Pets with Diabetes: Insulin Basics and Syringe facts

Insulin Basics: what is insulin
Insulin is a protein produced by the pancreas, a small organ located in the abdomen. Insulin is made by the pancreatic islet cells (also called the beta cells), then secreted into the blood where it travels throughout the body and helps regulate blood sugar. Insulin is also called a hormone because it is produced in one location (the pancreas) and travels to other cells and regulates their function. Insulin plays a key role in the body's ability to use and store glucose.

There's often a discussion about the differences between cat, dog, human, cow, and pig insulins. Above, you read that insulin is a protein. This protein consists of building blocks called amino acids. There are two chains of amino acids; the A chain and the B chain which are linked together in two locations. Think of two strands of pearls hooked together in two spots. The amino acid sequence of the two chains of bovine (cow) insulin and their cross-linkages can be seen in this image, along with the differences (or similarities) in the amino acid sequences between various species. These amino acid differences give each species' insulin a slightly different structure and activity because the whole insulin protein folds around on itself and has very specific locations where it interacts with the insulin receptor on the cell (remember the lock and key mechanism). Because of this very specific structure-activity relationship, a substitution of one amino acid in a critical location may make the protein deform or not work as well in another species.

Think of a string of pearls that you can twist up into a ball. If you use all one size of tiny pearls, the twisted up string of pearls will take on one shape. But if you substitute one or more medium or large pearls in the string and then try to twist it up, it will take on a different shape.

Types of insulin
The type of insulin refers to the species and formulation. As discussed above, each species has different properties, and combined with different ways of formulating the insulin, the insulins can have a different effect on your pet.

Species

human recombinant (Humulin by Eli Lilly; Novolin by Novo Nordisk)
beef (bovine)
pork (porcine)
combination beef/pork

Formulation

The different formulations of insulin are designed to have different rates of absorption. Some insulins are designed to be absorbed very quickly and others are designed to be absorbed very slowly.

Insulin Type		Brand Name Examples
Rapid-acting	Lispro and Aspart	Humalog, NovoLog
Short-acting	Regular - R	Humulin R, Novolin R.
Intermediate-acting	NPH and Lente	Humulin N, Novolin N, Humulin L
Intermediate-acting	PZI	Blue Ridge PZI (veterinary use only)
Long-acting	Ultralente	Humulin U
Ultra long-acting	Glarine	Lantus
Mixed insulins	70/30 intermediate / rapid	NovoLog Mix
	70/30 intermediate / short-acting	Humulin 70/30, Novolin 70/30
	50/50 intermediate / short	Humulin 50/50

Many pets do very well on human recombinant insulin which is produced in a laboratory by either bacteria (Humulin) or yeast (Novolin) and is identical to human insulin. Due to the minor changes in insulin structure, human recombinant insulin does not work well for some pets. In those cases, other species of insulin can be used. Dogs typically are put on a pork insulin and cats are given beef or combination beef/pork insulin. The choice of species and formulation of insulin will be made by your vet, depending on your pet's response to a particular insulin.

Absorption, Onset, Peak, and Duration
Many people don't understand what happens after the insulin is injected. Here's an explanation of the process.

When insulin is injected subcutaneously, it takes some time for it to be absorbed from the space under the skin into the blood stream and start having an effect. The insulin that is absorbed into the blood and delivered to the cells can bind (connect to) an insulin receptor on the cell. It's like a lock and key for a door. Insulin is the key, and the cell has a receptor (keyhole) that the insulin fits in. Glucose is waiting outside the cell trying to get in. Once the insulin fits into the receptor, the door is unlocked, and the glucose moves from the blood stream into the cell. The amount it takes for the insulin to be absorbed and start lowering the blood glucose is the ONSET time. For some time the total insulin activity will increase and cause the blood glucose (bg) to decrease. As more of the insulin is absorbed and starts to be effective, the total insulin activity gets higher. At some time the insulin will be at its highest activity. This is the PEAK activity time. The bg will be at its lowest (the nadir) as the insulin activity peaks. As the insulin is metabolized (used up) by the body, the total insulin activity decreases. During this time, the BG starts to increase again because there is less insulin working in the body. The total amount of time that the insulin is active is called the DURATION. Some people consider the amount of time that the insulin keeps the bg in an acceptable range to be the duration. The pattern of onset, peak, and duration is sometimes called the activity profile. View sample bg charts showing the relationship between insulin and bg.

