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Dr. Pillion
Diabetes Mellitus, part 2
Page 1 of 7
The audio was missing starting half way through slide 24 and picking back up in the middle of slide 34. I have
included my notes from class (not promising they are right) and notes that were included on those slides.
I.
II.
III.
IV.
V.
VI.
Using the Exubera inhaler [21]:
a. There is another inhaled insulin that is being made, you will probably see it out on the market about a year from
now but it won’t be called exubera. It will be a pulmonary form of insulin delivery.
b. There is hope for the future for oral insulin, transdermal insulin, and nasal insulin. As you progress in your
career, you will find alternate routes of delivery. There will also probably be alternate routes of delivery for
glucagon; a nasal spray and an oral one are in development now.
Preserving structure-function relationships[22]:
a. Here is the insulin molecule. The modification for Glargine is to put some amino acids at the end that make it
precipitate. Detemir is different because they put a lipid tail on the back of it. This modification is being utilized
by not just insulin but companies are using this strategy for a couple of other drugs as well.
b. If you put a lipid tail on a protein molecule, what will it do to its chemistry and the way it behaves in the
bloodstream? Insulin is a nice, charged, water soluble molecule but if you put a lipid tail on it, that lipid tail
makes it much less water soluble. This makes it more likely to bind to albumin which will make its life
expectancy in the bloodstream go up. When it gets to the kidney, it won’t be filtered and it won’t be cleared.
That is why this form of insulin has a much longer half life than normal insulin does.
c. A lot of other drugs that are out there that are peptides such as GH and others, they may also end up going
down the same pathway- have lipid tails attached, bind to albumin and have much longer half lives.
d. By modifying the length of the lipid tail, they are optimizing the kinetics. They started with 6 carbons, then 8
carbons, then 10, then 12, 14, 16, 18, and all the way to 20 carbons to see which one gives the best
pharmacokinetic profile. The longer the lipid tail is the longer the half life.
e. You can design drugs based on a change in that lipid tail to tailor it to how long you want a drug to work.
Insulin detemir [23]:
a. They use a C-14 fatty acid on the tail of this molecule to make it work that way.
Mixing Regular and NPH Insulins [24]:
a. You can mix regular and NPH in vials. Doing it by hand is tedious. You have to avoid contamination. Regular
insulin is clear, NPH insulin is cloudy. If you get the cloudy insulin into the clear insulin by mistake, it makes it a
more long lasting form of insulin (slowing it down) so then if you use it in the future for a faster action, you
actually end up slowing its course of action down. You try to avoid that.
b. ***AUDIO WENT OUT HERE. IT PICKED BACK UP ON SLIDE #34. Notes below are the ones I took***
c. The other thing to consider is that sometimes people will leave their insulin in their pocket. In the summer the
insulin will get cloudy if it gets hot (if it was left in the car or if it was in their pocket and they were outside a
while). When it turns cloudy, it is inactivated. The people take the cloudy insulin not knowing it has changed
and their blood sugars get higher and they don’t know why because they are taking their insulin. You should
ask them if their insulin is clear or cloudy and make them aware.
Pre-Mixed Insulins [25]:
a. There are premixed insulins available.
b. To approach therapy:
i. An adjustable pen (adjustable dosages) can be used.
ii. What kind of insulin should it be? The answer is it depends. If you are going to use this by itself (with
nothing else), then the fast acting insulin…
iii. One of these mixtures would be a better way to go. If you get a shot of this with each meal you will get a
rapid acting…
c. The other piece of equipment they will need to have with them is the glucose meter.
d. Each time you take insulin, blood sugar needs to be checked first.
i. If I sit down at lunch and don’t know how much insulin to take, you must look at the contents of the meal
and check your blood sugar and determine the appropriate amount of insulin.
ii. If blood sugar is 50, you probably need to take less insulin.
iii. Imagine that type of calculation in a 4 year old or 6 year old. It is a lot of responsibility, and the parents
have to help.
e. NPH/Regular- Available as 70/30 (7 parts NPH/ 3 parts regular) or as 50/50.
f. NPL/Insulin lispro - Available as 75/25 and 50/50
g. NPA/Insulin Aspart- Available as 70/30
h. Cloudy solutions, neutral pH
Advantages of Pre-Mixed Rapid/intermediate insulins [26]: skipped, but here is the info from the slide:
a. Convenience and mixing accuracy of a premixed insulin.
b. Unique rapid onset of action of insulin.
