Insulin Resistance – Hormonal Obesity VIII

By Jason Fung, MD

Insulin is a major driver of obesity.  But what drives insulin?  In some cases, certain foods drive the increase in insulin.  But there are clearly some time dependent factors about obesity that are unaccounted for.  What am I talking about?

Consider this.  There are people who have been overweight or obese for their entire lives.  For them, it is extremely difficult to lose weight on a permanent basis.  On the other hand, there are people who have only recently gained weight.  For them, it seems that it is much, much easier to lose the weight.  Why is that?

Most conventional theories of obesity do not allow for these effects.  Consider the Caloric Reduction as Primary (CRaP) theory, also known as calories in calories out.  According to this flawed theory, there should be no difference between those who have had obesity for 1 month versus those who have had it for 1 decade.  Having obesity for a long time should make no difference.  But anybody who has tried to lose weight or has known somebody trying to lose weight knows that duration of obesity plays a very large role.

Consider also the carbohydrate-insulin hypothesis.  According to this theory, there is also no allowance for duration of obesity.  It should make no difference.  As long as you reduce carbohydrates, you should lose weight.  But everybody who has struggled with their weight knows that it matters a lot whether you have been obese for months or for years.

Childhood obesity shows the same problem.  Those obese as children tend to be obese as adults.  Why?  Why is it so much harder for them to lose weight.  Children of obese adults tend to be obese.  Why?  Even as 6 month-olds (breast fed so no junk food, don’t walk) there is an epidemic of obesity.  Why?

These are the time dependent effects of obesity.  If we can accept that insulin causes weight gain, then why do high insulin levels over long periods of time tend to make it difficult to lower the insulin levels so that we can lose weight.  Something is clearly missing here.  That missing something is insulin resistance.

What is insulin resistance?  Insulin is a hormone that is produced by the body.  In order for it to have its desired effect, it must bind to receptors in the body that signal what the next step is.

In this example, insulin is acting on the insulin receptor to bring glucose into the cell.  It acts very much like a lock and key. Insulin is the key.  It fits snugly into the lock (the receptor).  Once the key and lock are together, the door opens and glucose is brought into the cell. All hormones work in roughly the same fashion.  In this regard, there is nothing really special about the insulin and insulin receptor. In the case of insulin resistance, the key (insulin) no longer fits very well into the door (insulin receptor).  Because there fit is poor, the door does not open fully and therefore less glucose comes in than normal.

What happens is that the cell now senses that there is too little glucose in the cell.  It is starved for glucose.  The cell needs more glucose.  In order to get more glucose the body produces extra keys (insulin).  The key and lock still do not fit very well, but because there are many more keys, the cell is able to get enough glucose.

This is the situation called insulin resistance.  Why do we care?  Because insulin resistance leads to very high insulin levels.  We care about the high insulin levels because insulin is a major driver of obesity.  As we become obese, we are driven by hormonal factors to eat more to get to our target weight. Not only do high carbohydrate intake lead to high insulin levels, high insulin resistance also leads to high insulin levels.  As we shall soon see, it is this insulin resistance that leads to the time-dependent effects of obesity.

However, there is one important question unanswered.  What causes the insulin resistance in the first place?  Is the problem with the key (insulin) or the lock (insulin receptor).  It is quite easy to measure the insulin and it become clear very quickly that insulin is the same hormone whether it is from a non obese or an obese person.  There is no difference in amino acid sequence or any other measurable quality.

Therefore, we would have to conclude that the problem is not with the key (insulin).  The problem lies in the lock (receptor).  The insulin receptor does not respond quite the same way that it used to.  This is insulin resistance.  What causes insulin resistance?

To begin working it out, we can look at other biological systems.  We can find examples of biological resistance in many places and this may provide us a clue as to what causes insulin resistance.  While not all examples may apply specifically to the insulin/ insulin receptor problem, it may shed some insight into the problem and show us where to begin.

For instance, there is a major problem in many parts of the world with antibiotic resistance. As you use more and more antibiotics, there tends to be a natural selection for antibiotic resistance organisms to survive and reproduce. Therefore, with the continued use of antibiotics, there tends to develop antibiotic resistance.  By understanding this concept, we can see that the key weapon to prevent the development of antibiotic resistance is to reduce the use of antibiotics.  That is, antibiotics cause antibiotic resistance. In parts of the world where there is limited antibiotic use, there is very little antibiotic resistance.  In parts of the world where antibiotics are used liberally, there is much antibiotic resistance.

What about viruses?  What causes us to be resistant to viruses like diphtheria and polio for instance?  Before vaccines were widely available, it was well known to getting a virus causes you to become resistant to further infection by the virus. In fact, vaccines are based entirely on this premise.  By giving dead or weakened virus, we could build up a persons immunity without actually causing the full disease.  That is, viruses cause viral resistance.  And antibiotics cause antibiotic resistance.

These examples, of course, do not apply directly to insulin resistance.  However, it starts to give us a clue that resistance can actually be brought on by the very agent itself.  Could insulin cause insulin resistance?

Continue to Hormonal Obesity IX here
Begin here with Calories I
To see the entire lecture – the Aetiology of Obesity 2/6 – The New Science of Diabesity click here.

By The Fasting Method

For many health reasons, losing weight is important. It can improve your blood sugars, blood pressure and metabolic health, lowering your risk of heart disease, stroke and cancer. But it’s not easy. That’s where we can help.

Jason Fung, MD

By Jason Fung, MD

Jason Fung, M.D., is a Toronto-based nephrologist (kidney specialist) and a world leading expert in intermittent fasting and low-carb diets.

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