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What is insulin resistance and how does it cause diabetes?








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What is insulin and how does it work?

Insulin is a small naturally occuring chemical in our body. Insulin acts like a key, whose purpose is to bind to a receptor (the lock) on the surface of fat and muscle cells. When insulin binds to the insulin receptor, it opens a glucose channel to allow glucose to enter those cells. This process is how we get glucose from our blood stream (after it has been broken down from the food we eat) into the cells of our body, to provide our body with energy.

In this article

Insulin resistance
Causes
Complications
Who is at risk
Can it be reversed
Reducing insulin resistance
Diagnosis
Prediabetes
Metabolic Syndrome
Type 2 diabetes


How does insulin work


What is insulin resistance?

As Dr Sultan describes in the video, insulin resistance occurs when your fat cells become resistant to the effects of insulin. This resistance occurs because the fat cells have changed the shape of the insulin receptor, to prevent glucose from entering into the fat cell.

The process of the lock changing shape is called insulin resistance. The effect of this is more insulin is needed to force the receptor to work. The pancreas needs to produce more insulin resulting in accelerated pancreatic failure and possibly diabetes.



What are the causes of insulin resistance?

Insulin resistance most commonly is associated with obesity. Insulin resistance may also result from multiple underlying causes. These include:

  • obesity associated
  • ageing
  • polycystic ovarian syndrome
  • stress induced
  • some medications like steroids
  • pregnancy
  • lipodystrophy
  • insulin antibodies


What are the complications of insulin resistance?

Consequences of obesity-related insulin resistance includes:



Who is at risk of insulin resistance?

Prediabetes and type 2 diabetes is a journey. There are some people who are more likely to develop diabetes compared to others. People who are overweight or obese are more likely to develop diabetes, so to prevent type 2 diabetes you either want to stay a healthy weight or else you want to lose weight. The longer you are overweight the more likely you are to develop insulin resistance and the longer you have insulin resistance the more likely you are to develop pancreatic dysfunction, leading to type 2 diabetes.

Aside from weight, there are several factors that can increase your risk of developing insulin resistance. They are referred to as being either modifiable risk factors or non-modifiable risk factors.


Non-modifiable risk factors

Non-modifiable risk factors are risk factors that can’t be changed. These include:

  • Family history
  • Genetics
  • Age
  • Gender

Being aware of the non-modifiable risk factors is extremely important. For people who have a family history of type 2 diabetes, you need to be more alert and start taking action early to prevent or delay developing prediabetes and type 2 diabetes.


Modifiable risk factors

Modifiable risk factors can be modified or changed in some way. For example, if you are someone who doesn’t exercise, then you may begin to exercise 2-3 times per week. This means you have modified your behaviour and lifestyle!

Modifiable risk factors include:

  • Being overweight or obese, particularly extra weight around the waist – i.e. waist circumference more than 94cm (37in) for men and more than 80cm (31in) for women
  • Having high blood pressure
  • Having high cholesterol and high triglycerides
  • Being physically inactive
  • Eating a poor diet (one that is high in fat, salt, and sugar)


Can insulin resistance be reversed or changed?


Yes!

If you lose weight and you shrink your fat cell, the insulin receptor (lock) will eventually change back to it's original shape. This means that insulin (the key) will be able to fit nicely in the lock again!

You may often hear people talking about 'reversing diabetes.' What they are really talking about is sustained weight loss. Sustained weight loss can lead to the improvement of the shape of the insulin receptor (lock).



What can I do to reduce insulin resistance?

Dr Sultan talks about how sustained weight loss can show a profound improvement on glucose levels. There are a few actions that you can take to achieve a reduction in weight.

There are changes you can make to improve your health and reduce insuling resistance and reduce your risk of developing diabetes. These include:

  • Use of metformin medication
  • Eating well
  • Moving your body more
  • Being a healthy weight
  • Setting realistic goals
  • Getting support
  • Make changes part of your everyday


How is insulin resistance diagnosed

Insulin resistance is diagnosed by a blood test that measures either the fasting insulin level in the morning or by measuring glucose and insulin levels as part of a glucose tolerance test. Testing for insulin resistance is not always done and a diagnosis can be made based on the certain features that a person may demonstrate.


Insulin Levels

Insulin levels indicate resistance
Fasting 2 hour GTT
Normal less than 10 less than 60
Inconclusive 10-20 60-100
Insulin Resistant more than 20 more than 100


Insulin resistance occurrs before a person develops type 2 diabetes, when they have borderline diabetes (impaired glucose tolerance) as well as when type 2 diabetes exists.

Features associated with insulin resistance include:

  • weight gain around the abdomen
  • skin tags
  • acanthosis nigricans
  • thickened skin
  • irregular periods if associated with PCOS (polycystic ovarian syndrome)
  • features consistant with endocrine conditons such as acromegaly and Cushing's syndrome


Skin Tags

Skin tags are often associated with insulin resistance and metabolic syndrome, and are frequently seen in obese patients and in patients with diabetes mellitus.

Skin tags are an outgrowth of normal skin. They usually occur in sites of friction, particularly the armpit, neck, under breasts, and in the groin.