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Dr. Pillion
Diabetes Mellitus, part 2
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c. Injection closer to mealtime, anytime within 15 minutes before a meal
d. More physiologic insulin profile.
VII. Today [27]:
a. Another approach is the insulin pump.
b. Use the Basal Bolus approachc. In the future is a glucose meter and insulin pump may be combined.
d. The upside is that you don’t have to make the decision on how much insulin to take. But this is a trade-off.
e. It is almost like you are a type 2 diabetic.
VIII. What changed everything about treating type 1? [28]:
a. Glucose self-monitoring & HbA1c analysis.
IX. Glucose Self-Monitoring [29]:
a. Faster testing, less blood, less pain, alternate sites, noninvasive testing, continuous glucose monitoring.
b. In the future, non invasive testing.
X. A1C and Self-Monitoring Results [30]:
a. From Wikipedia:
i. Glycated hemoglobin (Hb A1c) is a form of hemoglobin used primarily to identify the average plasma
glucose concentration over prolonged periods of time. It is formed by Hb’s normal exposure to high plasma
levels of glucose. Glycation of hemoglobin has been implicated in nephropathy and retinopathy in diabetes
mellitus. Monitoring the HbA1c in type 1 diabetic patients may improve treatment.
b. As your blood sugar goes up, more of your A1’s get glycosylated. He said this will be a test question: A1c tells
you how much glucose is attached to A1 hemoglobin.
c. If I take a blood specimen from my finger tip right now, it will contain RBC’s. 120 days is the life expectancy of a
RBC, so the specimen you take will contain RBCs of all different “ages” (new ones, middle-aged ones, and older
ones). A1C reflects the glucose levels from the past 3 months.
d. 5.5% would be a nice number for a non-diabetic person.
e. 7% would be a number for someone with diabetes.
f. If we tested African American females over the age of 50, currently …
g. This only takes about 7 min and costs about 20 dollars.
XI. Patient Education Issues [31]:
a. Need to know about administering insulin, when to self-monitor blood glucose.
b. Glycemic index measures how fast that food makes your blood sugar go up. He then gave the glycemic index
for table sugar and candy bars. Plain glucose has a higher glycemic index than sucrose.
c. Insulin administrationi. Abdomen preferred injection site
ii. Fast-acting insulin bolus within 15 minutes before meals
iii. Regular insulin 30–45 minutes before meals
d. When to self-monitor blood glucosei. 4 times per day (pre-meals)
ii. Occasionally 1–2 hours post meal
iii. Occasionally at 3:00 a.m.
e. How to recognize and treat hypoglycemia and hyperglycemia.
XII. Tomorrow: many options! [32]:
a. The treatment with organ rejection consists of cyclosporins and prednisone.
b. Treatment of organ transplant is more dangerous than treatment of diabetes for children.
c. In the future, you may see three or more puffs of nose drops a day plus one shot of glargine or an insulin pump
or transplanted islet cells or transdermal insulin or oral insulin.
XIII. Glucagon [33]:
a. Glucagon we talked about: It is a peptide hormone that is made in the pancreas. It is secreted when blood
glucose level becomes too low. It is used clinically to rescue patient with severe hypoglycemia.
XIV.
Additional facts about Diabetes [34]: ***Audio picks back up in the middle of this slide***
a. We talked about Cloudy insulin.
b. DCCT- was a diabetes with complications trial. With lower blood sugar, they had fewer complications.
i. Conclusions: lower blood sugar is a good thing and high blood sugar is a bad thing
c. Diabetic ketoacidosis
d. Gingivitis- this is much more common in people with diabetes.
