Insulin is an essential hormone that we cannot live without. What happens, however, when our tissues have trouble responding to it? That’s insulin resistance.
Insulin resistance is a very common condition that often accompanies obesity or a diagnosis of pre-diabetes, type 2 diabetes, polycystic ovary syndrome (PCOS), cardiovascular disease, and other metabolic conditions such as hypertension and non-alcoholic fatty liver disease.
Have you been told you have insulin resistance? You’re not alone.
What is insulin resistance?
Insulin resistance is when cells in your body do not respond effectively to the hormone insulin that is circulating in your body. This causes the pancreas to secrete even more of this important hormone in an effort to keep your blood sugar from rising too high.
Insulin has many roles. Its primary role is to keep our blood glucose levels in a very tight range — called blood glucose homeostasis. That’s because both too high and too low blood glucose levels are dangerous and damaging to the body. When glucose levels rise, more insulin is secreted. When glucose levels fall, less insulin is secreted. Since higher levels of insulin have been associated with numerous chronic health conditions, it makes sense that keeping insulin in a lower physiologic range may be better for your long-term health.
Insulin also enables glucose to be used by cells for fuel or stored as glycogen in muscle and liver cells. Falling levels of insulin let the liver know when to make more glucose (gluconeogenesis) and rising insulin levels let the liver know when to stop.
Another crucial role is insulin’s regulation of fat storage. When insulin levels are high, it stimulates fat cells to take up glucose and turn it into fat (lipogenesis). Then, when insulin is low, it enables the body to take the fat out of storage and use it for energy.
For someone who is metabolically healthy, this process works seamlessly to ensure a constant supply of fuel for the body.
Why does insulin resistance happen?
Genetic risk factors, environmental risk factors, and lifestyle factors have all been found to contribute to the development of insulin resistance.
While some people may be genetically more likely to develop insulin resistance, the biggest impact has perhaps come from the change in our food environment in recent decades. Greater availability of cheap, energy-dense food and drinks may have led whole populations to adopt an unhealthy lifestyle, characterized by consumption of high levels of sugar and other refined carbohydrates. These simple carbohydrates are converted into large amounts of glucose that we may not need for energy, often resulting in much of it being stored in our cells or stored as fat.
Scientists have elucidated many mechanisms and pathways that contribute to the development of insulin resistance. Interestingly, although we often think of insulin resistance in terms of the effect of insulin on glucose metabolism, one of the major causes is actually disordered fatty acid metabolism.
Scientific evidence suggests that fatty acids inappropriately accumulate in muscle and liver which then interferes with their cells’ ability to respond to insulin and take up glucose.
One of the main questions, therefore, is how do excess fatty acids invade muscle and liver cells?
One mechanism involves the over-consumption of sugar, especially fructose, and particularly in the setting of excess caloric intake.
Through multiple pathways that are beyond the scope of this article, this is thought to lead to excessive production of fat in the liver, which then leads to increased insulin resistance.
The same is likely true for a high carbohydrate, high fat diet in the setting of excess calories. Some studies suggest that specifically saturated fat – more so than MUFAs and PUFAs – is the offender that causes insulin resistance.
Nonetheless, it is important to note that none of those studies included saturated fats in the context of a low-carb diet. Real world studies of low-carb diets with no restrictions on saturated fat have found improvements and even normalization of insulin resistance markers.
This suggests that the problem may not be saturated fat itself, but rather the combination of saturated fats and a high amount of carbohydrates.
Saturated fat from cakes, cookies, and other baked goods could have significantly different effects on the body than more natural occurring saturated fats in meat and dairy.
Finally, a critical concept to understand is that elevated insulin itself may worsen insulin resistance.
This creates a vicious cycle of insulin resistance and hyperinsulinemia likely made worse by ongoing caloric excess and weight gain.
Symptoms of insulin resistance
Insulin resistance has no obvious symptoms of ill health.
The main sign of the condition in many people — prior to being diagnosed with pre-diabetes or full-blown type 2 diabetes — is increasing abdominal fat, although not everyone will be aware of this.
