Introduction to Insulin, Insulin Resistance (IR) and Metabolic Syndrome

By Catherine Haug; moved and updated Mar 30, 2021

I originally wrote this article for my old website in Jan 2007, then updated/reorganized it in Feb and Aug 2007 (using iWeb software that is no longer available), so I have copied it here. See Diet and Health Menu under “Insulin, Insulin Resistance, and Metabolic Syndrome” for list of other articles about Insulin Resistance (some still need to be moved to Cat’s Kitchen).

Insulin is an important, ancient hormone; it:

  • signals the processes that move glucose into cells for energy production;
  • causes any excess sugar to be stored in adipose (fat) cells as fat;
  • suppresses glucagons and growth hormones, which regulate the burning of fat (and stored fat) and rate of muscle development, respectively.

Thus insulin acts as a double-edged sword in response to excess dietary carbs:  insulin promotes storage of the excess carbohydrates as body fat, and then wards off the body’s ability to lose that fat. (7) For more, read on …

Type-2 Diabetes and Blood Glucose Levels

Added in April 2021 update of this article:  The “rules” for diagnosis changed in 1997, lowering the fasting glucose levels, as follows (1):

  • Fasting glucose level less than 110 mg/dL is considered normal
  • Fasting glucose level between 110 and 126 mg/dL indicates impaired glucose tolerance (insulin resistance)
  • Fasting glucose level at or above 126 mg/dL indicates diabetes.

Prior to that change, the number for diabetes diagnosis was 140 mg/dL.

Insulin

Insulin’s major role is to control the rate of aging. (2)  It does this by regulating sugar and fat metabolism.  Studies of centenarians reveal there is little they have in common; for example, some never smoke while others are life-long smokers.  Yet there are three things — three metabolic indicators — that are relatively consistent among centenarians:

  • low serum glucose;
  • low serum triglycerides;
  • low serum insulin.

The common denominator for all three of these indicators is insulin, because it regulates the other two. Cells of centenarians are consistently sensitive to insulin; insulin sensitivity is one of the most important markers of lifespan. (6) 

What is Insulin Resistance?

Move this, where: 2018 update: Functional Medicine practitioners believe that Insulin Resistance is result of problems in the mitochondria, the cells’ batteries. For more, see Mercola article (15).

Original article:

Insulin resistance (IR) is much in the news lately.  It is characterized by two metabolic problems; both of which occur when the body’s cells become insensitive to insulin:

  • Inability of cells to respond to insulin, thus depriving them of needed glucose for energy production, despite the presence of adequate glucose in the blood stream; (9)
  • Inability of muscle cells to produce glycogen from excess sugar; instead, the excess sugar is routed to the liver where it is converted to fat, which is then routed through the blood for storage in visceral fat (adipose tissue, primarily around the body’s middle), or accumulates in the liver (fatty liver). (8)

No one really knows what causes the insensitivity to insulin that starts this ball rolling, but there are many theories, and perhaps many causes.  Neither is it known wether the problem is with the insulin receptors on the cell membrane, or with signaling molecules within the cell, or in the mitochondria where glucose is either burned as fuel or converted to glycogen for storage.  

The end result, however, is known.  Both serum insulin and serum glucose levels rise, eventually to toxic levels, and at the same time, blood levels of triglycerides and LDL cholesterol rise, and HDL (the ‘good’ cholesterol) levels fall.  And that is when a complex of symptoms begin to appear.  These include: (3)  [See section on symptoms, below, for more specific symptoms of insulin resistance.]

  • hyperinsulinemia (high blood insulin),
  • hypertension (high blood pressure), 
  • atheroscleroisis (hardening of arteries due to plaque formation), 
  • angina (chest pain).
  • coronary heart disease (CHD), 
  • obesity, and 
  • type-II diabetes (hyperglycemia, or high blood sugar).

Back in the 1920s when these symptoms began to appear at a greater rate than had been previously observed, doctors recognized them as related.  But as time went forward, the philosophy of allopathic medicine ceased to look at the ailing body as a whole, and began to focus on the symptoms separately, as though they were separate diseases.  This situation persists to this day.  Does the following scenario sound familiar to you?

