Functional Health Services for Your Well Being

Diabetes Part II


by Alex Boersma

In part I of this series, I identified Type II diabetes as the most pernicious and calamitous disease of the 21st Century, responsible for destroying the health of millions of Canadians and bankrupting our health care system.  I established that this destructive epidemic is characterized primarily by the inability to regulate blood sugar and is precipitated by a metabolic dysfunction called insulin resistance. 
It is clear that if we expect to mitigate the consequences – both personal and social – of this 21st century epidemic called DIABETES, we must begin with a thorough understanding of all that is known about insulin resistance.  Despite a profusion of misconceptions, the research on insulin resistance is fairly consistent in it’s conclusions.
Sorry, high blood sugar and/or insulin are not up there! 
How can this be?  Didn’t we say that diabetes was characterized by the inability to regulate blood sugar?  Didn’t we say that too much sugar in the blood caused heart disease and blindness and all that other bad stuff?  Didn’t we say that dietary fat was incapable of raising blood sugar levels?
Well, all that stuff is true too!
Confused yet?  Not to worry.  Obviously, the bold statements outlined above are provocative.  I’ve placed them there to emphasize that subtlety and context play significant roles in understanding insulin resistance.  The truth is, disruption of sugar metabolism is a consequence of insulin resistance, not a cause of it.  The truth is, the biochemistry of insulin resistance is incredibly complex.  And since I get the impression that most of my readers are less than fascinated with biochemistry, I shall restrain myself.  Let’s keep this simple:
free fatty acid consequences


The diagram above provides a succinct overview of how fat in your body affects sugar in your body.  The spiky grey blob that looks like it might be exploding is adipose tissue – known to us as muffin-tops, cottage cheese, beer bellies and love rolls.  Adipose tissue is responsible for storing fat when times are good (like – all the time) and releasing fat for energy when times are bad (like – never).  Adipose tissue deals in Free Fatty Acids (FFA).  When times are good it takes FFA out of the blood and stores them for future use.  When times are bad, it releases FFA into the blood to be used for energy.  A whole bunch of hormones, which are mostly associated with stress tell the adipose tissue to release FFA.  One hormone, insulin, tells the adipose tissue to stop releasing FFA.

When FFA concentrations in the blood are chronically high, FFA make their way fairly easily into liver, muscle and pancreatic cells where they interfere with insulin signalling (see here if you are more interested in the biochemical details)    In the liver, insulin is supposed to decrease the rate of glucose production.  When FFA levels in the liver cells build up, the signal to down-regulate glucose production is impaired.  Thus, liver cells continue to dump glucose into the blood even when blood sugar levels are already dangerously high.  In the muscles, high levels of FFA stop muscle cells from absorbing glucose out of the blood.  Thus, blood sugar levels stay high.  In the pancreas, chronically elevated FFA levels can interfere with the secretion of insulin.  Thus, the pancreas fails to react appropriately to high blood sugar levels.
I told you fat was evil!”
Here’s the thing.  FFA have very little, if anything, to do with the amount of fat we eat.  When we eat fat, most of it gets carried through the blood in transport molecules called chylomicrons.  You see, FFA are not water soluble, so they do not travel well through the blood on their own.  They have to be carried in something which is water soluble.  Hence fats you eat are carried primarily by chylomicrons, while fats your liver makes are carried mostly by other transporters called VLDL.
When you eat a mixed meal, most of the fats in it will be carried by the chylomicrons to the adipose tissue, where the FFA will be liberated from the chylomicrons and quickly absorbed into the fat cells.  Most of the carbohydrate in the meal will be burned preferentially for energy or stored in the liver and muscle tissues.  Once your body has safely brought blood sugar levels back to normal and begins to use up some of the stored sugar, it shifts gears.  Now it starts to liberate FFA from the fat cells so that these can be used for energy, sparing the sugar for essential needs.  If everything is working properly, only enough FFA will be released to provide energy…very little will be stored in the liver, muscles and pancreas.
So if eating fat doesn’t cause FFA levels to go up, what does?
Broken fat cells.    Fat cells have a purpose in life.  That purpose, as described above, is to store dietary fat until such time as it is needed and then to release that stored fat in physiologically appropriate doses.  If you suffer from insulin resistance, there is a good chance you have yourself a set of broken fat cells.  They are either not storing FFA appropriately or they are releasing FFA inappropriately (or both).  Either way, you get to take a trip to the pharmacy for a glucose meter and some blood sugar medication!
The $600 billion dollar question, of course, is “How did my fat cells get broken?”  The answer, according to many medical professionals is “It’s in your genes”  But although there is certainly a strong genetic component  describing susceptibility to insulin resistance, I feel that the genetic “answer” is not particularly useful.  Genetics can only tell us about predispositions.  They can tell us very little about what to do concerning those predispositions.  My car, just like about half of North America’s fat cells, is predisposed to break down.  If I treat it properly, it will keep me commuting for many years to come.  If I abuse it, then not so much. 
Fat cells, like cars, can only take so much abuse.  If you are lucky enough to pick the right parents, then you get Toyota fat cells.  You can keep stuffing them with fat forever and they never seem to break down.  Doesn’t do much for the way you look in spandex, but you remain sensitive to insulin even when you weigh 300 pounds.  If, on the other hand, you pick the wrong parents, you get Lada fat cells.  Lada fat cells don’t care that you still look great in a pair of daisy dukes.  Lada fat cells will break down after a couple of servings of Thanksgiving turkey!
When fat cells reach their genetically predisposed limit, they don’t absorb FFA very well, yet they continue to release them into the blood (more excellent biochemistry here).  Insulin resistance is quick to follow.  Depending on what kind of fat cells your parents gave you, this may happen even though you are still relatively thin or not until you are significantly obese. 
Fat cells in the upper body, particularly in the abdominal area, are much more likely to get FUBAR than fat cells in the lower body (more biochemistry anyone?  look here).   Seems like upper body fat cells have either a more limited capacity to absorb fat or a more limited capacity to reproduce themselves than fat cells in the lower body.  Or both!  Either way, carrying fat in your upper body, especially in your abdominal area, is highly associated with diabetes, metabollic syndrome and heart disease.  Fat in your lower body has little effect on health, it just makes wearing short shorts a fashion faux pas.

