16-year-old (male) with type 1 diabetes

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.