Insulin Resistance, Hyperinsulinemia and Hyperglycemia

The distinction between insulin resistance and hyperinsulinemia is often unclear because these terms are frequently lumped together under “insulin resistance“, but they are separate concepts. Hyperinsulinemia (“too high insulin”) is when there is too much insulin secreted from the pancreas in response to high levels of blood sugar (hyperglycemia) and insulin resistance is where the taking in of that glucose into the cells is impaired.

Blood glucose is a tightly regulated process. A healthy person’s blood glucose is kept in the range from 3.3-5.5 mmol/L (60-100 mg/dl) but after they eat, their blood sugar rises as a result of the glucose that comes from the broken-down carbohydrate-based food. This triggers the hormone insulin to be released from the pancreas, which signals the muscle and adipose (fat) cells of the body to move the excess sugar out of the blood. What happens in insulin resistance is that the cells of the body ignore signals from insulin telling it to move glucose from broken down from digested food from the blood into the cells. When someone is insulin resistant, blood glucose stays higher than it should be for longer than it should be (hyperglycemia).

The Process of Moving Glucose Inside the Cell

A special transporter (called GLUT4) that can be thought of as a ‘taxi’ exists in muscle and fat cells and is controlled by insulin. This ‘taxi’ moves glucose from the blood and into the cells. GLUT4 ‘taxis’ are kept inside the cell until they’re needed. When ‘taxis’ are required, they go to the surface of the cell, bind with insulin and pick up their ‘passenger’ (glucose) and moves it inside the cell. Both the ‘taxi’ (GLUT4 receptor) and the insulin are also taken inside the cell and then replaced on the surface of the cell with new receptors. As long as there are GLUT4 ‘taxis’ available on the surface of the cell to transport glucose inside everything’s good, but when blood sugar is quite high, the pancreas keeps releasing insulin to bind with the GLUT4 ‘taxis’, but those ‘taxis’ may not appear fast enough on the cell surface to pick up the glucose. In this case, blood sugar remains higher then it should be for longer, a state called hyperglycemia. When there are insufficient receptors to move glucose into the cell, this is called insulin resistance. It may be temporary, as in the example above, or may be long-term. If it is temporary, the rise in blood sugar (hyperglycemia) is short but if the receptors don’t respond properly long-term, then blood sugar remains higher for a longer period of time, until the ones that do work can bring the glucose inside. In one case, the blood sugar may be quite high for a short time or may be moderately high for a long time. In both cases, the body is exposed to higher blood sugar than it should be, and this causes damage to the body. It isn’t known whether insulin resistance comes first or hyperinsulinemia does. It is believed that it may be different depending on the person.

What Triggers Hyperinsulinemia?

It is known that excessive carbohydrate intake can trigger hyperglycemia, as well as hyperinsulinemia. Eating lots of fruit, for example or foods that contain fructose (fruit sugar) will cause the body to move that into the body first in order to get it to the liver, before it deals with glucose. This causes glucose levels in the blood to rise, resulting in both hyperglycemia and hyperinsulinemia. Lots of processed foods contain high fructose corn syrup (HFCS) which contributes to problems with high blood sugar and hyperinsulinemia.

There are other things that can also trigger hyperglycemia and hyperinsulinemia include certain medications (like corticosteroids and anti-psychotic medication) and even stress. Stress causes the hormone cortisol to rise, which is a natural corticosteroid. It is thought that long-term stress may lead to hyperinsulinemia, which increases appetite by affecting neuropeptide Y expression. This may explain why people eat more when they’re stressed and are very often drawn to carbohydrate-based foods that are quickly broken down for energy.

Diseases Associated with Hyperinsulinemia

It is well known that hyperglycemia that occurs with Type 2 Diabetes contributes to problems with the eyes, kidneys and nerves of the extremities, especially the feet and toes. Less known are the diseases and metabolic problems that can occur due to hyperinsulinemia.

Hyperinsulinemia has a well-establish association to the development of Type 2 Diabetes and Gestational Diabetes (the Diabetes of pregnancy), but also to Metabolic Syndrome (MetS).

Metabolic Syndrome (MetS) is a cluster of symptoms that together put people at increased risk for cardiovascular disease, including heart attack and stroke.

These symptoms of MetS include having 3 or more of the following;

  1. Abdominal obesity (i.e. belly fat), specifically, a waist size of more than 40 inches (102 cm) in men and more than 35 inches (89 cm) in women
  2. Fasting blood glucose levels of 100 mg/dL (5.5 mmol/L) or above
  3. Blood pressure of 130/85 mm/Hg or above
  4. Blood triglycerides levels of 150 mg/dL (1.70 mmol/L) or higher
  5. High-density lipoprotein (HDL) cholesterol levels of 40 mg/dL (1.03 mmol/L) or less for men and 50 mg/dL (1.3 mmol/L) or less for women

Hyperinsulinemia is also an independent risk factor for obesity, osteoarthritis, certain types of cancer including breast and colon/rectum, Alzheimer’s Disease and other forms of dementia[1], erectile dysfunction[2] and polycystic ovarian syndrome (PCOS)[3].

