- [Voiceover] Oftentimes we think of diabetes mellitus
as a chronic disease that causes serious complications
over a long period of time if it's not treated properly.
However, the acute complications of diabetes mellitus
are often the most serious,
and can be potentially even life threatening.
Let's discuss one of the acute complications of diabetes,
known as diabetic ketoacidosis, or DKA for short,
which can occur in individuals with type 1 diabetes.
Now recall that type 1 diabetes
is an autoimmune disorder.
And as such, there's an autoimmune destruction
of the beta cells in the pancreas,
which prevents the pancreas from producing
and secreting insulin.
Therefore, there is an absolute insulin deficiency
in type 1 diabetes.
But what exactly does this mean for the body?
To get a better understanding, let's think about
insulin requirements as a balancing act
with energy needs.
Now the goal here is to keep the balance in balance.
As the energy requirements of the body go up,
insulin is needed to take the glucose out of the blood
and store it throughout the body.
Normally in individuals without type 1 diabetes,
the pancreas is able to produce enough insulin
to keep up with any amount of energy requirement.
But how does this change is someone has type 1 diabetes?
Well since their pancreas cannot produces as much insulin,
they have an absolute insulin deficiency.
Now for day-to-day activities,
this may not actually cause any problems,
because the small amount of insulin that is produced
is able to compensate and keep the balance in balance.
However, over time, as type 1 diabetes worsens,
and less insulin is able to be produced,
then the balance becomes slightly unequal.
And this results in the sub-acute or mild symptoms
of type 1 diabetes such as fatigue,
because the body isn't able to match
these energy requirements.
But what happens if the body is placed in a state of stress,
such as with an infection?
Now these stress situations require
a tremendous amount of energy,
and the balance ends up getting tipped to a point
where the body is far from being able to compensate.
And this is the situation in which
diabetic ketoacidosis occurs.
And when this happens, metabolically speaking,
the body goes into a starvation state.
Now this is not necessarily a true state of starvation
because someone with type 1 diabetes
is still able to eat and bring in nutrients.
However, without an adequate amount of insulin,
the body is not able to utilize these nutrients for energy.
And in this sense, type 1 diabetes can be thought of
as a starvation in the face of plenty,
as glucose is present, in fact it's present in excess
in the blood, however the body is not able
to utilize it for energy.
So the body reacts as if it is starving,
which in some senses it is.
So how does this starvation metabolism then
result in diabetic ketoacidosis?
Well, first let's start with the goal
of starvation metabolism, and that is to preserve
energy for crucial, life sustaining organs,
and the most important of which is the brain.
And one thing you need to know about the brain,
is that when it comes to energy, the brain is very picky.
The brain can't utilize many forms of energy.
In fact, there are only two forms of energy
the brain can use, and these are
glucose and ketones.
And if it has to choose between the two,
it prefers glucose.
So the goal of starvation metabolism
is to convert other forms of nutrients
such as fat, protein and glycogen into glucose and ketones.
Now in order to understand the clinical presentation
of diabetic ketoacidosis,
we need to discuss a few metabolic pathways
that occur throughout the body.
So I like to think of metabolism
as being similar to a pawn shop.
At a pawn shop, the goal is to convert
different items of value, such as precious stones or gold
into a usable form of currency in the form of cash.
Now in metabolism, there are many different forms of energy,
such as proteins in muscle,
and the triglycerides, or lipids that are in adipose tissue.
However, as I just mentioned,
they're not usable by the brain.
So they need to be converted into usable forms of energy,
such as glucose and ketones.
And this most commonly occurs within the liver,
which can be thought of as the metabolic pawnshop.
And there are a few important pathways
for the conversion of these energy sources
into glucose and ketones,
and these pathways are driven by the interaction
between many different hormones.
Now, fortunately, the names of all these pathways
will help give us an idea of what they do.
So we'll start with proteolysis,
which occurs within muscle cells.
If we look at the name, lysis stands for the breakdown,
and proteo stands for protein.
So proteolysis is the breakdown of proteins.
And in this process, proteins are broken down
into amino acids, which are then carried
through the bloodstream to the liver,
where they take part in gluconeogenesis,
which we'll discuss in just a minute, here.
And similarly, Lypolysis occurs in adipose, or fat tissue.
Now lipo stands for lipids, which are another term for fats.
And once again, lysis stands for the breakdown of.
And in this process, the triglycerides
that are within lipids are broken down
into their component parts, which are glycerol
and free fatty acids.
And they are then carried through the bloodstream
to the liver to take part in gluconeogenesis.
And it's important to note that this process
also produces some inflammatory cytokines,
which will become important in just a little bit, here.
Now let's move on to gluconeogenesis.
If we look at the name, neogenesis stands for
the creation of, and glucose represents glucose.
So gluconeogenesis is the creation of glucose,
which as you recall, is one of the primary goals
of starvation metabolism.