Skin tags are diagnosed based upon clinical appearance and treatment is recommended if the skin tags are irritating or removal is desired for cosmetic reasons.


Example 1 - Skin tags


Example 2 - Skin tags


Acanthosis Nigricans

Acanthosis nigricans is characterized by velvty, hyperpigmented plaques on the skin. Like skin tags, acanthosis nigricans is commonly found in areas of the body where two skin areas rub together, including the neck, arm pits, under breasts, and the groin.

Obesity and diabetes are the most common medical disorders linked with acanthosis nigricans, where insulin resistance is likely responsible for the development of acanthosis nigricans.


Example 1 - Acanthosis Nigricans


Example 2 - Acanthosis Nigricans


Polycystic Ovarian Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is the most common cause of infertility in women. It frequently manifests during adolescence, and is primarily characterized by ovulatory dysfunction and hyperandrogenism (high levels of androgens, which are steroid hormones for example testosterone).

PCOS is associated with a number of varied clinical features, including:

  • Cutaneous signs of hyperandrogenism (eg, hirsutism, moderate-severe acne)
  • Menstrual irregularity (eg, oligo- or amenorrhea, or irregular bleeding)
  • Polycystic ovaries (one or both)
  • Obesity and insulin resistance

The diagnosis of PCOS has lifelong implications with increased risk for metabolic syndrome, type 2 diabetes mellitus, and, possibly, cardiovascular disease and endometrial carcinoma (cancer) (Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis).

PCOS is associated with insulin resistance and high insulin levels. Obesity and clinical manifestations of insulin resistance, for example skin tags and acanthosis nigricans, are strongly associated with PCOS. Adolescents with PCOS are at an increases risk for glucose intolerance and type 2 diabetes and approximately 10% of women with PCOS will have type 2 diabetes by 40 years.




Insulin resistance, Prediabetes (borderline diabetes), and Type 2 Diabetes Mellitus

Insulin resistance may be the best predictor for type 2 diabetes. Before someone is diagnosed with type 2 diabetes, they may be diagnosed with Prediabetes.

Beginning with prediabetes, type 2 diabetes is a progressive disease that develops over many years. It is also a complex condition, affecting many parts of your body. When people are diagnosed with type 2 diabetes mellitus, the disease process may have been present for 5-10 years. This means some complications may already be present at diagnosis.



What is Prediabetes, also known as borderline diabetes?

Prediabetes is a condition that describes a person who has a number of abnormal glucose blood tests suggesting they have borderline diabetes. It may also be called “impaired glucose tolerance” or “metabolic syndrome”. People with prediabetes are very likely to progress to developing type 2 diabetes in the coming few years. More importantly, people with prediabetes are the most likely to recover and return back to normal by making a few important changes.



What is metabolic syndrome?

Metabolic syndrome, sometimes called syndrome X, is a collection of disorders, including high blood pressure, insulin resistance, abnormal cholesterol levels, and excess fat around the waist. People with metabolic syndrome are twice as likely to have a heart attack and stroke, and five times more likely to develop type 2 diabetes, compared to people without metabolic syndrome.



metabolic syndrome is a combination of obesity, insulin resistance, high blood pressure, and high cholesterol


Over the past three decades, the prevalence of Metabolic Syndrome has increased. Did you know that children and adolescents can also have metabolic syndrome? It’s not just adults! More and more young people are showing signs of metabolic syndrome. The incidence of metabolic syndrome often parallels the incidence of type 2 diabetes and obesity (The Global Epidemic of the Metabolic Syndrome). According to the Centers for Disease Control and Prevention (CDC), 12.2% or 30.2 million adults (aged 18 years and older) in the USA had type 2 diabetes in 2017. What’s scary, is that a quarter of these adults, don’t even realise that they have diabetes.

Typically, adults with type 2 diabetes will present with comorbidities such as obesity, hypertension (high blood pressure), and dyslipidemia (elevated cholesterol and fats in the blood). A comorbidity is the presence of one or more additional diseases or disorders. Other comorbidities that may be present at diagnosis or can develop over time, include gum disease, sleep apnoea, fatty liver disease, depression and anxiety, and bone fractures (Comprehensive Medical Evaluation and Assessment of Comorbidities by the American Diabetes Association).

If there are any complications present in a person with diabetes, the disease progression can be slowed by interventions, for example better management of blood glucose levels, blood pressure, and blood lipids.



What is Type 2 Diabetes?

Type 2 diabetes explained simply

Like prediabetes, Type 2 diabetes is an elevation in blood sugars that occurs when glucose can’t get into your fat and muscles where it is needed. Elevated blood glucose damages the lining of blood vessels leading to a range of complications in various organs of the body.


Type 2 diabetes explained in detail

Type 2 diabetes is rapidly becoming of the most common long-term disease in the world. The problem causing an elevation in the blood glucose levels occurs when there is a change in the shape of the insulin receptor. In the normal situation, the body produces a small chemical called insulin (key) whose purpose is to bind to a receptor (lock) on the surface of fat and muscle cells, opening a channel to allow glucose to enter those cells. In type 2 diabetes the shape of this receptor changes mostly as a consequence of weight gain around the stomach. As we have discussed, the process of the lock changing shape is called Insulin Resistance.


