Insulin is a hormone that is produced by the beta cells of the pancreas. These cells are scattered throughout the pancreas in small clusters known as the islets of Langerhans. The insulin produced is released into the blood stream and travels throughout the body. Insulin is an essential hormone that has many actions within the body. Most actions of insulin are directed at metabolism (control) of carbohydrates (sugars and starches), lipids (fats), and proteins. Insulin also regulates the functions of the body's cells, including their growth. Insulin is critical for the body's use of glucose as energy.
Insulin resistance (IR) is a condition in which the body's cells become resistant to the effects of insulin. That is, the normal response to a given amount of insulin is reduced. As a result, higher levels of insulin are needed in order for insulin to have its proper effects. So, the pancreas compensates by trying to produce more insulin. This resistance occurs in response to the body's own insulin (endogenous) or when insulin is administered by injection (exogenous).
With insulin resistance, the pancreas produces more and more insulin until the pancreas can no longer produce sufficient insulin for the body's demands, then blood sugar rises. Insulin resistance is a risk factor for development of diabetes and heart disease.
What is the relationship between insulin resistance and diabetes?
Type 2 diabetes mellitus (T2D) is the type of diabetes that occurs later in life or with obesity at any age. Insulin resistance precedes the development of type 2 diabetes, sometimes by years. In individuals who will ultimately develop type 2 diabetes, it has been shown that blood glucose and insulin levels are normal for many years, until at some point in time, insulin resistance develops.
At this point, high insulin levels are often associated with central obesity, cholesterol abnormalities, and/or high blood pressure (hypertension). When these disease processes occur together, it is called the metabolic syndrome.
One action of insulin is to cause the body's cells (particularly the muscle and fat) to remove and use glucose from the blood. This is one way by which insulin controls the level of glucose in blood. Insulin has this effect on the cells by binding to insulin receptors on the surface of the cells. You can think of it as insulin "knocking on the doors" of muscle and fat cells. The cells hear the knock, open up, and let glucose in to be used. With insulin resistance, the muscles don't hear the knock (they are resistant). So, the pancreas is notified that it needs to make more insulin, which increases the level of insulin in the blood and causes a louder knock.
The resistance of the cells continues to increase over time. As long as the pancreas is able to produce enough insulin to overcome this resistance, blood glucose levels remain normal. When the pancreas can no longer produce enough insulin, the blood glucose levels begin to rise. Initially, this happens after meals - when glucose levels are at their highest and more insulin is needed - but eventually while fasting too (for example, upon waking in the morning). When blood sugar rises abnormally above certain levels, type 2 diabetes is present.
What medical conditions are associated with insulin resistance?
While the metabolic syndrome links insulin resistance with abdominal obesity, elevated cholesterol, and high blood pressure; several medical other conditions are specifically associated with insulin resistance. Insulin resistance may contribute to some of the conditions listed.
Type 2 Diabetes
Overt diabetes may be the first sign that insulin resistance is present. Insulin resistance can be noted long before type 2 diabetes develops. Individuals reluctant or unable to see a health care practitioner regularly often seek medical attention when they have already developed type 2 diabetes and insulin resistance.
Fatty liver is strongly associated with insulin resistance. Accumulation of fat in the liver is a manifestation of the disordered control of lipids that occurs with insulin resistance. Fatty liver associated with insulin resistance may be mild or severe. Newer evidence suggests that fatty liver may even lead to cirrhosis of the liver and, possibly, liver cancer.
Arteriosclerosis (also known as atherosclerosis) is a process of progressive thickening and hardening of the walls of medium-sized and large arteries. Arteriosclerosis is responsible for:
- Coronary artery disease (leading to angina and heart attack)
- Peripheral vascular disease
Other risk factors for arteriosclerosis include:
- High levels of "bad" (LDL) cholesterol
- High blood pressure (hypertension)
- Diabetes mellitus from any cause
- Family history of arteriosclerosis
Skin lesions include increased skin tags and a condition called acanthosis nigricans (AN). Acanthosis nigricans is a darkening and thickening of the skin, especially in folds such as the neck, under the arms, and in the groin. This condition is directly related to the insulin resistance, though the exact mechanism is not clear.
- Acanthosis nigricans is a cosmetic condition strongly associated with insulin resistance in which the skin darkens and thickens in creased areas (for example, the neck, ar pits, and groin).
- Skin tags are occur more frequently in patients with insulin resistance. A skin tag is a common, benign condition where a bit of skin projects from the surrounding skin. Skin tags vary significantly in appearance. A skin tag may appear smooth or irregular, flesh colored or darker than surrounding skin, and either be simply raised above surrounding skin or attached by a stalk (peduncle) so that it hangs from the skin.
Polycystic ovary syndrome is a common hormonal problem which affects menstruating women. It is associated with irregular periods or no periods at all (amenorrhea), obesity, and increased body hair in a male pattern of distribution (called hirsutism; for example, moustache, sideburns, beard, mid-chest, and central belly hair).
Hyperandrogenism: With PCOS, the ovaries can produce high levels of the hormone testosterone. This high testosterone level can be seen with insulin resistance and may play a role in causing PCOS. Why this association occurs is unclear, but it appears that the insulin resistance somehow causes abnormal ovarian hormone production.
High levels of circulating insulin can affect growth. While insulin's effects on glucose metabolism may be impaired, its effects on other mechanisms may remain intact (or at least less impaired). Insulin is an anabolic hormone which promotes growth. Patients may actually grow larger with a noticeable coarsening of features. Children with open growth plates in their bones may actually grow faster than their peers. However, neither children nor adults with insulin resistance become taller than predicted by their familial growth pattern. Indeed, most adults simply appear larger with coarser features. The increased incidence of skin tags mentioned earlier may occur through this mechanism too.