A prevailing theory of how insulin resistance worsens is that we each have a threshold level of fat that can be stored in our fat cells and when this is exceeded, our body starts storing fat in less ideal places — especially around the organs in our abdomen (such as the liver and the pancreas) and in our abdominal cavity. This is called visceral fat and when this fat starts increasing, it is a sure sign of insulin resistance.
Other subtle signs of insulin resistance in some people are dark, dry patches of skin on the groin, armpits, or back of the neck, known as acanthosis nigricans.
Skin tags — small fleshy growths — often on the neck or armpits can also be a sign of insulin resistance in some people, which is thought to occur because insulin is a stimulator of cell growth.
Other than those symptoms, most people with early insulin resistance feel fine. It is only as blood glucose finally starts to rise that other symptoms of high blood sugar and type 2 diabetes may begin to show, such as frequent urination, excessive thirst, fatigue, and excessive hunger.
Conditions associated with insulin resistance
The following health conditions are associated with insulin resistance:
- Obesity — Insulin resistance is associated with high insulin levels that may lead to increased body weight and obesity; obesity in turn leads to increased insulin resistance, thus creating a vicious cycle.
- Pregnancy — Many women show signs of insulin resistance during pregnancy, especially in the third trimester.
This is believed to be an evolutionary adaptation to provide sufficient glucose to the rapidly growing fetus. However, in some people, this can lead to gestational diabetes and high blood pressure.
Proponents of the low-carb lifestyle believe this is a perfect example of how a normal adaptation designed to help ensure healthy pregnancy makes us more susceptible to metabolic disease in the context of a modern diet with foods high in refined carbohydrates, fats and sugars.
- Metabolic syndrome — This describes a collection of characteristics that are found in people with insulin resistance. There are a number of different definitions for metabolic syndrome that usually include an elevated fasting blood glucose level, high blood pressure, raised triglycerides and reduced HDL cholesterol, and increased waist circumference.
- Pre-diabetes — Insulin resistance is associated with pre-diabetes. This is a situation in which blood glucose levels are higher than normal but not yet high enough for a diagnosis of type 2 diabetes. The World Health Organization defines pre-diabetes as a fasting glucose of 110 – 125 mg/dL (6.1 – 6.9 mmol/L) or a 2-hour glucose of 140 – 200 mg/dL (7.8 – 11.1 mmol/L), as measured after a standardized 75-gram oral glucose challenge.
The US and some other countries use a different definition of FBG 100 – 125 mg/dL (5.7 – 6.9 mmol/L) or HbA1c 5.7 – 6.4% (39 – 46 mmol/mol). Since a diagnosis of pre-diabetes depends on an elevated blood glucose level, it implies that insulin levels have been chronically elevated for some time before the diagnosis.
- Polycystic ovary syndrome (PCOS) — Polycystic ovary syndrome (PCOS) is a common metabolic disorder affecting up to 10% of women of childbearing age. It’s a leading cause of infertility, and increases the risk of developing type 2 diabetes in later life.
Women with PCOS tend to have elevated levels of male hormones, irregular or absent menstrual periods, and cysts on their ovaries, as well as insulin resistance. Other common symptoms are obesity, acne, male-pattern hair loss, and excess facial and body hair.
- Non-Alcoholic Fatty Liver Disease — Called NAFLD, this is where there is too much fat stored in the liver. It may be the result of chronically high insulin levels and it may contribute to insulin resistance. While it is more common in individuals with obesity, metabolic syndrome, and type 2 diabetes, it has been found to be associated with insulin resistance and hyperinsulinemia in lean individuals with normal glucose tolerance.
Some people with NAFLD go on to develop liver problems, such as inflammation, scarring, and cirrhosis as well as liver failure.
- Cancer — Insulin resistance is associated with an increase in risk of colorectal cancer, endometrial cancer, pancreatic cancer, and breast cancer.
It is not clear whether it is the insulin resistance itself or its relationship to other risk factors, such as obesity and high blood glucose, that contributes to the increased cancer risk. However, it is thought that chronically high levels of insulin may promote cancer growth and that reducing insulin levels may slow cancer growth, although more data are needed in this area to draw firm conclusions