i. Gingivitis: what does it do to your blood sugar? It is an infection, so what do infections do to your blood
sugar? It increases blood sugar. If someone takes insulin for their diabetes and gets the flu or a stomach
virus and they throw up and don’t eat lunch, should they or shouldn’t they take their insulin? Should they
take zero, same, or more insulin than they take on a normal day? (this could be a *TQ*) More insulin on
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Diabetes Mellitus, part 2
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an empty stomach is the answer. This is because an infection is ramping out a lot of cortisol, and they are
putting out a lot of glucose. If you were to check their blood sugar, despite the fact that they didn’t eat
lunch, their blood sugar might be 300, 400, or 500. If they don’t take insulin, they will get diabetic
ketoacidosis. This is actually one of the leading causes of diabetic ketoacidosis (the patient thinks they
don’t have to take their insulin when they haven’t eaten food). You should remember that when you are
sick, you’re blood sugar goes high. When you throw up and get dehydrated, your blood sugar gets more
concentrated and you are also pumping out a lot of cortisol, therefore you need to take insulin and probably
have to take more insulin. You should take your blood sugar levels more often on days like that (5-8 times)
to keep track of how your blood sugars are doing.
ii. We know that people with diabetes get more gingivitis, but he wants to ask: do the people who get
gingivitis have more diabetes? People with gingivitis have high glucose in response to the chronic
infection. There are a few case reports where people have pulled out all of their teeth to clear the infection,
and these people’s diabetes went away. The theory was that when you pull out the teeth, you eliminate the
infection and that additional burden on the glucose homeostasis is taken away and the blood sugar that
was too high came back down closer to normal.
e. We recognize that retinopathy, glaucoma, cataracts, and gingivitis all occur with greater frequency among
people with diabetes.
f. There are things now that indicate that maybe diabetes is a state of chronic inflammation or that a state or
chronic inflammation causes diabetes. The inflammation pathway drives up blood sugar. The thought is that if
you can get rid of the chronic inflammation you can get rid of the diabetes.
g. You should at least recognize that inflammation and blood sugar go hand in hand together.
XV. Diabetes Part II [35]:
a. We will now talk about type 2 diabetes and the drugs used to treat it.
XVI.
Treating and Curing Type 2 [S36]:
a. Skipped.
b. Identifying the problem, changing the way we live, using drugs, using surgery.
XVII. The shape of things to come [S37]:
a. We are the fat person at the front in the 21st century.
XVIII. Minorities at greater risk [S38] :
a. Minorities are at a greater risk. African Americans, Hispanics, and Native Americans have a higher incidence of
type 2 diabetes. Caucasians have a higher incidence of type 1 diabetes. We don’t know why.
b. Native Americans for thousands of years were living on a very modest diet and therefore their bodies were
adapted to starvation periods. When they were introduced to McDonalds and unlimited supplies of food, they
turned into bowling balls. (Here the audio skipped to the next slide but he was saying something about the
incidence of type 2 diabetes in Native Americans).
XIX.
Increasing prevalence of obesity in US adults [S39]:
a. Here are the charts that people show. These are color coded for obesity in 1991 vs 2001. Alabama in 1991
was a blue state which means that 10-14% of our population were obese. Then in 2001 we turned into a bright
yellow state, where 20-24% of our population were obese (although this is the number he said in class, based
on the color coding on the slide AL was >25% in 2001). So in 10 years we jumped from 10-14% to 20-24%.
b. Is that increase typical for most disease states in our country? For example- breast cancer, colon cancer, HIV,
etc, do any of those go up like that in 10 years? No.
c. Obesity is an epidemic. Obesity now is driving an increase in the number of cancer deaths and cardiac deaths
and a number of other processes that are associated with obesity.
XX. Increasing prevalence of diagnosed diabetes in US adults [S40]:
a. Here is diabetes and you can see a parallel from the information in the slide above.
b. In 1991, Alabama had 4-6% of the population with diabetes, and in 2001, greater than 10% of the population of
Alabama has diabetes. These numbers since ’01 have gotten progressively worse.
XXI.
How many people in AL have Diabetes Mellitus? [S41]:
a. How many people in Alabama have diabetes? We have about 4 million people and 10% of them have
diabetes, so about 400,000.
b. We have probably 50% of that who have undiagnosed diabetes, and pre-diabetes has been estimated to be
about three times as many as those pre-diabetics.
c. We may have as many as 1.2 million pre-diabetics in Alabama, or 30% of our population is pre-diabetic.