  • At your annual checkup, your doctor detects high blood pressure and prescribe a pill; 
  • He detects “abnormal” cholesterol and puts you on another pill;
  • If you’re a woman, you might complain of hormone imbalances, or you might go for a bone scan, and be told that you have osteoporosis.  He then puts you on more pills.
  • You complain of angina so your doctor puts you through a treadmill test and then recommends bypass surgery;
  • If you decide to put that off, you might have a myocardial infarction (MI; also known as heart attack), and then he insists on bypass surgery;
  • He tells you that you are obese and admonishes you to lose weight (as if you hadn’t already been trying to no avail, and finally gave up); 
  • The doc detects high blood sugar and then prescribes yet another pill–or insulin injections.  
  • If you have an enlightened doctor, he may do an insulin challenge test, and thus discover the hyperinsulinemia (high blood insulin level) that underlies all the other symptoms.  And then prescribe a pill.

These doctors are not interested in healing the patient, but rather simply in controlling the progress of the symptoms (making a lot of money for themselves and the drug companies in the process).  This is a very sad state of affairs.  

The good news is that the situation is changing.  An increasing number of health researchers recognize the relationship of all these symptoms to insulin resistance (IR), and lump all these disorders together under the name of Metabolic Syndrome, AKA “Syndrome-X.”  They recognize that all these symptoms, each a serious killer in its own right, can be traced back to IR. (3)  

And that puts them in a position, not just to control the progression of this disease, but also to help you reverse it. 

Symptoms of Insulin Resistance

Note: in addition to the symptoms listed below, I have recently discovered the connection between adrenal fatigue, adrenal exhaustion and insulin resistance. See also my article on Cortisol & Adrenal Fatigue.

The following symptoms occur because there is either too little glucose (hypoglycemia) or too much glucose (hyperglycemia) in the blood, and because insulin controls other hormones that affect the cellular function responsible for the symptom. For more, refer to healingdaily.com/detoxification-diet/insulin.htm: (6) 

  • Fatigue;
  • Brain fogginess (can’t focus, poor memory, loss of creativity);
  • Low blood sugar (hypoglycemia):  agitated, jittery, moody;
  • High blood sugar (hyperglycemia), later in the progression of IR;
  • Intestinal bloating;
  • Sleepiness after a meal;
  • Weight gain, obesity;
  • Increased serum triglycerides (TG);
  • Increased blood pressure;
  • Depression.

Another source (Women’s International) also lists warning signs of insulin resistance; unfortunately, that page is no longer available.

  • frequent thirst
  • frequent urination
  • excessive hunger
  • unexplained drowsiness or feeling tired most of the time, especially after eating
  • inability to concentrate
  • decreased endurance during physical exertion and exercise
  • inflammation
  • low HDL, the “good” cholesterol
  • skin tags or dark discoloration (acanthosis nigricans) around the neck, groin or armpits.

In addition to the symptoms listed above are the less apparent (but no less important):

  • increased deaths from all causes (3);
  • osteoporosis (2);
  • female reproductive disorders (3); 
  • anorexia/bulemia (3);
  • non-alcoholic fatty liver disease (3);
  • non-alcoholic steatohepatitis (3);
  • POS (polycystic ovary syndrome) (3);
  • gestational diabetes mellitus (3); and 
  • certain cancers. (3)

My symptoms, over the years, include:

  • early on (in my 20s), I had hypo-glycemia (low blood sugar), but back then (early 1970s) no docs knew what that meant, nor how to treat it. I still experience it if I’m late in getting a meal.
  • fatigue; 
  • brain fogginess (can’t focus, poor memory, loss of creativity);
  • low blood sugar (hypoglycemia):  agitated, jittery, moody;
  • intestinal bloating;
  • weight gain, obesity (as I got into my 50s);
  • frequent thirst;
  • frequent urination;
  • excessive hunger;
  • unexplained drowsiness or feeling tired most of the time, especially after eating;
  • decreased endurance during physical exertion and exercise;
  • inflammation;
  • non-alcoholic fatty liver disease.