fat belly  


Adipose tissue acts as a buffer for fluctuation in fat intake.  (you know the drill – click herefor more in-depth info).  Fat cells, as we have discussed, are designed to take fat out of the blood, store it for future use, and release it when necessary.  Without fat cells, FFA concentrations would skyrocket every time you ate a mixed meal.  Without fat cells, your entire body would be resistant to insulin unless you ate a really really really (a-la Dean Ornish really) low fat diet and even then only if you were very careful never to overeat.  Fat cells, then, protect you from insulin resistance.  Unless, of course, you over-stuff them with fat!

cortisol and ffa

If you recall, when we talked about the hormones which affect FFA storage and release, I said that most of the hormones which tell fat cells to release FFA are related to stress.  From an evolutionary perspective, this makes good sense.  If you are being chased by a lion, you want energy available.  Insulin puts energy into storage, making it relatively unavailable.  Cortisol, which is the primary stress hormone, directly opposes the actions of insulin.  (If you still feel you might like to take up a career in biochemistry, find out more here).  Cortisol tells the liver to keep making sugar available, even if blood glucose levels are already high.  Cortisol tells the fat cells to release FFA, even if FFA concentrations in the blood are already high.  Cortisol even opposes the satiating effect of insulin,  telling you to eat more even if you aren’t energy deficient.
This is all well and good if you actually live a lifestyle which includes the occasional chase by a lion.  Cortisol, which doesn’t actually get you away from the lion (adrenalin does that), will help heal your wounds if he gets a piece of you.  It will also help get you ready for the next chase if he decides he wants another piece of you.  An over-abundance of energy is just what the body needs after a near death experience!
Unfortunately, very few people today engage in lion evasion.  For many of us, stress is chronic instead of acute.  For many of us, chronically elevated cortisol levels are a fact of life.  Which means, for many of us, that FFA are constantly being released inappropriately, contributing to a chronic down-regulation of insulin sensitivity.  
inflammation and insulin resistance 3 
 The diagram above depicts how inflammation is implicated in the development of obesity-related insulin resistance.  We see, from the left, that the location and mass of your adipose tissue interacts with other factors to produce macrophage infiltration.  The more fat cells you have and the more they are located in your gut, the more infiltration you get.  Macrophages are immune cells, and when you overload your fat cells, these immune cells weave their way into your adipose tissue and become highly inflammatory.  When this happens, your fat cells start sending out pro-inflammatory hormones called cytokines, which interfere with insulin sensitivity throughout the body.
This review provides an in-depth discussion about the relationship between obesity, inflammation and disease.  Coles Notes version:
  1. Adipose tissue releases hundred of biologically active molecules.
  2. These molecules, called adipokines, work as a network to regulate inflammation, insulin action and glucose metabolism.
  3. Over-stuffed fat cells disrupt this network and create a systemic inflammatory state
  4. This inflammatory state contributes significantly to insulin resistance and disrupted glucose metabolism

But there’s more to inflammation than FUBAR bellies and muffin tops.  The truth is, over-active immune systems are probably the product of multiple factors including infectious diseases, intestinal permeability, glycation end products, auto-immune reactions and oxidative stress.  The complex nature of the relationship between these factors is beyond the scope of this article but the graphic below provides some insight into the labyrinth of complexity involved.


Let’s just say that the absence of obesity is not a sufficient condition for the implication of freedom from inflammation or insulin resistance. This paper ”Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes” is a great reference for those who wish to look further into these relationships.



