April 18, 2008

The Four Fast Acting Insulins Have Different Activity Curves

Fasting acting insulin is the insulin you inject to cover the rise in your blood sugar that occurs after you eat a meal.

They are called "fast acting" because unlike the basal insulins, Lantus and Levemir, they are absorbed relatively quickly after injection. This is what makes it possible to use these fast acting insulins to cover a meal.

In theory, if you can figure out how many grams of carbohydrate one unit of fast acting insulin will cover, and if you can figure out how to estimate the number of grams of carbohydrate on your plate, you can match the insulin to the meal and get normal blood sugars.

In practice this is harder than it sounds. It's tough to figure out how many grams of carb one unit will cover, especially since this amount may be different at different times of day. It is also hard to estimate how many grams of carbohydrate are actually on your plate. We'll discuss both these issues in some future blog posting.

What I want to discuss here is the speed and duration with which each of the fast acting insulins acts. This is what is called its "Activity Curve." The most important qualities of the activity curve are:

1. When the insulin reaches its fullest strength. This is also known as when the insulin "peaks." Ideally you would like the insulin to peak at the time when the carbohydrates from your meal hit your blood stream. That way most of the insulin meets most of the carbs.

2. How long the insulin stays active. Because insulin is being absorbed from the subcutaneous fat into which you injected it, it isn't all absorbed at once, so it typically takes anywhere from three to eight hours for the complete dose of a fast acting insulin to be used up.

When you get a vial or pen full of insulin, it will usually include the Prescribing Information for the insulin and that prescribing information will included a set of graphs that purport to show the activity curve for that particular insulin when used by people with Type 1 and by people with Type 2 diabetes.

What the insert does NOT tell you is that the curve you see is the average activity curve for the insulin. In fact, each of us will have our own unique response to each of the insulins and these responses can be quite different from what you see on that graph in the Prescribing Information.

Our own unique activity curve will vary depending on how large a dose we inject, how much fat we have, how much scar tissue we have at injection sites, and unique features of our metabolism that are not yet understood.

What this means in practice is that a fast acting insulin that works very well for you may work poorly for me--and vice versa. Whether a specific fast acting insulin will work well for you is something you can only determine by testing it out.

I've used all four of the fast acting insulins and while I could report on how they work for me, I won't, because my personal response to the insulin is not going to tell you much about what your response might be. Instead I'll just summarize a bit about each of the insulins so that if you want to explore using one with your doctor you'll have an idea of the range of experiences people have with these insulins.

1. Regular Human Insulin. Sold under the brand names Humulin R and Novalin R this insulin has the identical make up to the stuff your body makes. Because your body dumps this kind of insulin right into your circulatory system, it isn't designed to be absorbed from fat and thus when injected it absorbs into the blood stream relatively slowly. This is not necessarily a bad thing.

Most people report that they must inject R insulin from between 45 minutes to 1 hour before eating and that it stays active for the next 4-8 hours, depending on the size of the dose. The bigger the dose, the longer it stays active. However it usually peaks between 2 and 3 hours after injection and when used in small doses (5 units e.g.) it is usually finished acting by five hours. If you are eating a fairly low carb diet or one rich in fibrous, slow-digesting carbohydrates, this may a very good insulin to use because its long slow curve is more likely to match the pattern of your rising blood sugar after a meal.

R is also a very good insulin for people who are prone to hypo, because it is much slower in its action so you get more of a warning period as blood sugars drop before you go really low. Because of its slower speed--it may stay active for up to 8 hours, it may have a bit of a residual effect that will lower fasting blood sugar the next day. This is not true of any of the other, faster, insulins.

The final advantage of R is that it is much, much cheaper than the other insulins we'll discuss. You can buy it at Wal-Mart for about $22 a vial. Everywhere else it is about $36 a vial. You do not need a prescription to buy R insulin (though you may need one for the needles.)

2. Humalog. This is Lilly's fast acting insulin and it is the one that most people seem to start out using when their doctors prescribe fast acting insulin. Many people find that Humalog works well if they inject no more than 15 minutes before eating. Some can inject it right before eating.

Humalog should peak about 1 hour after injection and it is supposed to stay active for about three hours. Dr. Bernstein says that you should use 1/3 less of a dose of Humalog than you would use for R. Though many people find this the ideal insulin to use, a few report that it causes a pattern of highs at one hour followed by lows at three hours when they inject it as directed.

3. Novolog. This is Novo-Nordisk's fast acting insulin. If you are having problems with Humalog, it is well worth a try. Novolog is also injected no more than 15 minutes before eating and it peaks one hour after injection. It too should be done by 3 hours. It can be dosed identically to R insulin.

4. Apidra.This is Sanofi-Aventis's fast acting insulin. It is the newest of the fast acting insulins. It is a bit faster than either Humalog or Novolog and many people (self included) find it can be injected at the time of eating or even after eating and work very well. However, it also clears out of the body faster than the other insulins, which can mean that if you have slower digesting carbohydrates in your meal, the insulin my be finished before the carbs get into your blood stream. If this is an issue, you can split your doses and use two shots if you have eaten something like Pizza that you know will cause a delayed spike.

Apidra is not available yet in the U.S. in a disposable pen, though a version in the Solostar disposable pen is currently available in Europe. In the U.S. it currently comes in either a vial or cartridges which you can use with the Opticlik pen. The problem with this pen is that you can only get it from your doctor, so if you lose it or it goes bad on a weekend or when your doctor doesn't have any more, you can be SOL. Plus it is enormous.

