Okay, let's summarize our drugs in diabetes.
First line agent, metformin.
It increases insulin sensitivity, low risk of hypoglycemia.
TZDs and secretagogues are falling out of favor. The other
drugs have essentially disppeared from therapeutic landscape,
like the alpha glucosidase inhibitors
because of severe side effects.
DPP4's are safe and are often combined with metformin.
Very very commonly used.
SGLT2's are exciting new drugs that
may have evidence of heart failure reduction.
They should not be used in patients who are volume depleted.
There is a study that will be coming out soon talking about
the beneficial effects of SGLT2 in heart failure patients.
And I'm expecting that it's going to be positive meaning that
we may actually see a reduction in mortality morbidity
in the future with SGLT2's.
So keep your eye on this class very closely
because I think they are going to be a blockbuster set of
drugs, and I think that they are going to save lives as well.
Finally, insulin is the mainstay of
type I diabetes, diabetic ketoacidosis,
and that acute patient who is coming into the ER with
high sugar levels and may not have been diagnosed before.
Let's move on to some questions. Insulin inquiry.
The effects of insulin include the following.
It increases membrane transport of glucose
into the hepatocyte using GLUT 2.
B, it increases membrane transport of glucose
into the myocyte using GLUT 2.
It increases membrane transport of glucose
into the adipocyte using GLUT 2.
And finally D, it decreases membrane transport of glucose
into the adipocyte using GLUT 4.
What's the correct answer?
Good, it increases membrane transport of glucose
into the hepatocyte using GLUT 2.
Remember that GLUT 2 is in the liver,
GLUT 4 is everywhere else.
I put this there because believe it or not,
this was on the exam when I was writing the exam,
and I actually got this question wrong.
So I just seem to remember it.
I don't know why they put this on the exams,
but from a pharmacology point of view, it's important,
from a clinical point of view, not so much.
Let's go on to insulin exceptions.
The actions of insulin include the following except.
Increased hepatic synthesis of sucrokinase.
Increased hepatic synthesis of phosphofructokinase.
Increased hepatic synthesis of glucokinase.
Increased hepatic synthesis of pyruvate kinase.
The answer is A, increased hepatic synthesis of sucrokinase.
Insulin does not affect sucrokinase,
in fact, sucrokinase doesn't exist.
Now, what's interesting about this kind of question is that
75 % of medical students got this question wrong.
So, don't be fooled into thinking that pyruvate kinase does not
belong just because pyruvate kinase doesn't sound like a sugar.
Sucrokinase doesn't exist.
Remember pyruvate kinase does exist,
and it is going to be an important enzyme
that is affected by insulin.
Let's do a case in diabetes. This 38 year old woman
wishes to have better control of her type I diabetes.
Her hemoglobin A1c is 11.2 %
with a fasting sugar of 216 or 12.2 millimoles.
Urine is 1+ glucose and positive ketones as well.
She is currently on NPH insulin.
And she takes that NPH insulin at night,
and she takes regular insulin at mealtimes.
What do you think is
the most appropriate therapy for this woman?
A, regular insulin twice daily with NPH at night.
B, glargine insuline in the evening with lispro before meals.
C, insulin NPH twice a day with regular insulin
for breakthrough high sugar values.
And D, insulin detemir before each meal with lispro at night.
Right, insulin glargine in the evening
with lispro before meals.
So, let's take a look at this case. This woman was on
an older regimen of regular insulin before each meal.
And you see this all the time, the old regular insulin
is slowly being replaced with newer stuff.
NPH is taken at night or it used to be.
NPH lasts about 8 hours, it often was used at night,
and regular insulin was often used before meals
to be the mainstay of therapy perhaps 10 years ago.
The regimen is simply outdated
and wasn't achieving the goals.
Regular insulin has been replaced with the new short acting
agents such as lispro and other agents that are very short acting.
Glargine is appropriate at night or in the morning.
Detemir is a long acting agent and
is almost never used twice daily.
Lispro should not be used at night.
Lispro is a short acting drug.
If you have really high levels of insulin therapy,
let's say person is on 100 units,
sometimes we split the long acting doses into two
and that's actually quite reasonable.
But for the most part, if you see detemir or glargine
being split up and they are on low doses,
that's usually not appropriate.
The following is true. A, TZDs act through PPAR
to achieve glucose uptake in muscle and fat.
B, the secretagogues, or sulfonylureas,
inhibit the ATP sodium channel.
C, heart failure incidence is increased with
SGLT2 inhibitors and decreased with TZDs.
And D, DPP4 inhibitors increase glucagon activity
by stimulating the alpha cells.
Okay, A is correct. TZDs act through PPAR
to activate glucose uptake in the muscle and fat.
Now, remember that secretagogues inhibit
the ATP dependant potassium channel.
They don't act on the sodium channel.
Heart failure may be increased by the TZDs, not decreased.
Heart failure may be or has been shown
to be reduced by SGLT2 inhibitors.
DPP4 inhibitors decrease glucagon activity.
Let's do a case. A thin 28 year old male was seen for the
first time with a serum glucose of 250, which is 13.9 mmol/l,
and has 2+ glucosuria. He has been started on metformin 500 mg
bid and canagliflozin 300 mg/day by his nurse practitioner.
3 days later, his serum sugarsare 6.7 mmol/l or 120.
He has 4+ glucosuria and has 4+ ketones in the urine.
He feels nauseated and fatigued. The nurse practitioner is
worried about the glucosuria and asked you to see him.
Pick the true statement. Number 1, or number A,
the worsening of glucosuria is expected and is not a concern.
B, the correction of blood glucose is not a sign
of clinical improvement.
C, the ketonuria is a worrisome sign.
He should be assessed at a hospital and started on insulin.
And D, all of the other choices are correct.
D, all of the other choices are correct.
Now, I want to talk to you about this particular case
because this is the kind of case that gives us headaches
as specialists. We see this actually more and more.
Ketoacidosis needs to be stopped with insulin. And too often,
we think that diabetes is just a disease of sugar.
It's not. It's an entire metabolic process.
Ketoacidosis releases toxins into the body. And the only
thing that will stop the production of ketoacidosis is insulin.
So, we have to put these people on insulin.
We cannot just control the blood sugar.
This person could have died. It's an important thing
to remember that patients who come in with high sugars
for the first time really need insulin therapy.
And correction of the blood sugar is not good enough.
You have to look at the whole patient.
And if these patients have lots of ketonuria,
you have to be very concerned about other problems going on.
There is actually been a few hundred reported cases
of diabetic ketoacidosis exacerbations
because of the initiation of an SGLT2 inhibitor. Now look,
the SGLT2 inhibitor did not cause the diabetic ketoacidosis.
The failure to start insulin allowed it to develop
to the point where a person was getting much sicker.
The normalization of glucose gave false security
and masked a dangerous situation.
Diabetic ketoacidosis requires urgent treatment with insulin,
usually intravenous, with a large fluid bolus,
and possibly intravenous potassium supplementation as well
because remember insulin will make your potassium drop
as you give it to the patient.
So, it's really important that you treat
these patients properly and it will be a case
and in fact that images from
the USMLE exam question very similar.
Well, that's it for diabetes. I hope you do well on your
exams and I hope that you learn something with our lectures.