Insulin Resistance

What is it?

Insulin is a hormone produced by the beta cells in the pancreas. Small amounts of insulin are normally released into the bloodstream after each meal and help transport glucose into the body’s cells where it is needed for energy production. Insulin resistance is a decreased ability of the body to respond to the effects of insulin especially by muscle and adipose (fat) tissues. Since cells must have glucose to survive, the body compensates for insulin resistance by producing additional amounts of the hormone. This results in a state of hyperinsulinaemia in the blood and over-stimulation of some tissues that have remained insulin sensitive. Over time, this process causes an imbalance in the relationship between glucose and insulin and can have adverse effects in the body.  

Hyperinsulinaemia and insulin resistance can affect the proportion of the body’s lipids, significantly increasing the amount of triglycerides and sdLDLs (small dense lipoproteins) in the blood and decreasing the amount of HDL (high density lipoprotein) cholesterol level, (the “good cholesterol”). It may also increase a person’s risk of developing a blood clot, cause inflammatory changes, and increase a person’s sodium retention, which can lead to increased blood pressure. It is also a vascular risk factor, increasing the likelihood of disease in arteries.

Insulin resistance is not a disease or specific diagnosis, but it has been associated with conditions such as cardiovascular disease (CVD), hypertension, polycystic ovarian syndrome (PCOS), type 2 diabetes, obesity and non-alcoholic fatty liver disease. Some researchers also believe that there may be a link between insulin resistance and some forms of cancer. The mechanisms of these associations, however, are not well understood. It is important to remember that many of the people who have these conditions do not have insulin resistance and, likewise, many of the people who have insulin resistance will never develop these conditions. These are just patterns of association that have emerged. They are frequently seen together and it is thought that insulin resistance may contribute to their development and exacerbate them when it is present.

Metabolic syndrome and insulin resistance syndrome are two terms that have been used to characterize some of the abnormalities associated with insulin resistance and to recognize them as risk factors for future disease. Although both terms are often used interchangeably, metabolic syndrome is more of a subset of the insulin resistance syndrome. It is a worldwide effort to identify patients who are primarily obese and sedentary and who are beginning to experience alterations in lipid levels and impaired glucose processing. The focus is on educating them about their increased risk of developing CVD and/or type 2 diabetes and on working with them to lower that risk through lifestyle changes. Since obesity and lack of exercise are known to exacerbate insulin resistance and exercise is known to increase the body’s sensitivity to insulin, identifying and treating those with metabolic syndrome also improves their insulin resistance. The insulin resistance syndrome term is broader. It’s intent is to define and catalogue the abnormalities and conditions that have been associated with insulin resistance and hyperinsulinaemia.

The cause of insulin resistance is not fully understood. It is thought to be due partly to genetic factors, including ethnicity, and partly to lifestyle, such as excessive caloric intake and inadequate exercise. Most patients with insulin resistance do not have any symptoms and they do not realize that this process is taking place in their bodies. In most cases, the body is able to keep pace with the need for extra insulin production, and the effects of it on the body are subtle and years in the making. If or when the body’s insulin production fails to keep up with demand, then hyperglycaemia will occur. Over time, hyperglycaemia can progress and become type 2 diabetes, which can damage body organs. At this stage symptoms may be present.

Tests

There is no one test that can directly detect insulin resistance. Instead, a doctor will look at a patient’s entire clinical picture and may suspect that the patient has insulin resistance if he has increased blood glucose levels, increased levels of triglycerides and LDL cholesterol, and decreased concentrations of HDL cholesterol. Laboratory tests most likely to be ordered include:

  • Glucose. This is usually performed fasting but, in some cases, a doctor may also request a GTT (glucose tolerance test – two glucose tests that are taken before and 120 minutes after a glucose challenge). The goal of glucose testing is to determine whether a patient has an impaired response to glucose i.e. whether the blood glucose level climbs higher than it should under normal circumstances.
  • Lipid profile. This measures the HDL, LDL, triglycerides, and total cholesterol. If the triglycerides are significantly elevated, a DLDL (direct measurement of the LDL) may need to be done.

Other laboratory tests that may be used to help evaluate insulin resistance and provide additional information include:

  • Insulin. The fasting insulin test is variable, but insulin levels will usually be elevated in those with significant insulin resistance.
  • hs-CRP. This is a measure of low levels of inflammation that may be done as part of an evaluation of cardiac risk. It may be increased with insulin resistance. Mild inflammation is a feature of metabolic syndrome.
  • sdLDL. This is a measurement of the number of small dense low-density lipoprotein molecules a patient has. This test is not ordered frequently but may be measured as part of a lipoprotein subfractions test.
  • Insulin tolerance test (ITT). Not widely used but is one method for determining insulin sensitivity (or resistance), especially in obese individuals and those with PCOS. This test involves an IV-infusion of insulin, with subsequent measurements of glucose and insulin levels.

Specific insulin suppression tests may also be requested in a research setting to study insulin resistance but are not generally used in a clinical setting. An intravenous glucose tolerance test can be carried out where the glucose load is given into a vein rather than by mouth but again this test tends to be used for research purposes only rather than in a clinical setting.

Treatment

Treatment of insulin resistance primarily involves changes in diet and lifestyle. This life style and dietary change will include losing excess weight, taking regular amounts of moderate-intensity physical activity, and increasing dietary fibre to lower blood insulin levels and increase the body’s sensitivity to it. Weight loss and exercise can:

  • Decrease blood pressure levels
  • Increase insulin sensitivity (ie decrease insulin resistance)
  • Decrease triglyceride and LDL cholesterol levels
  • Raise HDL cholesterol levels (with regular exercise)  

Patients who are identified by their doctors as having insulin resistance should work with their doctor and with other medical professionals to develop an individualised treatment plan and to monitor its effectiveness. Drug treatments may also be necessary to control any existing, underlying, associated conditions and diseases.