Amongst a plethora of other vital functions, the liver acts as a fat processing plant.  It recycles fats that are already in the blood.  It manufactures fat out of extra sugar in the blood.  And, when the process of manufacturing and recycling fat gets backed up, it stores the accumulated excess.  In case you were wondering, the part about storing the accumulated excess is not a good thing.
Livers that have stored too much fat become resistant to insulin. Insulin, in case you’ve forgotten, tells your liver to stop exporting glucose and start manufacturing  fat.  If your liver stops listening to your insulin, it adds glucose to the already hyperglycemic blood and fat to the already fattened liver.  The hyperglycemia will enhance production of advanced glycation end products (AGE) which will cause inflammation, which will cause even more hepatic (liver) insulin resistance.  Meanwhile, the liver continues to store more fat, also contributing to hepatic insulin resistance.  Can anyone say “Vicious circle!”?
Once again, the $600 billion dollar question is:  “How did my liver get fat in the first place?”  The obvious answer, “Your liver is fat because you put too much fat in it!”  brings us back to thinking that perhaps Dean Ornish actually knows what he is talking about.  But while putting too much fat in livers does cause livers to get fat, the simplistic corollary “Don’t eat so much fat if you want a skinny liver!”  is, at best, misleading.  Remember, earlier, we said that the fat you eat gets packaged in chylomicrons and travels directly through the circulation to the fat cells where it is stored for future use?  There was no “Stop at the liver for processing”  in that statement.  In reality, most dietary fat should end up either being used for energy or stored in the adipose tissue.  The fatty remnants which do make it to the liver should easily be recycled and sent back into circulation.
Of course, if you have over-stuffed your fat cells, the ensuing high concentrations of plasma FFA will eventually lodge themselves in the liver, causing insulin resistance there.  However, this usually happens only after some level of systemic insulin resistance has already been established.  We are more concerned here with the extent to which fatty liver disease precedes insulin resistance.
Fatty liver, known as Non Alcoholic Fatty Liver Disease (NAFLD) has not been thoroughly researched.  This is probably because it was not even recognized as a disease until about 30 years ago.  Before then, a fatty liver was almost always associated with alcohol abuse.  Since then, most of the research has been conducted on rodents and must, therefore, be interpreted with a grain of salt.  Still, much of the rodent research makes sense when examined in the light of modern dietary trends.
In rodents, consumption of high levels of polyunsaturated fat (most common to us as vegetable oil and fish oil) contribute significantly to NAFLD.  We know that polyunsaturated fats are highly susceptible to oxidation, which also seems to be a significant factor in NAFLD in rodents.  High fructose (think sugar, pop and high fructose corn syrup also induces NAFLD in rodents, especially when combined with trans fats.  Fructose, which is metabolized in the liver using the exact same pathway as alcohol, has been implicated in human NAFLD as well.  It seems that the metabolism of fructose depletes the liver’s stores of anti-oxidants, paving the way for hepatic inflammation.  Finally, it is very clear that a choline deficiency can quickly induce NAFLD.  Choline, found primarily in liver and eggs  is an essential mineral in the transport of fat out of the liver, so without it, the liver stockpiles excessive fat.
Wow!  That was a lot of information jammed into one paragraph!  But here’s the interesting part.  The standard American diet (SAD) is, wait for it:
  1. high in polyunsaturated fat
  2. high in fructose
  3. high in  trans fatty acids
  4. low in anti-oxidants
  5. and, at least if you listen to conventional wisdom, low in choline rich foods like eggs and liver


Hmmm.  What an interesting coincidence!



I know, this was nowhere near as short as I had expected it to be.  Nor was it anywhere near as simple as I claimed it would be.  What can I say?  Things get more complicated when you try to explain them.  If you’re still with me, thank you for your perseverance.  Here’s a quick summary to help you organize your thoughts.

Insulin resistance is not caused directly by high carbohydrate diets or high blood sugar.  Although the quality of carbohydrates in your diet may contribute to inflammation and/or a fatty liver, carbohydrates as a general macro nutrient have not proven to be causative.  As we shall see in part III and IV, the dietary restriction of carbohydrates is probably only necessary after insulin resistance has already been established.  As long as you remain sensitive to insulin, a preventative approach will focus more on minimizing fructose (and possibly grains) rather than simply restricting carbohydrates in general.

Instead, insulin resistance is caused by excessive concentrations of free fatty acids and inflammatory cytokines circulating throughout the body.  Over-stuffing your fat cells beyond their genetic capacity will most-assuredly contribute to both excess FFA and inflammation.  Beyond that, optimizing liver health, avoiding or controlling stress, and preventing low-grade, systemic inflammation are the most important factors to consider in preventing and/or reversing insulin resistance. 

To book an appointment online, please go to or call 519 939 9034
Copyright © 2009 Total Body Health Studio, All rights reserved.