Dr. Pillion Diabetes Mellitus, Part 2 Page 1 of 7

H&E: 11:00 - 12:00Scribe: Marjorie O’Neil

Friday, November 13, 2009Proof: Caitlin Cox

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.

Using the Exubera inhaler [21]:
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.
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]:
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.
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.
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.
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.
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]:
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]:
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.
***AUDIO WENT OUT HERE. IT PICKED BACK UP ON SLIDE #34. Notes below are the ones I took***
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]:
There are premixed insulins available.
To approach therapy:
An adjustable pen (adjustable dosages) can be used.
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…
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…
The other piece of equipment they will need to have with them is the glucose meter.
Each time you take insulin, blood sugar needs to be checked first.
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.
If blood sugar is 50, you probably need to take less insulin.
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.
NPH/Regular- Available as 70/30 (7 parts NPH/ 3 parts regular) or as 50/50.
NPL/Insulin lispro - Available as 75/25 and 50/50
NPA/Insulin Aspart- Available as 70/30
Cloudy solutions, neutral pH
Advantages of Pre-Mixed Rapid/intermediate insulins [26]: skipped, but here is the info from the slide:
Convenience and mixing accuracy of a premixed insulin.
Unique rapid onset of action of insulin.
Injection closer to mealtime, anytime within 15 minutes before a meal
More physiologic insulin profile.
Today [27]:
Another approach is the insulin pump.
Use the Basal Bolus approach-
In the future is a glucose meter and insulin pump may be combined.
The upside is that you don’t have to make the decision on how much insulin to take. But this is a trade-off.
It is almost like you are a type 2 diabetic.
What changed everything about treating type 1? [28]:
Glucose self-monitoring & HbA1c analysis.
Glucose Self-Monitoring [29]:
Faster testing, less blood, less pain, alternate sites, noninvasive testing, continuous glucose monitoring.
In the future, non invasive testing.
A1C and Self-Monitoring Results [30]:
From Wikipedia:
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.
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.
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.
5.5% would be a nice number for a non-diabetic person.
7% would be a number for someone with diabetes.
If we tested African American females over the age of 50, currently …
This only takes about 7 min and costs about 20 dollars.
Patient Education Issues [31]:
Need to know about administering insulin, when to self-monitor blood glucose.
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.
Insulin administration-
Abdomen preferred injection site
Fast-acting insulin bolus within 15 minutes before meals
Regular insulin 30–45 minutes before meals
When to self-monitor blood glucose-
4 times per day (pre-meals)
Occasionally 1–2 hours post meal
Occasionally at 3:00 a.m.
How to recognize and treat hypoglycemia and hyperglycemia.
Tomorrow: many options! [32]:
The treatment with organ rejection consists of cyclosporins and prednisone.
Treatment of organ transplant is more dangerous than treatment of diabetes for children.
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.
Glucagon [33]:
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.
Additional facts about Diabetes [34]: ***Audio picks back up in the middle of this slide***
We talked about Cloudy insulin.
DCCT- was a diabetes with complications trial. With lower blood sugar, they had fewer complications.
Conclusions: lower blood sugar is a good thing and high blood sugar is a bad thing
Diabetic ketoacidosis
Gingivitis- this is much more common in people with diabetes.
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 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.
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.
We recognize that retinopathy, glaucoma, cataracts, and gingivitis all occur with greater frequency among people with diabetes.
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.
You should at least recognize that inflammation and blood sugar go hand in hand together.
Diabetes Part II [35]:
We will now talk about type 2 diabetes and the drugs used to treat it.
Treating and Curing Type 2 [S36]:
Skipped.
Identifying the problem, changing the way we live, using drugs, using surgery.
The shape of things to come [S37]:
We are the fat person at the front in the 21st century.
Minorities at greater risk [S38] :
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.
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).
Increasing prevalence of obesity in US adults [S39]:
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%.
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.
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.
Increasing prevalence of diagnosed diabetes in US adults [S40]:
Here is diabetes and you can see a parallel from the information in the slide above.
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.
How many people in AL have Diabetes Mellitus? [S41]:
How many people in Alabama have diabetes? We have about 4 million people and 10% of them have diabetes, so about 400,000.
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.
We may have as many as 1.2 million pre-diabetics in Alabama, or 30% of our population is pre-diabetic.
Alabama map [S42]:
Where are the diabetics in Alabama found?
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 optometrists, relative to the distribution of people with diabetes? There are not many practitioners where the folks are with diabetes.
AL maps [S43]:
Here is the distribution of endocrinologists on the left and diabetes educators on the right. Each dot represents an individual.
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.
Pre-diabetes [S44]:
Pre-diabetes can be defined as impaired fasting glucose or impaired glucose tolerance.
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.
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.
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.
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.