What Do You Know About Regular Insulin?

Just how much do you actually know about your insulin? Sadly, I am sometimes frightened about just how little some people who should know better actually know about the synthetic hormone they are injecting into their (or their child's) body. Even more troubling, however, is that when I ask them some basic questions, I am told "Oh, our CDE never told us that."

There is some very rudimentary information that anyone who uses insulin (or gives it to their child) needs to know. For example, you should always check what your pharmacist has given you before using it. What do you need to look for? Simply stated: Brand, Type and Strength, and maybe expiration (although as Allie Beatty has reported, the amount of toxic preservatives in your insulin and the fact that a majority of insulin sold today was probably made over a year ago and was imported and shipped across the Atlantic does kind of mitigate this issue slightly).

Insulin Is NOT A Drug, It's A Hormone

For most people, insulin is a type of hormone replacement (although for others it is hormone supplementation). Insulin sold in the U.S. is 100% synthetic (not of natural origin; prepared or made artificially), and to add to the confusion, analogs are not even insulin. There are no long-term studies evaluating the long-term impact of insulin analogs, all we know about them is their immediate impact on blood glucose levels. You may know that insulin can vary by brand, but its easy to see when you've received Novo Nordisk Novolog instead of Lilly Humalog (although, in truth, the brand name doesn't mean that either of these companies actually made it ... see here for details). Yet many people remain blissfully (and naïvely) unaware of the "older" insulin varieties, and oblivious to the fact that the human body makes only one type of insulin: regular.

Regular insulin, when secreted directly into the bloodstream by pancreatic beta cells, has a glucose-lowering action which is measured in just minutes compared to subcutaneously injected insulin, which even in the case the shortest acting insulin analogs, is still measured in hours. The simple fact is that subcutaneous injection of insulin was practical and convenient, but insulin was never intended to be administered subcutaneously. Regular insulin literally has several thousand years of proven efficacy across almost all species of animals.

It is therefore no accident that regular insulin is still the ONLY type of insulin available via IV administration, and that people going in for surgery will only be given only regular (at least while on the operating table). People without diabetes do not have Lantus, Levemir, Humalog, Novolog/Novorapid, Apidra or 70/30 coursing through their veins. So at the very least, you should know that if for some reason all of the Humalog, Novolog/Novorapid or Apidra were to disappear tomorrow, you (or your child) could survive quite fine on regular, and no, it does not mean certain complications, either. Furthermore, a number of meta-analyses studies have proven conclusively that insulin analogs do not deliver superior glycemic control over regular, yet we all seem to use them. Why? I would also add that the gold standard for insulin trials has been baselined against regular, but today, drug companies are trying to convince the FDA to abandon that standard in favor of rapid-acting insulin analogs the benchmark. But this is not a diatribe about insulin analogs, its merely meant to educate people about the most basic information they should already know.

How Potent Is Your Insulin?

Beyond the insulin type, you also need to check the strength or potency. Failure to do so could be a disaster. Consider that on December 13, 2005, a patient named Keith Scofield visited a Wal-Mart pharmacy in Frederick, MD and ordered Humulin R (U-100). Instead, he was allegedly given Humulin R (U-500), which is only available by pescription and contains is five times the strength of the insulin he requested. He reportedly injected that insulin on December 20, 2005, lapsed into a diabetic coma, and sadly, died on January 2, 2006, according to a lawsuit filed by his family. (That suit was reportedly settled during mediation without admission of liability or fault from the pharmacy, which happened to be Wal-Mart, see here for details)

Just what is insulin strength/potency? Well, the American Diabetes Association's Diabetes Forecast 2008 Resource Guide reports that all insulins come dissolved or suspended in liquids, but the solutions have different strengths. The most commonly used strength in the United States is U-100. That means it has 100 units of insulin per milliliter (also referred to as cc for cubic centimeter, which is an equivalent amount) of fluid.