XXII. Alabama map [S42]:
a. Where are the diabetics in Alabama found?
b. This shows the distribution of diabetics in the state. The black belt, where there is a high concentration of
African Americans, a high incidence of obesity, and a high incidence of type 2 diabetes. How does this pile into
your practices? What do you think about the distribution of clinicians and diabetes educators, dentists and
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Diabetes Mellitus, part 2
Page 4 of 7
optometrists, relative to the distribution of people with diabetes? There are not many practitioners where the
folks are with diabetes.
XXIII. AL maps [S43]:
a. Here is the distribution of endocrinologists on the left and diabetes educators on the right. Each dot represents
an individual.
b. There are zero endocrinologists near the middle of the state and there are only 1 or 2 diabetes educators
scattered throughout there. There are a lot in Jefferson County. We have a mismatch of where the people are
that have diabetes and where the clinicians are to treat them. Most of the people with diabetes get treated by a
general practice doc in the box who is not skilled or not up to date in diabetes care because diabetes care has
transitioned over the last 10 years into using drugs and devices and approaches that weren’t there 10 years
ago. What they learned 10 years ago in diabetes care is obsolete today and 10 years from now what we
learned today will be obsolete.
XXIV. Pre-diabetes [S44]:
a. Pre-diabetes can be defined as impaired fasting glucose or impaired glucose tolerance.
b. Impaired fasting glucose- this means that if you measure your glucose in a fasting state, it is impaired. If you
test someone right when they wake up, they should be less than 100 mg/dL. If they are between100-126, then
they’ve got impaired fasting glucose. Fasting blood sugar greater than 126 means that you have diabetes (this
is one definition of diabetes). The trouble with that definition is that not all diabetics will give you a fasting blood
sugar above 126, so you have some people with type 1 diabetes who will have a fasting blood sugar in the
morning of 120. They do have diabetes, because this definition is not all inclusive. But if it is more than 126,
they have diabetes, which is one of the ways you can diagnose it.
c. Impaired glucose tolerance- this tells you that you can take a glucose tolerance test (commonly this test is given
during pregnancy). You give someone a 75 gram carbohydrate drink; you check their blood sugar after they
drink it 30, 60, and 120 minutes later. 120 minutes later their blood sugar should be below 140. If it is between
140 and 199, they have impaired glucose tolerance (which is another way of saying pre-diabetes). If they are
above 200, then they have diabetes. So this is the second type of test. Some diabetics you pick up with this
test and others you pick up with the other test, but you don’t pick up all diabetics with either test. Therefore you
will miss some people if you only do one test without the other.
d. Many pregnant women in their third trimester, when they are given a glucose tolerance test, will become
temporarily diabetic. They will have gestational diabetes. They will fall into the range where we would say you
have diabetes. After delivery, the burden on their body is reduced and now their blood sugar will come back
down into the non-diabetic range. Sometimes it only comes back down to the pre-diabetic range which tells us
that their pancreas can carry the load when things are going well but when a burden is placed on them they
can’t always keep their blood sugar in control.
e. If a woman has delivered a baby that is over 9 lbs that should be a red flag that she probably had gestational
diabetes, and she should be tested for diabetes later in life. Many times as that person gets older, their
pancreas function will go downhill and it will reach a point where they become diabetic.
f. People in the pre-diabetic range that get an illness will have to go to the bathroom a lot. They will temporarily
have a high blood sugar, and when the illness resolves itself the blood sugar comes back down to normal range.
XXV. Are more children getting Type 2 diabetes mellitus? If so, why? [S45]:
a. Yes.
XXVI. What schools have done differently [S46]:
a. They have gotten rid of P.E. classes, serve high-fat lunches, and put in soda machines and snack machines.
XXVII. Cartoon [S47]:
a. We have 50% less fat in our fries now, so this guy buys two fries.
b. Some people have the logic that since something has less fat they can eat more of it.
XXVIII. Cartoon [S48]:
a. Well rounded students. In the state of Alabama, we have worked to get the soda machines out of the schools,
so as a compromise we left soda machines in the schools that sell water. Schools make so much money from
soda machines, so they resisted us trying to take them out of schools. The compromise was to sell water and
that way coca-cola is happy and the schools are happy.
