Insulin Resistance is Good? – T2D 7
says that insulin resistance is bad. Very bad. It’s
the root cause of type 2 diabetes (T2D), and metabolic syndrome, isn’t it? So,
if it is so bad, why do we all develop it in the first place? What’s the root
cause? My friend Dr. Gary Fettke from Tasmania wrote an illuminating book
called ‘Inversion’ where
he describes how you can learn a lot from
looking at things from another perspective. Invert (turn upside down) your
perspective, and see how your horizons are immensely broadened. So let’s look
at why we develop insulin resistance. Why is it good?
Root Cause Analysis
is the root cause of insulin resistance? Some people say inflammation or oxidative
or free radicals causes insulin resistance [jk says fatty liver]. Those are
total cop-out answers. Inflammation is the body’s non-specific response to
injury. But what causes the injury in the first place? That’s
the real problem. The inflammation is only the body’s response to whatever is
causing the injury.
about it this way. Suppose we are battlefield surgeons.
After decades on the job, we decide that blood is bad. After all, every time we
see blood, bad things are happening. When we don’t see blood, bad things are
not happening. It must be the blood that is dangerous. So, deciding that blood
is what is killing people, we invent a machine to suction all the blood of
people. Genius! The problem, of course, is what’s causing the bleeding,
rather than the blood itself. Look for the root cause. Bleeding’s
only the response, not the cause. Bleeding is a marker for disease. So is
causes bleeding, the body’s non-specific response.
Something causes inflammation, the body’s non-specific response. Gunshots cause
bleeding, knife wounds cause bleeding, and shrapnel causes bleeding. Those are
root causes. You got shot. You bleed. But the problem is the gunshot, not the
bleeding. The same applies to inflammation [same for hypertension, its
is causing the injury (the root cause) is also
stimulating inflammation (the nonspecific response to injury). Inflammation
is simply the marker for disease. So people say that cardiovascular
disease, diabetes, neurodegenerative disorders, obesity and cancers all
involve chronic inflammation. But the inflammation is not causing the disease,
it is only a marker of it.
inflammation was actually a root cause of heart disease, for
example, then anti-inflammatory medications (prednisone, ibuprofen, NSAIDs)
would be effective in reducing heart disease, or obesity, or cancer. But they
are not. Whenever people talk about inflammation being the cause of disease,
they just bandying around the latest buzzword [put out by pharma’s KOLs].
is not to say that inflammation (or bleeding) is not useful
as a marker of disease. If the bleeding stops, then the treatment (tourniquet)
is highly likely to be effective. But it’s not effective because bleeding
stopped. It was effective and bleeding stopped (it’s a marker for
effectiveness). Similarly in inflammation and T2D, as I previously wrote, insulin therapy does not decrease
inflammation, which marks this likely an in-effective treatment overall.
same goes for oxidative stress (or free radicals). Tell me
what is causing the oxidative stress. That’s why antioxidant
therapy is so startlingly ineffective. So Vitamin C, or E or N-acetylcysteine
or other antioxidant
therapies never work whenever they are tested rigorously. Because the oxidative
stress is only the response (like inflammation) to whatever the underlying
disease process actually is. If somebody goes on and on about oxidative stress
(or free radicals or inflammation, or bad gut microbiomes) as the cause of XXX
disease, run, don’t walk the other way. “Insulin resistance is caused
by inflammation” is like “gunshot wounds are caused by bleeding”.
back to insulin resistance. Why does the body develop it so
frequently (up to 50% of the American population)? This simply cannot be
mal-adaptive. Our bodies are not designed to fail, since we lasted for several
millennia before the modern diabesity epidemic. Insulin resistance must serve a protective
function, being so common.
Maybe this IR is actually protective. Regulation of insulin sensitivity
is part of the normal physiologic response – it can go up or down depending on
lots of things, including other hormones (eg. pregnancy) or availability of
nutrients. So how can IR be protective?
this. Excessive glucose in the blood is bad for us (high
blood sugars). If this high glucose level is toxic in the blood, why wouldn’t
it also be toxic in the body, too? Shouldn’t
we get rid of the toxic levels of glucose instead of merely shoving it from the
blood into the tissues of the body? After all, insulin doesn’t actually get rid
of the glucose. It shoves the excess glucose out of the blood and forces it
into the body. Somewhere. Anywhere. Eyes. Kidneys. Nerves. Heart [that’s bad
for those tissues].
you have too much garbage in your house. But you like to
keep your chair nice and neat by moving everything elsewhere. Instead of
actually throwing the garbage out of the house, you merely shift it around in
the same house. Not a great idea. For glucose, instead of reducing the total
amount of whole-body glucose, we merely shove it from the blood into the body.
if this high glucose is toxic, then the natural response of
the tissue (body) is to protect itself against this excessive glucose load.
Suppose you live on a street of houses in Diabetes Ville (each house is a cell
of the body). Everybody is friendly and normally leaves their door open (just
as a cell is open to glucose in the insulin sensitive state). A truck full of
toxic waste (glucose) comes down the street. And the garbage-man (Insulin)
really wants to get rid of this slime. So, every time he sees a door open, he
shovels in some toxic waste (glucose).
a few days of this, what would you do? You’d bar your
f***ing door, is what you’d do! You’d say,”I don’t want this toxic slime!”
That’s insulin resistance, baby! You make it really difficult to shove that
toxic stuff into your house. It’s not a bad thing, it’s a good thing. The
insulin resistance is trying to protect the cell from the toxic levels of
glucose that the insulin is trying to shove in the door.
is Insulin Resistance protecting us from?
