What is Insulin Resistance?

Insulin is a hormone that plays a dominant role in regulating various metabolic processes including blood sugar and body fat percentage. Under normal circumstances, this process is highly dynamic and constantly fine-tuned by the body. However, under certain conditions, the body becomes blunted to the regulatory effects of insulin. When this happens, the normal mechanism starts to fail and ‘insulin resistance’ sets in. As a result, blood sugar levels start to climb.

To compensate the body increases its production of insulin, thereby causing insulin levels to rise. When it comes to regulating blood sugar, rising insulin levels are beneficial since it helps keep rising blood sugar under control. However, when it comes to regulating body fat percentage, rising insulin levels spell somewhat of a disaster. This is because the hormone insulin not only makes the body more effective at storing fat but also makes it more difficult to burn fat.

The net effect is that your metabolism effectively slows down.

How is metabolism regulated?

All biochemical processes that take place in the body are initiated and controlled by a complex communication system that relies on messenger molecules that are able to convey biochemical instructions. Examples of messenger molecules are hormones, neurotransmitters and cytokines. Chemicals contained within pharmaceutical drugs or medicinal plant extracts also achieve their results through the same mechanism.

Depending on their design, messenger molecules deliver their biochemical communication either broadly at a high level to a large audience, or more selectively at a local level in a more specific manner. They can also override or overrule each other, as well as strengthen or amplify another’s message.

Metabolism is a complex process which involves the regulatory activity of various different messenger molecules. It is commonly believed that the thyroid gland is in charge of this process. This misguided view is based on oversimplification, since the numerous regulatory tasks that insulin performs relating to carbohydrate, protein and fat metabolism, as well as how insulin overrules virtually all other messenger molecules involved in the process, makes insulin the single most dominant controller of metabolism.

What causes insulin resistance?

Whilst genetic makeup, increasing age and certain disease states make you more prone to developing insulin resistance, lifestyle factors that lead to weight gain from the ultimate triggers. These include diet and a sedentary lifestyle. At the heart of the problem is excess body fat, not because of the space that it consumes within the body, but because excess body fat starts to release a range of messenger molecules that not only initiates a pathological communication process within fatty tissue itself but as a secondary consequence, spreads a message that usually results in disease to the rest of the body.

Why excess body fat causes insulin resistance

Two major mechanisms contribute towards weight gain. Not only do existing fat cells increase their fat content, but new fat cells are continuously being formed through a proliferation process. Individually, newly formed fat cells also start accumulating fat which collectively leads to accelerated weight-gain and the progressive enlargement of the total fat mass. In a more advanced state, this process leads to the distortion of fatty tissue, commonly referred to as cellulite.

In the past, fat cells were accredited with only two main functions, namely that of storing calories for later use and preserving body temperature via improved insulation. However, in the presence of excess body fat, fat cells also assume a new biochemical communication function by starting to manufacture various messenger molecules including ‘adipokines’ and ‘inflammatory cytokines’. These have an effect on many different tissue types and tend to interfere with the normal chemical function of the body.   For reasons not completely understood, some inflammatory cytokines disrupt insulin’s role on a cellular level when it comes to regulating blood sugar, leading to type 2 diabetes.

Adipokines, on the other hand, initiate the process of new fat cell formation called ‘adipogenesis’. In reality, by releasing adipokines and inflammatory cytokines, fat cells, in essence, become an endocrine organ which starts to function independently from the body. A vicious cycle ensues during which you become physiologically and biochemically altered, and you are virtually held hostage by your own abnormal fatty tissue.

Blocking the communication process between fat cells at a cellular level, especially when it comes to the formation of new fat cells and the development of insulin resistance, has, therefore, become a modern therapeutic focus.

Why elevated insulin levels cause weight gain

Insulin performs several different functions that may lead to the accumulation of excess body fat. Firstly, insulin regulates fat production. After a meal, when the quantity of glucose that enters the system is more than what can be used for immediate energy requirements, insulin promotes the conversion of excess sugar into fatty acids. These are subsequently grouped as larger molecules called triglycerides and transported to the fatty tissue where it is stored.

In the body, fat cells represent the ultimate energy store room. Starting life as a miniature pantry, these unique storage containers can rapidly expand in size to fulfil the role of a massive warehouse. Within the environment of fat cells, insulin fulfils the role of storeroom manager. By design, insulin’s tasks are to firstly to fill each warehouse to maximum capacity and then secondly, to keep stock levels as high as possible by actively preventing fat from leaving.