XXIX. Case Study [S49]:
a. This is a 17 y.o. lady that weighs 167 kg. Her BMI is 65. A BMI under 25 is normal, 25-29 is overweight, and
above 30 is obese.
b. You can see that her other symptoms (morbid obesity, sleep apnea, orthopedic complaints) make sense.
Walking puts a tremendous burden on her knees, hips, and ankles, and so putting her into an exercise program
is quite a challenge.
c. She has failed medical treatment for 4 years, so now she is a candidate for bariatric surgery. This is where they
go in, cut the intestinal tract, reconnect it, and have a much smaller amount of both the stomach and intestines
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Dr. Pillion
Diabetes Mellitus, part 2
Page 5 of 7
available for food capacity so that food capacity will get diminished. Her stomach could go from the size of a
football to the size of a tennis ball. Anything greater than what would fill up a tennis ball would cause her to
throw up. This is the approach that is used for a lot of people with morbid obesity and type 2 diabetes. It is
controversial because it is expensive (costs about $40,000), and it does have a mortality of about 1%. The
surgeons would argue that the interventionists are unsuccessful; the alternative for this young lady is a life of
obesity, depression, orthopedic problems, heart attack, stroke, and early death. It is always a debate on
whether or not a person is a good candidate for bariatric surgery.
d. Obstructive sleep apnea is being recognized now as a big problem in folks who have morbid obesity.
e. Polycystic ovary syndrome (PCOS) / hyperinsulinemia is a major cause of infertility in people that are obese.
XXX. Obstructive Sleep Apnea: possible signs and symptoms
[S50]:
a. Here is another case. She is 5 years old, 150 lbs. She has obesity, snoring, daytime sleepiness, bedwetting,
headaches, and poor school performance.
b. If you are trying to set up a scenario where someone would be unsuccessful in life, you would have them be 5
years old and 150 lbs. Depression, bedwetting, poor sleep, poor school performance, low self esteem and a
future that is filled with medical problems.
c. Is she a good candidate for bariatric surgery? Obviously we are getting to a gray area and in some cases you
do and some cases you don’t. More than likely, she won’t respond very successfully to pharmacologic
intervention. She will be challenged in terms of the medications that we provide her with, whether it be insulin or
oral hyperglycemic drugs.
XXXI. Medications that we have available [S51]:
a. Insulin we’ve talked about.
b. We have four classes of drugs here that we need to familiarize ourselves with for test purposes. For test
purposes, I want you to be able to match the drugs with what they do (mechanism of action).
XXXII. Oral Agents [S52-53]:
a. The first class to know is the Sulfonylureas.
i. They stimulate insulin secretion from the pancreatic beta cells.
ii. In what kind of a person would sulfonylureas work?
1. They do not work in people with type 1 diabetes whose pancreas is nonfunctional. ***TQ
2. They do work in people with type 2 who are early in the disease who have a pancreas that makes
insulin. If their pancreas has gotten old and dysfunctional, they won’t be very effective.
iii. What would be a side effect of someone who took too much of a sulfonylurea drug? Low blood sugar, they
would produce too much insulin. These people also tend to gain weight because insulin tends to increase
our ability to store calories. Side effects of sulfonylureas are hypoglycemia and weight gain.
iv. 10 years ago, a type 2 diabetic would have been given a sulfonylurea because it was inexpensive, made
blood sugar come down, and it worked for 3-8 years before it became ineffective. It becomes ineffective
because their pancreas went downhill and you are giving them a drug that makes your pancreas work even
harder. We think now that we may actually speed up the process of their pancreas getting worn out by
giving that class of drugs. They get used because they are cheap and oral and they’ve been around for a
long time. When it became ineffective, they moved onto the next drug (metformin, a biguanide).
b. Meglitinides
i. These are basically a fast acting version of these drugs, but they have a different chemistry. Think of the
meglitinides as fast acting sulfonylureas. You take them with the meal and you get a boost of how much
insulin you secrete.
c. Biguanides
i. These are the most widely used drugs in America for type 2 diabetes.
ii. Today in most practices, someone with type 2 diabetes would be given metfomin instead of sulfonylureas.