I note that in 2015, I started taking Pure Encapsulations brand of myo-inositol supplement (a B-vitamin) at the recommendation of my naturopath, taking 1/4 tsp/day. It’s positive effect was amazing! I lost weight, had more energy, and many of the symptoms listed above went away. I continue to take myo-inositol at a higher dose (1/2 tsp/day), to help my liver and keep things in check. See also my article Choline, Inositol, and Insulin Resistance for more about this.

NOTE: I tried switching to a less expensive brand (NOW or Jarrow), but these didn’t help as much so I went back to Pure Encapsulations. 

Testing for Blood Sugar Level

Fasting blood sugar has been the main test for type-2 diabetes, with generally accepted ranges as follows: 

  • Normal: any level lower than 100 mg/dL
  • Pre-Diabetic: 100 – 125 mg/dL
  • Diabetic: any level greater than 125 mg/dL

However, a 22-year study published in 1999 (16) indicates any reading greater than 85 is “diabetic”. Recommendations: Keep your blood sugar in the range of 70-85 mg/dL – and don’t allow after-meal glucose levels to spike higher than 40 mg/dL.

Type-2 Diabetes is really just an advanced stage of Insulin Resistance, for which anything above 85 mg/dL blood sugar level has long been the indicator, so this should come as no surprise.

Fasting blood sugar level is not the only test that should be run. In fact, fasting blood insulin may be even more important, especially if used to determine ratio between the two levels (from same blood sample).  My naturopath explained this: If your body’s cells run out of fuel during the night while sleeping, the body makes more.

A1C test is becoming more popular and common Need more

See below for more detail.

Testing for Blood Insulin Level

Your doctor can order a simple test to measure your insulin.  Some doctors just request a measure of fasting insulin (blood insulin after a 12-hour fast).  While this has some value, insulin resistance is not the only cause of elevated fasting insulin.  Therefore, a better test is the insulin challenge test.  This is similar to the Glucose Tolerance Test used to diagnose diabetes, but instead of just measuring glucose levels, both glucose and insulin levels are measured after the 12-hour fast, and then for 3 – 4 hours after a high-carb meal (post prandial).

Fasting insulin above 15 uIU/ml is often used as an indicator of insulin resistance but according to Dr Mercola and Dynamic Integration Centers, a level above 10 is cause for concern; a level above 15 is considered hyperinsulinemia.  Ideally, fasting insulin should be below 5. (2, 12, 13)  Whole Health Source says that fasting insulin between 2 and 6 uIU/ml is ideal. Wikipedia says that levels above 60 pmol/ml (8.4 uIU/ml) indicates hyperinsulinemia.

Note, insulin levels can be reported as uIU/ml or pmol/ml (there may be others as well). When comparing values, it is important to have the same type of measurement. To convert from pmol/ml to uIU/ml, divide by 7.175. Thus 60 pmol/ml equates to 8.4 uIU/ml.

Measured Blood Sugar and Insulin Levels, Ratios; and insulin-challenge test

Fasting Levels and ratios:

Simple glucose:insulin ratio (from Mercola): the ratio of glucose to insulin (fasting) is an even more important indicator of problems. It should be less than 10:1; any value above that is cause for concern. (11) 

For example, my ratios:

  • Mar 2011:  fasting BS in Mar, 2011 was 111; my fasting insulin was 12. My glucose:insulin ratio is 111:12 or 9:1. I’m below the threshold, but just barely.
  • Mar 2013: fasting glucose = 100 mg/dL; fasting insulin = 20.8 uIU/ml; ratio = 100:20.8 or 5:1. Note that I started on a ketogenic eating plan during 2013.
  • Jan 2014 is similar, with ratio – 107:20.3 or 5:1. Much better than 2011, although both levels are above optimal in both years. This could be result of liver working to correct too-low glucose during night.
  • Mar 2018: fasting glucose =  112 mg/dl; fasting insulin = 23.1 mcIU/ml (not uIU/ml, but both mc and u mean micro); ratio = 4.8:1, which is an improvement, but the insulin is still too high (should be about 8.6 according to Mercola).
  • Mar 2019: fasting glucose = 106 mg/dL; fasting insulin = 19.8 mcIU/ml; ratio is 5.3:1, slightly higher than last year. If I use the fasting total insulin of 20.2, I get a ratio of 5.2:1.