Type 2 diabetes is a progressive disease. If left untreated, the pancreas will begin to fail and no longer be able to produce insulin, contributing to the increased glucose levels in the blood.

in type 2 diabetes, the pancreas produces less insulin which results in less glucose moving from the blood stream into the cells


Symptoms of Type 2 diabetes

In diabetes mellitus, symptoms that you experience are related to:

a) the severity of diabetes, i.e. how high your blood glucose levels are,

and

b) how long you have had the condition, i.e. how long you have had high blood glucose levels for.

In people with type 2 diabetes, the progression of the condition happens much more slowly, over the course of several years, so the symptoms happen slowly and are often subtle. You may not even notice anything at all, or you may even dismiss them as a normal part of growing older.

By the time that you notice something isn’t quite right, you could have been experiencing high blood glucose levels for years! Often people who are diagnosed with type 2 diabetes, have had diabetes for perhaps 5 years and borderline diabetes for many years before that.



What is the most common symptom in people with type 2 diabetes?

The most common sign of diabetes is…

Nothing.

That’s right. Nothing. The reason that doctors need to test for diabetes (and people need to demand it), is that most people have no idea that they have it. This regular testing is most important in people at the highest risk of developing diabetes.

If you want to learn how type 2 diabetes mellitus can affect men and women differently, we can also written dedicated artcles to answer your questions:

Dr Sultan also has a helpful video discussing the symptoms of diabetes. To learn more, watch the What are the symptoms of diabetes? video.



Type 2 diabetes complications

Diabetes is a vascular disease which means it affects blood vessels. Complications in type 2 diabetes can be described as microvascular (small blood vessels) or macrovascular (large blood vessels) complications (Microvascular and Macrovascular Complications of Diabetes). Diabetes-related complications occur over time due to persistent high blood glucose levels, high blood pressure, and abnormal cholesterol levels. These complications are serious and can be life-threatening.


Macrovascular complications - Problems with large blood vessels

Macrovascular disease affects the larger blood vessels in our body that supply blood to the heart, brain, and legs. Macrovascular complications include:

  • Coronary artery disease which can lead to a heart attack
  • Cerebrovascular disease which can lead to a stroke
  • Peripheral artery disease which can lead to pain deep in the leg muscles (calves, thigh, or buttocks) during activity as well as amputations.

Microvascular complications – problems with small blood vessels

Like macrovascular disease, ongoing high blood glucose levels are an important risk factor for the development of microvascular disease in patients with type 2 diabetes. Microvascular complications include:

  • Retinopathy – Disease of the eye which can lead to blindness
  • Neuropathy – Disease of the nerves which can lead to foot ulcers requiring amputation
  • Nephropathy – Disease of the kidneys which can lead to kidney failure and the need for dialysis

Hb A1c and complications in type 2 diabetes

Higher Hb A1c readings are also linked to an increased risk of complications. You can read about Hb A1c and the risk of developing type 2 diabetes complications to learn more.



Video Transcript

So one of the things that happens to people with Type 2 diabetes or people with pre-diabetes or borderline diabetes is a long time before developing the condition they develop a thing called insulin resistance.

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I want to explain a little bit about how insulin resistance works and why it occurs because I think there are a few important aspects that are worth knowing about. So with everything with diabetes we really start with food. If that food is excessive to our current needs we will break it down and we will store it inside a fat cell. And the way that we get particularly carbohydrates into fat cell is there is a lock on the surface of the cell called the insulin receptor. So when insulin as a lock binds to insulin which is like a key the two bind together and that actually opens a channel that allows food to get into the cell. Now if we eat excessive amounts of food then what will typically happen is that fat cell will increase in size.

If we continue to eat excessive amounts of food then that fat cell will get bigger and bigger and bigger. And eventually it will get to the point that even if the fat cell wants to just keep on growing it is constrained by its physical size, it cannot just get bigger. And at that point the fat cell is in trouble. Because it has to find a way to prevent excessive amounts of energy particularly in the form of glucose and carbohydrate from getting into the fat cell. And the way that is occurring is it changes the shape of the lock and you create this process of insulin resistance. Your fat cells become resistant to the effect of insulin so you produce a large amount of insulin just to try to open that lock.

Now over time what happens is the pancreas produces extra insulin and then eventually it cannot continue to produce the high amounts of insulin that it needs and the pancreas starts to fail and specifically the pancreatic insulin production starts to fail and the blood sugars rise.



Can insulin resistance be changed?

Well the answer is if you lose weight and you shrink your fat cell and you continue to shrink the fat cell then eventually what will happen is the lock will go back to normal and the insulin will be able to fit nicely.

And so when people talk about reversing diabetes they are really talking about sustained weight reduction that leads to improvement of the shape of the lock.

Now it may be that the pancreatic function by the time a person decides that they really want to deal with their diabetes is so diminished that they are not going to be able to produce enough insulin even with a well working lock. But nonetheless if you can reduce insulin resistance there really is quite a profound improvement in glucose levels that a person can expect and the earlier that you deal with insulin resistance the better.

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