00:01
The parents of a 16 year old boy with type 1
diabetes visit the clinic for information
regarding a new injectable drug, exenatide that
only needs to be administered once a week.
00:14
They are quite excited about the prospect
of switching their son's medication
as he currently requires several
shots of insulin each day.
00:23
The boy's blood glucose levels are quite difficult to
control on his current regimen due to poor adherence.
00:29
His BMI is 19 (kg/m2)
He has had difficulty putting on
weight despite eating quite a bit.
00:35
Which of the following best describes
why it is not possible to start
the boy on a weekly dose of
exenatide instead of daily insulin?
Answer choice (A) - insulin production by the
pancreas is insufficient for exenatide to function.
00:51
Answer choice (B) - exenatide suppresses glucagon
secretion which increases the risk of hypoglycemia.
00:59
Answer choice (C) - suppression of appetite
makes it even harder for him to gain weight.
01:04
Answer choice (D) - exenatide is
contraindicated in children below 18 years
And answer choice (E) - gastric
emptying is inhibited by exenatide.
01:15
Now take a moment to come to the answer by
yourself before we go through it together.
01:22
Okay let's jump right in.
01:23
Let's review the question characteristics.
01:25
Now this is a pharmacology question.
01:27
We're reviewing a medication for diabetes and
seeing if it's applicable to the patient.
01:32
Now this is a 2-step question.
01:35
We first have to determine what type 1 diabetes
is with respect to the pathophysiology
and then determine if the drug in question
her is applicable for this disease.
01:46
And the stem is absolutely required to determine the patient's
clinical history to see if it's applicable to give him this drug.
01:53
Now let's walk through this question together.
01:55
Step 1 - we need to determine the reason
for hyperglycemia in type 1 diabetes.
02:01
And in type 1 diabetes, the pancreas produces little or no insulin
due to destruction of beta cells in the islets of Langerhans.
02:10
Now that's how type 1 diabetes works.
02:13
Now for step 2, we need to determine the mechanism of action
of exenatide and its suitability for type 1 diabetes.
02:21
Now, exenatide is a glucagon-like peptide-1 receptor
agonist or what's also called a GLP-1 receptor agonist.
02:31
Now let's review how this works by looking at our image,
where GLP-1 therapeitic mechanism of action is reviewed.
02:39
Now looking at our image, we see that food is
consumed and goes through the small intestine.
02:43
And in the small intestine, food stimulate
the small intestine to secrete GLP-1,
and then GLP-1 actually
stimulates the pancreas.
02:54
And doing so, GLP-1 stimulates
the pancreas to release insulin,
it also suppresses glucagon secretion
and gastric emptying is slowed.
03:05
Now, if we have a GLP-1 analog such as
exanetide, it mimics the action of GLP-1
and then whenever food is consumed, it will cause
the stimulation of the pancreas to release insulin.
03:19
And that's how these GLP-1
analogs work such as exanetide.
03:24
Now let's go back to our question to see if
this information helps us determine the answer.
03:29
Now, exanetide increases insulin secretion
from the pancreas in response to meals,
and thus exanetide actually is indicated
in type 2 diabetics but not type 1.
03:41
And thus exanetide is not suitable for type
1 diabetics as the few remaining beta cells
in type 1 diabetes are
already maximally stimulated
and providing such medication as the GLP-1
analog will provide no further benefit.
03:55
And also, exanetide generally suppresses
appetite leading to weight loss
with which further would not be in
the best interest of this patient.
04:04
Thus the correct answer is answer choice (A) -
insulin production by the pancreas is insufficient
for the exanetide to function and thus
is not appropriate for this patient.
04:15
Now let's discuss some high-yield facts regarding
type 1 diabetes and GLP-1 receptor agonists.
04:20
Now type 1 diabetes occurs when the
pancreas produces little or no insulin
due to the destruction of beta
cells in the islets of Langerhans.
04:29
The destruction of beta cells is thought
to be due to an autoimmune mechanism
with some type of genetic predisposition.
04:36
The treatment of choice in type 1 diabetics
is insulin as few remaining beta cells
are already functioning at maximal
capacity and cannot be further stimulated.
04:44
So type 1 diabetics lack it
and so we give them insulin.
04:49
Now GLP-1 receptor agonist, that's glucagon-like peptide 1
receptor agonist to a group of what's called incretin mimetics.
04:58
Now GLP-1 receptor agonist increase
insulin secretion from the pancreas
and decrease glucagon secretion by
the liver in response to meals.
05:07
Now GLP-1 receptor agonist are indicated for type 2
diabetes but are not suitable for type 1 diabetes
as the remaining islets are
already maximally stimulated.
05:17
Exanetide is a GLP-1 agonist which also slows gastric
emptying and suppresses appetite leading to weight loss.