HOMA-IR (from Dr. Tom O’Bryan interview with Dr. Brian Mowll). Optimal range is 1 – 1.5; anything over 2 is considered insulin resistance. The US formula is:

(fasting insulin) x (fasting glucose) / 405

There are also calculators online; search “HOMA-IR calculator”. For example: thebloodcode.com/homa-ir-calculator/ .There are other sites with the calculator, but be sure to pick one from the US, not the UK or other countries if you live in the US. The MD Calc link adds the following caution: “The HOMA-IR score should not be used in patients on insulin, and studies have questioned its accuracy in those with impaired glucose tolerance, normal BMI, the elderly, and others.”

For example, my HOMA-IR scores (from the data above): 

  • Mar 2011:  fasting insulin = 12, fasting glucose = 111; HOMA-IR =  3.3
  • Mar 2013: fasting insulin = 20.8, fasting glucose = 100; HOMA-IR = 5.1
  • Jan 2014: fasting insulin = 20.3, fasting glucose = 107; HOMA-IR = 5.4
  • Mar 2018: fasting insulin = 23.1, fasting glucose = 112; HOMA-IR = 6.4

Clearly, it gets worse every year, even though I switched to Ketogenic eating plan in 2013. However, my ND suggests this could be result of liver working to correct too-low glucose during night.

One hour after a meal, your insulin will be high, because it is needed to get the sugars from your meal into your cells.  Two hours after a meal, your insulin should be declining, and should continue to decline back to near fasting levels, until your next meal.

But if your fasting insulin is high, insulin resistance is a possible cause.  

Post-Prandial Insulin (2 hours after a meal):

Elevated post-prandial insulin is an even more accurate indicator of insulin resistance. Here is a sample of results from my own insulin challenge test in 2003, indicating hyperinsulinemia (elevated blood insulin) and Insulin Resistance, but diabetes is not yet indicated (glucose levels are within normal ranges).  These are my own test results from 2003:

(saved as InsulinChallengeTest_table2.jpg and InsulinChallengeTest_graph2.jpg)

Reducing serum insulin levels

See How to Live Longer: 11 Ways to Reduce Insulin Levels.

Metabolic Syndrome:  What Happens When Insulin Sensitivity Goes Awry 

NOTE: Many people equate hyperinsulinemia with Metabolic syndrome; while elevated insulin is one of the features of Metabolic syndrome, there can be other causes of elevated insulin.

When cells become insulin resistant, but those same cells still have a need for a particular nutrient regulated by insulin, the pancreas produces more insulin.  This interferes with the proper metabolism of glucose and fats at the cellular level, which shows up as an abnormal lipid profile, a risk factor for atherosclerosis.  In particular:

  • High Density Lipoprotein (HDL):  Elevated insulin lowers serum HDL levels (HDL carries excess cholesterol back to the liver for recycling).  
  • Low Density Lipoprotein (LDL):  Elevated blood insulin raises serum LDL (carries cholesterol to peripheral cells), promoting the processes that favor creation of relatively small, dense LDL (as opposed to large, buoyant LDL), which can more readily enter the arterial endothelium and cause atherosclerotic lesions. Conversely, when HDL is raised, TGs are lowered, favoring the creation of the larger LDL particles. (4)
  • Triglycerides (TG):  Elevated insulin is involved in raising serum TGs in several ways.  Excess serum glucose, which results from elevated insulin, is converted to triglycerides in the liver, showing up as elevated serum TGs en route to be stored in the adipose cells.  
  • Insulin also regulates lipoprotein lipase (LPL) enzyme synthesis.  LPL is responsible for freeing fatty acids from the triglycerides in VLDL and IDL.  Thus, as insulin levels rise, LPL levels decline, and serum TGs rises. (4)
  •   High levels of serum TGs have been associated with an increase in atherosclerotic lesions.