iii. Metformin doesn’t work at the pancreas, it works at the liver. It reduces the amount of glucose that the liver
puts out. The liver is an important player in diabetes. Metformin is an effective oral drug that reduces liver
glucose. It is more expensive but is widely used. This can also be used in combination with other drugs.
d. Thiazolidinediones
i. Improve peripheral insulin sensitivity; these work at fat cells and skeletal muscle cells to improve glucose
uptake.
ii. Now we’ve talked about 3 different drugs that work at 3 different organs which means they could be piled
on top of each other for an additive effect. If we give one drug that works at pancreas, one that works at
the liver, and one that works at the fat cells and skeletal muscle and put them together, we get additive
effects. Now companies are making combination pills where they put two of these together and someday
they will probably put three of these together.
iii. You can’t add together two drugs that do the same thing, but you can add together two drugs that work
different ways and get a combination pill that is more effective than either one alone would be.
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e. Alpha-glucosidase inhibitors
i. He did not talk about these.
***Dr. Pillion skips slides 54-62 but says to read them on our own so I have included the text from slides for you.
They give the side effects of the different drugs that we just talked about.
XXXIII. Sulfonylureas[S54]:
a. Sulfonylureas increase endogenous insulin secretion.
b. Other Effects: Hypoglycemia, Weight gain, No specific effect on plasma lipids or blood pressure.
c. Generally, the least expensive class of medication.
d. Medications in this Class[S55]:
i. First generation sulfonylureas: chlorpropamide, tolazamide, acetohexamide, tolbutamide
ii. Second generation sulfonylureas: Glyburide, Glimepiride, Glipizide
XXXIV. Meglitinides[S56]:
a. Meglitinides stimulate insulin secretion (rapidly and for a short duration) in the presence of glucose.
b. Other Effects: Hypoglycemia (although may be less than with sulfonylureas if patient has a variable eating
schedule), Weight gain, No significant effect on plasma lipid levels, Safe at higher levels of serum Cr than
sulfonylureas.
c. Medications in this Class: repaglinide, nateglinide
XXXV. Biguanides [S57]:
a. Biguanides decrease hepatic glucose production and increase insulin-mediated peripheral glucose uptake.
b. Other Effects: Diarrhea and abdominal discomfort, Lactic acidosis if improperly prescribed, Cause small
decrease in LDL and triglycerides, No specific effect on blood pressure, No weight gain with possible modest
weight loss, Contraindicated in patients with impaired renal function (Serum Cr > 1.4 mg/dL for women, or 1.5
mg/dL for men).
c. Medications in this class [S58]:
i. Metformin
ii. Metformin extended release
XXXVI. Thiazolidinediones [S59]:
a. Thiazolidinediones decrease insulin resistance by making muscle and adipose cells more sensitive to insulin.
They also suppress hepatic glucose production.
b. Other Effects: Weight gain, edema, Hypoglycemia (if taken with insulin or agents that stimulate insulin release).
c. Contraindicated in patients with abnormal liver function or CHF.
d. Improves HDL and triglycerides; LDL neutral
e. Medications in this Class:
i. Pioglitazone, rosiglitazone [troglitazone - taken off market due to liver toxicity]; FDA warning for early
cardiac death.
XXXVII. Alpha-glucosidase Inhibitors [S60]:
a. Alpha-glucosidase inhibitors block the enzymes that digest starches in the small intestine.
b. Other Effects: Flatulence or abdominal discomfort, No specific effect on lipids or blood pressure, No weight gain.
c. Contraindicated in patients with inflammatory bowel disease or cirrhosis.
d. Medications in this Class:
i. acarbose, miglitol
XXXVIII.
Combination Therapy for Type 2 Diabetes [S61]:
a. Fixed combination pills:
i. Sulfonylurea + Biguanide
1. Glyburide
+ Metformin - Glucovance
2. Glipizide
+ Metformin - Metaglip
ii. Thiazolidinedione + Biguanide
1. Rosiglitazone
+ Metformin - Avandamet
iii. Sulfonylurea + Thiazolidinedione
1. Glimeperide + Rosiglitazone - Avandaryl
XXXIX. Combinations: Oral Agents and Insulin [S62]:
a. Insulin plus:
i. Biguanides, Sulfonylureas, Thiazolidinediones, Alpha-glucosidase inhibitors
XL. New Drugs [S63]:
a. These are the ones that have just come on the market since last year. These are called incretin drugs.