Changes in Your Response to a Specific Insulin. After using fast acting insulin for several years, I've learned that my body's response to a particular insulin may change over time. It may work very well for a while and then the timing will start to change. There are several reasons for this:

1. Insulin can go bad. If you are carrying around a pen in your purse in the summer, for example, the heat can kill the insulin or if the exposure is borderline, weaken it. So can a lot of bouncing around. Leaving it in a car too long can also weaken it. You can also kill insulin by putting it in the butter compartment of your fridge door if the door is full of stuff that jiggles when you open and shut the door. Insulin does not like being vibrated. Finally if your fridge is too cold, it can freeze your insulin.

2. You can develop antibodies. Injecting things into your skin is a great way to get your immune system riled up, and over time many of us develop antibodies that attack the insulin proteins we inject. This can make the insulin behave unpredictably. Sometimes all you need to do is to switch to a different kind of fast acting insulin. Alternatively, you may have to use more and change the timing.

3. Random Factors. Your activity level, the temperature outside, infection, etc can all change how your body responds to a specific fast acting insulin.

If there is one thing I've learned using insulin these past couple years it is that any time I get things set up just right, something changes. This is probably the toughest part of using insulin. The books make it sound pretty cut and dried, and there is a certain amount that you learn that doesn't change, but using insulin to get normal blood sugars requires an ongoing process of continual small adjustments.

What Dose to Use?

I include this question here because I see people posting it all over the internet. The answer is "The one that is right for you." And figuring that out can take time. The dose of fast acting insulin that will cover 20 grams of carbohydrate may range from 1 unit to 20 units. It depends on how insulin resistant you are. That is something you can only learn by starting with a very low dose and slowly raising it until you see an impact.

And to answer the other question I get asked a lot, No. It is not possible to estimate how insulin resistant you are from any lab test, no matter what the doctors tell you. Nor does your weight tell how insulin resistant you are either. You'll just have to inject a very small dose of insulin when eating a meal containing a known amount of carbohydrate and see what happens next, and work up from there.


Anonymous said...

Jenny--You state:

Sold under the brand names Humulin R and Novalin R this insulin has the identical make up to the stuff your body makes.

Can you directed me to a scientific citation that proves this claim?


The Old Man and His Dog said...

Again your blog is the only place to get this kind of info...thanks for everything.

I just ordered your book from Amazon and can't wait for it to get here. For less than $20 I'll get more information on diabetes than I've received from thousands of dollars spent on almost 50 Dr. visits over a 13 year period!

Jenny said...


The description of the molecular make up of R insulin is in the prescribing information.

The controversy about injected insulin which you may be thinking about has to do with the absence of C-peptide in injected insulin. C-peptide, however, is not a part of the actual insulin molecule. C-peptide is a byproduct of an intermediate stage of the process by which insulin is synthesized in the body.

Some people believe that C-peptide may have some health benefits of its own and are lobbying for it to be included with insulin. But it is a separate protein and not a part of the human insulin molecule which is used to move glucose into cells.

Old man & his dog,

Thanks for the very kind words. I hope you like the book!

Anonymous said...

I ask for a couple of reasons (neither of them related to C-peptide.) The NDA for Human Insulin contained the following statement in the approval summary:

“When these assay methods become compendial, compliance will be required.” To my knowledge, this has been successfully ignored, and remains unaddressed.

Apparently, ‘assay methods’ have not yet (more than 20 years later) become compendial . . . and consequently, unknown and unknowable numbers of diabetics have used this product based on the unproven (and possibly false) premise put forth by the insulin manufacturer: "It's just like the human body makes."

Westpharma.com offers this explanation of compendial: "Compendial tests are performed to determine if the material's specifications are met and/or to address anticipated regulatory concerns. These test series can also be applied to determine general drug compatibility or for routine quality control"

The ingredients have been tested (compendial test) and they are recognized in official pharmacopeia and meet specific quality standards.

In my opinion, then, for more than 20 years, diabetics have been 'consumer units' for insulin manufacturers, injecting themselves with a product that may be "similar" to what the human body makes--but not necessarily. We DO know that it lowers bG; we DO know that increased incidence of hypoglycemia unawareness was noted in pre-approval clinical trials. We DO know that a percentage of users experience immunogenic response to this product--even though it is "just like the human body makes."

rDNA human insulin—to this day—has not been proven to be identical to human insulin. It may have the same atomic weight (Daltons). It may perform biologically in a manner consistent with natural insulin. But it relies on an unprovable assumption: E coli technology creates an A chain and B chain; transcription joins these two chains to form an insulin or insulin-like molecule. It is ASSUMED—but cannot be proven—that transcription produces a spatially-perfect configuration.

In other words, for more than 20 years, insulin-dependent diabetics have unquestioningly, unknowingly, or unwillingly served as real-time guinea pigs for insulin manufacturers. We can only ASSUME that Humulin and Novalin are "just like the human body makes." We can ASSUME that no harm is caused by the genetic-engineering technology, itself. We can ASSUME that human insulin is better than natural animal insulin because we have been TOLD that it is.

Dr. Arthur Teuscher, a Swiss diabetologist, in his book, “Insulin: A Voice for Choice”, has stated emphatically that synthetic human insulin is NOT just like human insulin. Does he know something we don’t? And if so, why?


Unknown said...

thank you. great info. to use in addition to other factors.

for me, humalog was like injecting water. garbage, didn't do anything to me at all, and nothing to my blood sugars...i even tried to double (recommended to do 1/3 of a regular injection) what Humalin R dosage i normally take, and nothing...

each person will have different reactions.