigh 160 pounds, that means you should lose 8 to 16 pounds.
• Eat right – Choose a diet rich in fruits, vegetables, and low-fat dairy products, but low in meats, sweets, and refined sugar. Stay away from sweet drinks, like soda and juice.
• Exercise for 30 minutes a day – You don’t have to go to the gym or break a sweat to get a benefit. Walking, gardening and dancing are all activities that can help.
• Quit smoking – If you smoke, ask your doctor or nurse for advice on how to quit. People are much more likely to succeed if they have help and get medicines to help them quit.
• If your doctor or nurse prescribed any medicines, take them every day, as directed. Most common medication that helps the prevention of diabetes is metformin. That goes for medicines to prevent diabetes, and for ones to lower blood pressure or cholesterol. People with pre-diabetes have a higher-than-average risk of heart attacks, strokes, and other problems, so those medicines are important.

What diet is best for prediabetes?

Mediterranean diet is the best. To go into more diet details here is a good summary. Please also refer to our diabetes and diet blog.

When planning what to eat, people with pre-diabetes, insulin resistance, and metabolic syndrome need to think about carbs, protein, and fat.

Carbohydrates (or “carbs”) –

Carbohydrates, which are sugars that our bodies use for energy, can raise a person’s blood sugar level. Your doctor, nurse, or dietitian will tell you how many carbohydrates you should eat at each meal or snack. Most prediabetic patients should limit total carbs per to less than 45 grams per meal.

Foods that have carbohydrates include:

• Bread, pasta, and rice
• Vegetables and fruits
• Dairy foods
• Foods with added sugar

It is best to get your carbohydrates from fruits, vegetables, whole grains, and low-fat milk.

Protein

Your doctor, nurse, or dietitian will tell you how much protein you should eat each day. We recommend 50-75 gr of total protein daily. It is best to eat lean meats, fish, eggs, beans, peas, soy products, nuts, and seeds.

Fats

The type of fat you eat is more important than the amount of fat. “Saturated” and “trans” fats can increase your risk for heart problems, like a heart attack.

Foods that have saturated fats include meat, butter, cheese, and ice cream. Avoid them.

Foods that have trans fats include processed food with “partially hydrogenated oils” on the ingredient list. This may include fried foods, store-bought cookies, muffins, pies, and cakes.

“Monounsaturated” and “polyunsaturated” fats are better for you. Foods with these types of fat include fish, avocado, olive oil, and nuts.

SUMMARY

Insulin resistance or metabolic syndrome is a state in which a given concentration of insulin is not enough for a normal glucose response. Important long-term consequences of insulin resistance include the development of prediabetes, type 2 diabetes, cardiovascular disease (CVD), and certain cancers associated with obesity.

Insulin resistance is associated with a variety of clinical presentations based on its severity.

For patients with obesity, the diagnosis of insulin resistance is based on clinical findings. These clinical factors include eg, High blood sugars High cholesterol, abdominal obesity, and hypertension.

So if you are overweight, having problems losing weight, feeling fatigued and not having the energy to do anything, then you are more than likely to have insulin resistance.  In your blood work you will see low HDL, sometimes elevated triglycerides and your cholesterol profile.  Your blood sugars may start to go up and your doctor may tell you that you have prediabetes or diabetes in a worst-case scenario.  Blood pressure generally follows insulin resistance and abnormal cholesterol levels. As a result, most people start developing cardiovascular disease and even have heart attacks before they get diagnosed with diabetes.  Most heart attacks have been in the prediabetes stage.  It is very important for you to take action.  Seeing an endocrinologist early on will save you a lot of headaches and trouble in the future.