Treating type II diabetes – Pharmacology | Endocrine system diseases | NCLEX-RN | Khan Academy

– [Voiceover] Type II diabetes
receives a lot of attention in the laypress as a public health threat, as it affects about 10%
of the global population, and is currently the eighth most common cause of death worldwide. As such, understanding how
to treat type II diabetes is very important because
if it’s treated properly, one can avoid nearly
all of the complications of type II diabetes and live
a happy and healthy life. Now before we dive into
the specific treatments, let’s first discuss the
glucose regulation pathway as it will help us to better understand the pharmacokinetics or
the mechanisms of action for the different treatments
of type II diabetes. Now in the center here is
the blood glucose level, and as blood glucose levels increase, say after eating a meal, this
is sensed by the pancreas, and the beta cells within
the pancreas secrete insulin which acts on cells throughout the body to lower the blood glucose level. Then as blood glucose levels decrease, this is also sensed by the pancreas, and then the alpha cells secrete glucagon which acts to raise the
blood glucose levels. And one of the mechanisms
by which it does so is by promoting the conversion of glycogen to glucose in the liver which is then released
into the blood stream. Now diabetes mellitus
is a group of disorders that’s caused by dysfunction
of the insulin pathway resulting in an inability to
lower blood glucose levels. And as you can see by this diagram, there are two main steps that must occur for this pathway to work properly. First, insulin must be secreted by the beta cells of the pancreas. Then second, the cells throughout the body must respond to insulin
for it to have an effect. And this glucose regulation pathway can be thought of as similar to that of the temperature regulation in a building. The thermostat is
analogous to the pancreas in that it senses the
changes in temperature and sends different signals accordingly. If the temperature
increases, then it sends a signal to the air
conditioner to turn on, which then lowers the temperature. Conversely, if the temperature decreases, this is also sensed by the thermostat and it sends a signal to
the boiler and radiator to turn on, which then
raises the temperature. Now once again, there
are two important steps. The thermostat must sense
the change in temperature and send a signal, which is
similar to the first step in the insulin pathway, and
second, the air conditioner must be able to act upon this signal in order to have an effect. So let’s go back to our insulin pathway. When we think of the types of diabetes, in general we think of type I diabetes as dysfunction of the first step, and type II diabetes as occurring due to dysfunction of the second step. So it would make sense that the treatment of the different types of
diabetes will be different as their underlying
mechanisms are different. In the treatment of type II diabetes, some medications are given to
increase insulin secretion, to help overcome the resistance, and others are given to directly decrease the insulin resistance in the second step. So let’s now discuss
the specific treatments for type II diabetes and the
mechanisms by which they work. And we’ll begin with
lifestyle modifications. The first lifestyle
intervention is that of proper nutrition and weight loss. Regardless of one’s initial weight, proper nutrition and
associated weight loss improves the body’s ability to regulate blood glucose levels. And proper nutrition for type II diabetes includes a well-balanced low-calorie and low-carbohydrate diet. Admittedly, this can be
a very difficult change for many people with type II diabetes. As it takes a great deal of
dedication and self-control. However, it is extremely important because a proper diet and
weight loss have been shown to both increase insulin secretion and decrease insulin resistance. The other lifestyle modification
is physical activity. Independent of weight loss,
increased physical activity has been shown to improve glycemic control through reducing insulin resistance. And the benefits of exercise
begin almost immediately, however they can be short lived if physical activity is not maintained. Persisting only about
three to six days after the cessation of routine exercise. So the recommendations
for routine exercise include 30 minutes a
day, five days a week, of moderate intensity aerobic activity such as walking, jogging, or biking. And the great thing about
these lifestyle modifications is they don’t just treat type II diabetes. A proper diet and
routine physical activity will also improve one’s
cardiovascular function, lipid profile, as well as
their general mental wellbeing. In addition to lifestyle modifications, there are many different medications available to treat type II diabetes, however it can be confusing
to keep them all straight. Instead of discussing
each of the medications individually, let’s classify
the different medications into groups based on
their mechanism of action and how it relates to our
diagram of glucose regulation. And we’ll start with
a group of medications known as the biguanides, and I know I just said
we won’t be discussing the individual medications,
however there is one exception, and that is with metformin. And this is because metformin is by far the most common biguanide
prescribed for type II diabetes. And it’s also the first line
medication for the disease. Now, metformin has three
mechanisms of action that improve glucose regulation. Most importantly, metformin
directly increases the peripheral insulin sensitivity. It also acts by decreasing the action of glucagon in the liver. So instead of just augmenting
the insulin pathway, metformin also inhibits the
opposing glucagon pathway. Then lastly, although not
shown in this diagram, metformin reduces intestinal
absorption of glucose which then decreases the amount of glucose available to enter the blood stream. And fortunately, metformin
is also very effective. On average, metformin can reduce someone’s hemoglobin A1c by about
1%, however it is important to note that individuals
with liver failure can not take metformin
and a small percentage of individuals who take the medication will need to stop taking it due to an adverse side effect
known as lactic acidosis. The next group of medications have a somewhat difficult name. They are the thiazolididiones
or TZDs for short. Similar to metformin,
TZDs also work to increase type II diabetes by
acting on the second step to increase insulin sensitivity, however the means by which
they do so is different. TZDs activate a receptor known as the peroxisome proliferator-activated
receptor gamma or PPAR gamma for short. And PPAR gamma is a transcription factor for multiple genes that
increase insulin sensitivity in adipose, muscle, and liver cells. As such, by activating PPAR gamma, TZDs indirectly increase
insulin sensitivity. Now the next group of
medication is the sulfonylureas which are another common group
of anti-diabetic medication. Sulfonylureas inhibit
the potassium channels on the beta cells within the pancreas and by inhibiting these channels, potassium builds up within the cell and this depolarizes the cell membrane which opens voltage
gated calcium channels. This causes an influx of
calcium into the beta cells which triggers the release of
insulin into the blood stream. So instead of decreasing
insulin resistance, sulfonylureas treat type II diabetes by overcoming the insulin resistance through increased insulin secretion. The last two groups of type
II diabetes medications act upon the incretin pathway, and are therefore known as incretins. And they are the glucagon-like peptide one or GLP-1 agonists and the
dipeptidyl peptidase four or DPP-4 antagonists. Incretins such as GLP-1
are hormones that have two synergistic effects that result in the lowering of blood glucose levels. First, they directly stimulate
the release of insulin from the beta cells in the pancreas. And second, they inhibit
the release of glucagon. DPP-4, on the other hand, is an enzyme that inhibits the action of GLP-1. Therefore GLP-1 agonists can be given to directly stimulate
this incretin pathway to augment the insulin pathway and treat type II diabetes. Similarly, DPP-4 inhibitors can be given to indirectly augment the insulin pathway by inhibiting the inhibition
of the incretin pathway. So it’s important to know
that any of the treatments for type II diabetes that
act upon this first step in the insulin pathway, and therefore increase insulin secretion, will therefore also carry a risk of inducing hypoglycemia or low blood sugar levels. And the treatments that act upon this step and carry this risk include
lifestyle modifications, sulfonylureas, and the incretins. And one way to decrease this risk is to take the medications with a meal. Now this is just an overview of the pharmacokinetics of
the different interventions used to treat type II diabetes and this is helpful for understanding how we can use medications to reverse and treat the underlying
mechanisms that cause the disease, however just understanding the mechanisms does not convey a very practical approach to treating this disease. For most individuals,
treating type II diabetes requires a combination of
lifestyle modifications, potentially multiple medications, and routine care by a
primary care provider to achieve a happy and healthy life free of the complications
of type II diabetes.


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