Insulin and T3 (thyroid hormone) increase the binding of LDL to receptors in the liver, which in turn increases production of VLDL (very low density lipoprotein, measured as TGs in a lipid panel). (1)  These effects may be mediated through the regulation of Apo B degradation.  This may explain the high cholesterol levels in the blood and increased risk of atherosclerosis seen with uncontrolled diabetes or hypothyroidism. (4)

Insulin resistance also:

  • Increases blood pressure (hypertension)
  • Leads to Coronary Heart Disease (CHD)
  • Increases inflammation and  oxidative damage to arterial walls; (1) 
  • Increases the formation of blood clots; (1)  
  • Upsets sex hormone balance.  Elevated insulin often correlates with decreased DHEA production.  In a preliminary study, one research group found that DHEA reduced abdominal fat and improved insulin sensitivity index, but noted that larger studies would be needed to verify these findings in patient groups that are fully representative of the population at risk. They conclude that “DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.” (5)5
  • Impairs thyroid function.  When thyroid cells are insulin resistant, the conversion of T4 to T3 hormone is slowed down, or stopped altogether, leading to problems associated with hypothyroidism (low thyroid), including obesity; (2)
  • Impairs sugar metabolism, eventually leading to high blood sugar (diabetes).  Excess sugar in the blood tends to “stick” to proteins in the blood, such as to the protein component of blood lipoproteins (LDL, HDL), in a process known as glycation, which is a major factor in atherosclerosis and heart attacks. (1)   Refer to The Glycation Hypothesis of Atherosclerosis for more on this subject. Move link to References
  • Impairs magnesium and sodium uptake by muscle cells, resulting in arterial constriction (as magnesium is needed for relaxation of arterial muscles is excreted in the urine) and water retention (as sodium builds up in the blood); ultimately leading to high blood pressure. (1)
  • Impairs calcium uptake by bone cells, leading to osteoporosis, as the needed calcium is instead secreted in the urine, formed into kidney stones, or incorporated into arterial plaque. (2)  

RECAP

The hormone insulin is responsible for regulating, either directly or indirectly, most anabolic and catabolic activities at the cellular level, which impact the rate of aging.  The most well-known of these is the regulation of blood sugar.  This is much in the news of late because of an epidemic disorder known as Insulin Resistance (Syndrome-X or Metabolic Syndrome), characterized by the following problems:

  • insulin resistance (IR)
  • hypertension (high blood pressure)
  • abnormalities of blood clotting
  • abnormal lipid panel (low HDL, high LDL, high triglycerides)

IR impacts many hormonal activities including insulin, thyroid, DHEA and sex hormones, and increases atherosclerotic plaque.

Go to:

References and Sources

Verify and update all links as needed

  1. yourhealthbase.com/diabetes.htm (not secure)
  2. articles.mercola.com/sites/articles/archive/2001/07/14/insulin-part-one.aspx, www.mercola.com/2001/jul/14/insulin2.htm  
  3. www.power-surge.com/educate/holt_syndromex.htm
  4. web.indstate.edu/thcme/mwking/lipoproteins.html
  5. www.medscape.com/viewarticle/493389?src=mp
  6. www.healingdaily.com/detoxification-diet/insulin.htm
  7. v.mercola.com/blogs/public_blog/Why-Americans-Keep-Getting-Fatter-22958.aspx
  8. http://articles.mercola.com/sites/articles/archive/2007/07/18/insulin-resistance-not-belly-fat-to-blame-for-metabolic-syndrome.aspx and Proceedings of the National Academy of Sciences July 18, 2007
  9. http://health.howstuffworks.com/diabetes2.htm
  10. www.mercola.com/2004/jun/5/obese_brains.htm
  11. articles.mercola.com/sites/articles/archive/2011/03/28/the-stealth-drug-cause-of-diabetes.aspx 
  12. www.newhopehealthcenter.com/dynamic_integration/Biochemistry/bloodtests.html 
  13. http://drbenkim.com/articles-bloodsugar.html 
  14. womensinternational.com/connections/insulin.html
  15. articles.mercola.com/sites/articles/archive/2018/04/15/pqq-berberine-mitochondrial-enhancers.aspx 
  16. Bjornholt JV, Erikssen G, Aaser E, Sandvik L, Nitter-Hauge S, Jervell J, Erikssen J, Thaulow E. Fasting blood glucose: an underestimated risk factor for cardiovascular death. Diabetes Care. 1999; 22:45–49. Results from a 22-year follow-up of healthy nondiabetic men; see http://care.diabetesjournals.org/content/22/1/45 

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