So how does this work?
Well, the amino acids from proteolysis in the muscle cells
and the glycerol and the free fatty acids from
the lipolysis in the adipose tissue
undergo a series of metabolic reactions within the liver,
that produce glucose.
But this process is not perfect, and in order
to create glucose from free fatty acids and glycerol,
a by-product known as acetyl CoA is produced,
and then utilized later in the ketogenesis pathway.
So we mentioned that the purpose
of starvation metabolism is to produce glucose and ketones.
So the ketogenesis is where ketones come in here.
And it's the metabolic pathway for the creation of,
or the genesis of ketones.
And it utilizes the acetyl CoA from gluconeogenesis,
which then undergoes a series of reactions
to produce ketones.
Then the last pathway to mention is that of glycogenolysis,
which is the lysis, or breakdown of glycogen.
So glycogen is a storage form of glucose.
And essentially all it is, is a polymer
of many different glucose molecules,
or a chain of glucose molecules
that are linked to one another.
And in glycogenolysis, glycogen is broken down into glucose,
which is once again, one of the primary goals
of starvation metabolism.
Now as you can see, there's a lot going on here,
but by understanding these metabolic pathways,
we can gain a clearer understanding
of the clinical presentation of diabetic ketoacidosis.
So what is this clinical presentation?
First off, someone in DKA is very sick,
and likely became sick over a fairly short period of time,
maybe just a few hours to days.
And they most commonly complain of
abdominal pain, nausea, and vomiting.
In addition, they are severely dehydrated,
and therefore their skin may appear cool and clammy.
Then lastly, and most alarming, many individuals
in diabetic ketoacidosis will have an altered mental status,
meaning they may be confused or even unconscious.
So why do all of these symptoms occur?
So nausea, vomiting and abdominal pain
are pretty non-specific symptoms,
but they are very common in diabetic ketoacidosis,
and these symptoms occur because of these
inflammatory cytokines that are released from lipolysis,
and other metabolic processes.
And then these cytokines irritate
the gastrointestinal tract, resulting in these symptoms.
Now, unfortunately, the loss of fluid from vomiting
leads to the next clinical symptom, which is dehydration.
However, the dehydration that occurs
in diabetic ketoacidosis is extremely severe,
and much more severe than what's caused
by the vomiting alone.
But why exactly is this?
Well, we discussed earlier that the goal
of starvation metabolism is to produce glucose.
So what's the problem here?
Well, remember, the patient has diabetes.
And if there's a deficiency of insulin,
then the body is not able to pull all of this glucose
out of the blood to either store it
or utilize it for energy.
So the body is acting like it's starving,
and it continues to produce all this glucose
despite its not being able to use it.
And the glucose then builds up and builds up in the blood,
resulting in hyperglycemia, or high blood sugar levels.
Now when the kidneys are filtering blood,
they are normally able to reabsorb
all of the glucose that's in the blood.
However, at a certain point of hyperglycemia,
the amount of glucose in the blood
exceeds the kidney's ability to reabsorb it,
and glucose begins to spill out into the urine.
And this is a process called glucosuria.
And glucose is an osmotically active solute in the urine.
This means that glucose sucks the water
that's in the bloodstream out into the urine with it,
and this is known as osmotic diuresis,
or the loss of water due to an
osmotically active solute.
And it's this osmotic diuresis that causes the severe
fluid loss and dehydration in diabetic ketoacidosis
that can lead to an altered mental status.
Now once again, it's not just the dehydration
that causes the altered mental status
in diabetic ketoacidosis.
It is made worse because of the consequences
of ketogenesis.
So ketones, or ketone bodies, are an important source
of energy for the brain and heart
during times of starvation.
However, they come at a trade-off,
and that is that ketone bodies are acids,
so they lower the pH of the blood,
a process known as acidosis.
And the body is able to buffer this effect to an extent,
however, in DKA, the ketones are produced
in such large quantities that it overcomes
the buffering ability of the body,
and results in acidosis.
And since it's due to a metabolic process,
it is known as a metabolic acidosis.
And metabolic acidosis worsens altered mental status,
and also if it's severe enough, it may even cause
cardiac arrhythmias, or abnormal heart rhythms,
that can be fatal.
So you can see here that the clinical presentation
of diabetic ketoacidosis is directly tied
to the underlying metabolism that's caused
by the starvation state,
or perhaps, as we said earlier, better put,
the starvation in the face of plenty
that occurs in type 1 diabetes.
And anytime someone with type 1 diabetes
presents with abdominal pain, altered mental status,
and signs of dehydration,
DKA, or diabetic ketoacidosis, should be very high
in the differential for the cause of their illness.
And they will need to be treated quickly and aggressively
with intravenous fluids and insulin,
because if it's left untreated,
diabetic ketoacidosis can be fatal.