It’s very name gives the answer away, Insulin
Resistance. It’s a reaction against excessive insulin. It’s
protecting us from the excessive insulin. In other words, as we’ve written
before, Insulin causes Insulin Resistance. But the root
cause here is the Insulin, not the Insulin Resistance. The tissues
(heart, nerves, kidney, eyes) are all busy increasing their resistance to
protect themselves from Insulin which is trying to shove some toxic glucose
into their house.
we call the specialist Dr. Endocrine. Dr. Endo decides that the
slime is indeed toxic, and we must get it off the streets immediately. There
are some options – like reducing the production of toxic glucose (Low Carb
diets) or burning off the toxic glucose (Fasting). But instead, he decides that
he will hire more garbage men (insulin) to shove this toxic glucose into the
houses. At least then, Dr. Endo won’t be able to see it anymore. Now Dr. Endo
can pretend he is doing a great job. Look! The streets are nice and clean. But
all the toxic glucose goes into the houses (tissues).
what happens over time? Well, all the tissues of the body just
start to rot. We are inadvertently ‘overcoming’ the tissue-protective insulin
resistance developing. Instead of targeting the insulin, and reducing the total
amount of glucose that we have to deal with, we are increasing how to get rid
of it. So, by prescribing lots of insulin for patients, we are not making
things better, we are making them worse.
– Technical talk ahead – feel free to skip ahead.
Normally, there is an inverse relationship between blood glucose and free fatty
acid (FFA). In the fasted state, glucose is low and FFA is high. The body is
burning fat for energy. As you eat, insulin goes up, glucose goes up and
lipolysis is inhibited and FFA levels fall.
in T2D, insulin levels are high. Glucose is high. But because
of excessive IR, FFA is also high. So, the tissues of the body are now at risk
of receiving both excessive glucose and fat, which is now causes the oxidative
stress and the inflammatory response. But the inciting factor here, is the
excessive glucose and insulin. (See pretty picture above for graphical
explanation). Excess glucose to the mitochondrion overloads the electron
transport chain and results in excessive ATP production as well as Reactive
Oxygen Species – all causing oxidative stress.
metabolized through the anaplerosis pathways that produce
AcCoA and MalCoA which becomes substrate for cholesterol and fatty acid
synthesis. MalCoA inhibits FACoA resulting in steatosis, or the production and
abnormal deposition of this fat.
technical speak over. Welcome back. So, in the liver,
excessive insulin produces fatty liver. We can easily demonstrate this in
humans. In this study, 16 test subjects were overfed an extra 1000 calories of
sugary snacks per day. This consisted of 1 can of Pepsi, 30 ml of fruit juice
and a bag of candy. Over 3 weeks, there was only a 2% increase in total body
weight. However, there was a disproportionate
27% increase in liver fat due to DeNovo Lipogenesis. [At http://ajcn.nutrition.org/content/96/4/727.short
and http://ajcn.nutrition.org/content/96/4/727.full. It took them a subsequent 6
months of energy restricted diet
to lose the excess liver fat and another 10%.]
other words, insulin is driving much of this excess glucose
into the liver and it’s being turned into fat. Some of this fat can be exported
out of the liver to other tissues such as muscle and pancreas giving you ‘fatty pancreas’.
the muscle cells, we get fat deposits between the strands of
muscle. You could call this ‘fatty muscle’. Technically, this is called intramyocyte
lipid accumulation. Many think this causes insulin resistance,
but it is more likely the result of excessive glucose and insulin.
The accumulation of fat between muscle fibres (where there should not be any),
in cattle, is called delicious.
of course, know exactly how
to develop marbling in cows. The most important determinant is
the type of feed. Cows are ruminants, which means that they normally eat grass.
However, by feeding a high energy, grain
heavy diet, ranchers can increase the growth rate of cows as well as
if you can spot the difference between well marbled beef and
lean beef. The
grass fed beef develops no marbling,
which gives steak much of its flavour. For this reason, many grass fed cows are
‘finished’ with feeding corn in order to develop the fat marbling. Insulin and
glucose. No secret. It works in humans as well.
can see the same sort of fat deposits in the muscle cells of
the heart and this may contribute to congestive heart failure. ‘Fatty Heart’.
A New Paradigm
inversion forces us to see T2D from a new perspective. The
toxic agent here is the excessive glucose, and its co-conspirator, insulin.
Moving the toxic glucose out of the blood and forcing it into the body has no
net benefit, as has been amply demonstrated by multiple long term randomized
studies – ACCORD, ADVANCE, VADT, and ORIGIN.
insulin resistance develops precisely because
it is a protecting the tissues against the blood trying to shove all its toxic
load into the cells. This is why the development of the insulin resistance is
universal. It’s a good thing, not a bad one. Giving
exogenous insulin to overcome this IR is actually detrimental. So the problem
is not the IR at all. Instead, look for the root cause – the excess
glucose and excess insulin. Take that away, and the T2D goes away.
there are good treatments for T2D, and there are bad ones. The bad ones overcome
the tissue insulin
resistance which is there precisely to
protect the tissues. These are insulin and sulfonylureas. The good treatments get rid of the glucose out of
the body. You can do this by preventing it from coming into the body
in the first place (LCHF diets, Acarbose),
burning it off (Fasting) or urinating it out (SGLT-2 Inhibitors). This
explains the power of this new class of medication in terms
of cardiac protection.
Insulin resistance is bad? No,
not at all. It is good. Insulin resistance is not the root cause. It’s the
natural, protective reaction to the root cause – high insulin levels. It’s
the insulin, stupid!