Inside a fat cell, however, another messenger molecule called ‘hormone-sensitive lipase’ (HSL) plays an opposing role to insulin. Acting as the dispatch manager of the warehouse, HSL has the sole task of releasing as much fat from the fat cell as possible so that it can be shipped off to fuel the metabolic furnace. In the presence of insulin, however, this biochemical function is overruled and fat effectively stays trapped inside fat cells. Only once insulin levels drop can HSL perform its duty by mobilising and releasing fat from the warehouse.

The bottom line is that insulin not only helps you to gain weight but when levels are chronically elevated as in the presence of insulin resistance, it also makes it more difficult for you to lose weight.

The medical consequences of insulin resistance

Doctors deal with the complications of insulin’s obesity-promoting tendency on a daily basis. Whilst insulin is the critical regulator of blood sugar control, increased insulin levels may also lead to weight-gain. In fact, these effects can be rather counterproductive when treating an overweight diabetic patient.

Various studies have confirmed the role that insulin plays in weight gain. This includes data obtained from two landmark studies; the UKPDS (United Kingdom Prospective Diabetes Study) and DCCT (Diabetes Control and Complication Trial). The most obvious example, however, can be seen in someone who develops an insulinoma, a rare tumour of the pancreas that secretes insulin. Besides developing low blood sugar, individuals with insulinomas also gain weight at an alarming rate and can become massively obese in a very short period of time.

In the presence of insulin resistance, limiting insulin-associated weight gain through an insulin sparing mechanism has, therefore, become a novel therapeutic target.

How is insulin resistance diagnosed?

In clinical practice, a combination of fasting insulin and glucose levels are used. These are calculated according to the HOMA (Homeostatic Model Assessment) or QUICKI (Quantitative insulin sensitivity check index) method.  In specialised medical research, however, a more accurate technique called the ‘hyperinsulinemic euglycemic clamp’ is used. Research has shown that results from the HOMA and QUICKI correlate reasonably well with clamping studies regarding accuracy.

Although less precise, a more simple way to predict insulin resistance is to measure your waist circumference. According to American guidelines, males with a waistline measurement of more than 102cm and females measuring more than 88cm will be significantly more inclined towards insulin resistance. European guidelines are even more stringent, with 93cm for males and 79cm for females being the upper range of normal.

How is insulin resistance linked to type 2 diabetes?

Since some of the inflammatory cytokines that fat cells start releasing disrupt insulin’s role on a cellular level when it comes to regulating blood sugar, insulin resistance is one of the leading causes of type 2 diabetes. This escalating process, however, may also fuel a vicious cycle of increased levels of insulin resistance and as a consequence, a greater requirement for insulin, thereby posing the threat of gaining even more weight. Whilst optimal glycemic control is essential to good health, weight gain is also known to accelerate some of the other disease processes associated with the metabolic syndrome, thereby potentially undermining the metabolic and cardiovascular benefits of optimal blood glucose control.

What is the link between insulin resistance and inflammation?

Excess body fat leads to the release of various inflammatory cytokines. In type 2 diabetics, insulin resistance is associated with low-grade chronic inflammation. Since this process is a known risk to develop blood clots in the presence of hardening of the arteries, it is often used to explain some of the microvascular complications that occur in type 2 diabetes. However, there is also significant evidence to suggest that even before the clinical diagnosis of type 2 diabetes is made, those with excess body fat have an increased risk of cardiovascular disease and vascular thrombosis because of low-grade inflammation.

What is the link between insulin resistance and PCOS?

Besides playing the dominant role in metabolism, insulin has a number of other hormonal effects including the regulation of normal ovarian function and influencing a number of male hormones present in females. Increased levels of insulin, as caused by insulin resistance, causes a reduction in a hormone called sex hormone-binding globulin (SHBG) in the liver. This results in abnormally high levels of male hormones in women.

What is the link between insulin resistance and stress?

Various hormones are influenced by stress, especially cortisol, which has been implicated in the development of insulin resistance.  It is also known that insulin resistance and the various inflammatory cytokines that are released by the fat cells during the process can result in far reaching biochemical consequences.  These are known to have a negative impact on brain function, leading to concentration and mental processing problems, irritability and mood disorders, including depression, sleep disorders and dementia.