Incretins come from internal organs that increase the amount of insulin that we secrete. Amylin is a natural
hormone that incretin is based on.
XLI.
Multihormonal Regulation of Glucose [S64]:
a. GlP1 is a natural hormone that the other drug we will talk about is based on.
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b. GLP1 (Glucagon-like peptide 1) comes from the gut, and amylin comes from the pancreas. When we eat food
the pancreas secretes amylin that tells the brain to stop eating. Also when we eat food, the gut secretes GLP-1
that tells the pancreas to make more amylin and make more insulin and it tells the brain we’ve got enough food,
stop eating.
c. People with type 1 diabetes don’t make amylin.
d. People with type 2 diabetes don’t make enough GLP1.
e. The theory is to give these new drugs to people and improve their blood sugar level (because of the pancreas
effects) but also improve their weight gain by telling their brains: you’re full, stop eating.
f. If I give someone an injection of amylin or GLP-1 before a meal, they will have the same feeling that you have
after Thanksgiving dinner, which is where you feel full and don’t want food. Give that drug to a person that is
overweight before they eat a meal, and they are going to eat less. These drugs have therefore been effective
weight loss drugs. They are also effective as anti-diabetic drugs.
g. These are based on natural chemicals. The natural chemicals have a very short half live, so the drugs we give
are analogs that have a longer half life.
XLII.
Amylin is co-secreted with insulin [S65]:
a. Here is amylin and insulin. They both get secreted together.
b. We just discovered amylin in the past 5 years even though we’ve been studying insulin for 60 years.
XLIII. Amylin [S66]:
a. The analog is called Pramlintide. It has a longer half life. It decreases hunger, decreases glucose after a meal,
and decreases glucagon release. It is taken by injection and it produces weight loss.
b. This is a beneficial side effect (and normally side effects are bad).
XLIV. [S67-68]: Skipped.
XLV. GLP-1 Modulates Numerous Functions in Humans [S69]:
a. This talks about the fact that GLP-1 is coming from his gut.
XLVI. Exenatide (Byetta) [S70]:
a. The drug is called exenatide, an analog of GLP 1. This slows down your stomach, it induces a feeling of
fullness, and it produces weight loss. You take this by injection before meals.
XLVII. Like other peptides… [S71]:
a. The new category of drugs that is just coming out is based on the fact that normally GLP-1 is broken down by an
enzyme (don’t need to know its name), but the new drug is an inhibitor of this enzyme and you can take it orally
(the other drugs you had to inject).
b. If you take an oral drug that inhibits this enzyme, the GLP-1 will last longer. It is like giving you GLP-1, but really
it is just letting your own GLP-1 live longer.
c. The advantage is now that you have a pill to take rather than an injection.
d. Sitagliptin is the name of that new drug.
XLVIII. To get around this problem… [S72]: Skipped.
XLIX. Barriers to insulin use: patient issues [S73]:
a. Why don’t people like to take insulin? They don’t like to inject, they don’t want to get a low blood sugar, and
they don’t want to gain weight.
L. Barriers to insulin use: patients and providers [S74]:
a. They think insulin makes their diabetes worse and that taking it is inconvenient.
LI. With all these oral drugs...[S75]:
a. What is the best way to treat type 2?
b. The doctors practicing today will tell you it is oral drugs. Dr. Pillion thinks that is wrong and that there is not a
single way, but that they are all important.
LII. There is no single best way [S76]:
a. Skipped.
LIII. A1C Goals [S77]:
a. Right now 64% of patients who are treated with type 2 diabetes have an A1C above 7%. Our success rate is
36% in treating type 2.
LIV.
A new way to treat Type 2? [S78]:
a. The old days were sulfonylurease, today it is metformin.
b. He thinks in the future it is going to be insulin. He thinks we should put all of the type 2 diabetics on insulin
therapy. It would give them better control, lower their incidence of complications, and ultimately lead to a longer
life. As our insulin delivery systems get better he thinks that this will be the way that more and more people
choose to go.
LV. Conclusions [S79]: Skipped.
[end 50 min]