But U-100 insulin was only introduced in the U.S. back in 1973. Prior to that, insulin was sold in different strengths, including U-80 (80 units per milliliter) and U-40 formulations (40 units per milliliter), so there was an effort made to "standardize" the potency sold in the U.S. to reduce dosage errors and ease doctors' job of prescribing for patients. But standardization did not eliminate the possibility of error, that burden really falls on the consumer -- but some people aren't aware of that.

The ADA's Diabetes Forecast 2008 Resource Guide also reports that the other strength available is U-500 insulin, which is five times more concentrated than U-100 insulin and is used infrequently. This form of insulin is only for people with marked insulin resistance who require doses of more than 200 units of insulin per day. However, as the prevalance of type 2 diabetes has grown, the use of U-500 has too, and many pharmacies now carry it for customers. A simple mistake by a pharmacy tech (as opposed to a licensed pharmacist) could happen quite easily.

Finally, the ADA 2008 Resource Guide also also notes that because different syringes are used for different insulin strengths, it's also essential that your syringes match your insulin. For example, because the syringes are calibrated to match the insulin preparation, you would need to adjust the drawn up amount accordingly if you ever had to use a different strength or potency of insulin.

U-500, Check. U-40 ... Wasn't That Discontinued in the 1970's?

Its worth noting that U-40 insulin is still widely available in the U.S. as a treatment for animals (dogs and cats) with diabetes. U-40 means that there are 40 units of insulin per milliliter of fluid. Note that some large U.S. pharmacy chains, such as Walgreens and CVS will happily fill prescriptions for pet prescriptions and often at a better price than your veterinarian. And, contrary to what we've been led to believe, highly-purified bovine and porcine insulin is still made in the U.S.A. and sold legally in the U.S. today, only it is marketed towards veterinarians and is by and large, U-40 strength. While Walgreen's may not carry pet insulin in the store regularly, they can usually have it in a day or two. But the U-40 strength is also more common in some other countries outside the U.S., so at least be familiar with it.

While U-100 may be the defacto standard in the U.S. today, the fact is that U-40 and U-500 aren't unheard of. But you cannot simply use a U-100 syringe with another strength of insulin. Let's say a patient was on 20 units of NPH, and the only insulin available was U-40, then they could use a U-100 syringe but would need to draw up 0.5 cc rather than 0.2 cc. Similarly, if you needed 20 units of regular but received U-500 instead, you would need to reduce your dosage to one-fourth the size, or just 5 units.

Could Color Coding Help Avoid Mixups?

There has been an inconsistent effort to address the confusion by color-coding different strengths of insulin, but beyond discussions and submissions to the FDA, nothing has happened.

In 1996, when the FDA approved Humalog, the manufacturer (Eli Lilly and Company) used a different color of the crimp and cap on Humalog vials and cartridges (magenta) to distinguish the product from Regular (Humulin R) but others did not adopt the scheme.

The International Diabetes Federation again discussed the issue of color-coding back in 2004, but nothing further ever happened with it beyond the discussion. One issue is that some people are color-blind and cannot distinguish variations in colors, therefore the products must also have basic information for consumers to properly identify them, therefore there has not been big a rush to move ahead.

Then, in 2005, the FDA held a meeting and solicited public comment on the "Use of Color on Pharmaceutical Product Labels, Labeling and Packaging", but few manufacturers other than Novo Nordisk responded (see here for Novo Nordisk's letter to the FDA on that topic). Apparently, it was not seen as urgent enough to move ahead with, so nothing was implemented.

While it does sound like it would be easier if every bottle or cartridge of rapid-acting analogs were magenta, whereas every bottle of long-acting analogs were say, red, and maybe blue for "old-style" insulins such as regular or NPH, the Food and Drug Administration apparently sees fast-tracking (see here for more on that) new drugs as more important than reducing errors.

But some mistakes are avoidable if we know what to look for. Now, let's get this on the CDE exam to make sure it is taught to everyone who uses insulin!