The damage associated with hyperinsulinemia is due to the continuous action of insulin in the affected tissues[4].

Risk factors for developing insulin resistance include a family history of Type 2 Diabetes, in utero exposure to Gestational Diabetes (i.e. an unborn child whose mother had Gestational Diabetes), abdominal obesity (fat around the middle) and detection of hyperinsulinemia.  Assessors of insulin resistance using blood tests such as the Homeostatic Model Assessment (HOMA2-IR) test which estimates β-cell function and insulin resistance (IR) from simultaneous fasting blood glucose and fasting insulin or fasting blood glucose and fasting C-peptide[1]. As well, incorporation of some forms of exercise including resistance training may lower insulin resistance in the muscle cells and weight loss – even when people are not very overweight can increase uptake of glucose, due to lowered insulin resistance of the liver.

Detection of hyperinsulinemia can occur using an Oral Glucose Sensitivity Index (OGIS), which is similar to a 2-hr Oral Glucose Tolerance Test (2-hr OGTT) which is a test where a fasting person drinks a known amount of glucose and their blood sugar is measured before the test starts (baseline, while fasting) and at 2 hours. In the OGIS, both blood glucose and blood insulin levels are measured at baseline (fasting), at 120 minutes and at 180 minutes [5].

Glucose and insulin response patterns that result after people take oral glucose can also be used to determine hyperinsulinemia status. Between 1970 and 1990, Dr. Joseph R. Kraft collected data from almost 15,000 people which showed five main glucose and insulin response patterns; with one being the normal response. Kraft’s methodology was to measure both glucose and insulin response over a 5-hour period, noting the size of both the glucose and insulin peaks, as well as the rate that it took the peaks to come back down to where it started from. Kraft concluded that a 3-hour oral glucose tolerance test with both glucose and insulin measured at baseline (fasting), 30, 60 120 and 180 minutes was as accurate as a 5-hour test. Most striking about the original study and recent re-analysis of this data found that up to 75% of people with normal glucose tolerance have carrying degrees of hyperinsulinemia [9]. You can read more about that in this recent article.

Hyperinsulinemia and insulin resistance together are the essence of carbohydrate intolerance; the varying degrees to which people can tolerate carbohydrate without their blood sugar spiking. This is not unlike other food intolerance such lactose intolerance or gluten intolerance which reflect the body’s inability to handle specific types of carbohydrate in large quantities.

Some final thoughts…

Insulin resistance and hyperinsulinemia are present long before a diagnosis of pre-diabetes and are now are considered an entirely separate stage in the development of the disease (you can read more about that here). A recent study reported that abnormal blood sugar regulation precedes a diagnosis of Type 2 Diabetes by at least 20 years [6] which means that long before blood sugar becomes abnormal, the progression to Type 2 Diabetes has already begun. Knowing how to recognize the symptoms of insulin resistance and hyperinsulinemia and to have them measured or estimated, as well as to detect the abnormal spike in blood glucose that often occurs 30 to 60 minutes after eating carbohydrate-based food is essential to avoiding progression to Type 2 Diabetes as well as the complications associated with hyperglycemia and hyperinsulinemia.

If you would like my help in lowering your risk to developing Type 2 Diabetes and the chronic disease risks associated with hyperinsulinemia or in reversing their symptoms, please send me a note using the Contact Me form on the tab above. I provide both in-person consultations as well as by Distance Consultation,using Skype and phone.

To your good health!

Joy

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References

  1. Crofts, C., Understanding and Diagnosing Hyperinsulinemia. 2015, AUT University: Auckland, New Zealand. p. 205.
  2. Knoblovits P, C.P., Valzacci GJR,, Erectile Dysfunction, Obesity, Insulin Resistance, and Their Relationship With Testosterone Levels in Eugonadal Patients in an Andrology Clinic Setting. Journal of Andrology, 2010. 31(3): p. 263-270.
  3. Mather KJ, K.F., Corenblum B, Hyperinsulinemia in polycystic ovary syndrome correlates with increased cardiovascular risk independent of obesity. Fertility and Sterility, 2000. 73(1): p. 150-156.
  4. Crofts CAP, Z.C., Wheldon MC, et al, Hyperinsulinemia: a unifying theory of chronic disease? Diabesity, 2015. 1(4): p. 34-43.
  5. Crofts, C., et al., Identifying hyperinsulinaemia in the absence of impaired glucose tolerance: An examination of the Kraft database. Diabetes Res Clin Pract, 2016. 118: p. 50-7.
  6. Sagesaka H, S.Y., Someya Y, et al, Type 2 Diabetes: When Does It Start? Journal of the Endocrine Society, 2018. 2(5): p. 476-484.

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Author: BBDN

Joy Y Kiddie MSc., RD - I'm a Registered Dietitian in private practice in British Columbia, Canada that provides services in-person in my Coquitlam office, as well as by Distance Consultation (using Skype / telephone).