The rate of absorption (how fast) and the efficiency of absorption (how much) will effect the onset, peak, and duration of insulin activity. If an insulin is absorbed quickly and completely, you will have a very rapid onset and a sharp peak, and possibly a shorter duration. If an insulin is absorbed slowly, you have a later onset, a smoother shorter peak, and possibly a longer duration.

Not only is each insulin different, but the onset, peak and duration times will be different for individual animals. There are many different types of insulin available and if your pet is not responding well to one insulin, there are many others to choose from. It may take a few tries before you find the one that is best for your pet.

Often, you use an insulin that has about a 12 hour duration. This way you can give 2 shots a day and not have the activity from the first dose overlap the activity of the second dose. During each of these 12 hour cycles, the insulin will have an onset, peak, and duration. All these times depend on your pet and on the type of insulin you are using. With some pets, the insulin duration is close to 24 hours, so only one shot is given each day.

The rates and efficiency of absorption also vary depending on what type of tissue you inject into. We inject our pets subcutaneously - under the skin and into the fatty layer that lies beneath the dermis and above the muscle. One problem with this type of injection is that there is variable absorption depending on many factors (dehydration, blood flow, activity). If you accidentally inject into a vein [intravenous], muscle [intramuscular], skin [intradermal], or if your pet is obese and you inject into a large fat layer, the absorption would be different. It is unlikely that you would inject directly into a vein, but the absorption would then be very fast. Injection into a muscle would result in more rapid absorption compared to a subcutaneous injection. Injecting into a thick fat layer or into the upper layers of the skin (the dermis) would result in slower absorption.

A familiar example
If you are having a hard time understanding these concepts, maybe it will help if you to think of something more familiar like taking an aspirin for a headache. After you ingest the aspirin, it takes a while for the aspirin to get into your blood and start working (onset). After an hour or so, your head feels wonderful and the headache is gone (peak). The aspirin will work well for a few hours (duration) and then it starts to wear off and your headache is back. If aspirin lasts you for 24 hours, then you might need only one aspirin a day to keep the headache away. But if the aspirin lasts for only 12 hours, then you might have to take one in the morning and one in the evening to be headache free.

Chart for onset, peak, and duration times for pets
Note: the times you see in most charts for onset, peak, and duration on the internet are for HUMANS, not for pets. The following table for CATS AND DOGS was adapted from The Pocket Companion to the Fourth Edition of Textbook of Veterinary Internal Medicine. Edited by Stephen J. Ettinger. 1995.

Time (in hours) for beef/pork insulin preparations in dogs and cats.
These are averages and the effect of an insulin in your pet may be different.
Insulin Type (given subcutaneously)	Onset	Time of Maximum (peak) Effect		Duration
Insulin Type (given subcutaneously)	dog or cat	dog	cat	dog	cat
Regular	<0.5	1-5	1-5	4-10	4-10
NPH	0.5-3	2-10	2-8	6-24	4-12
Lente	<1	2-10	2-8	8-24	6-14
PZI	1-4	4-14	3-12	6-28	6-24
Ultralente	2-8	4-16	4-16	8-28	8-24

The authors note that purified pork and recombinant human insulin tend to be more potent (lower the bg farther), act faster (quicker onset and peak), and have a shorter duration that beef/pork insulins.

Insulin Information Web Resources
The package insert that comes with your insulin is the best source of information for handling, storage, and problems with your insulin.

Insulin Info. from the University of Massachusetts Worcester Handbook on Healing. This is an excellent resource for just about all information about insulin: what it is, why it is used, purchasing, storing, mixing, and more.

Syringes

There are four different "properties" of a syringe: U-Number, volume, needle length, and needle diameter.

U-Number: tells you the concentration of insulin that the syringe is calibrated for. The marks on the syringe deliver that many units of the corresponding concentration of insulin. In the U.S. most insulins are U-100 and most syringes are U-100. Each mark on a U-100 syringe corresponds to giving 1 unit of U-100 insulin. A U-40 syringe measures the same way with a U-40 insulin. The only time you need to do some math is if the U of the syringe does not match the U of the insulin (e.g. using a U-100 syringe with a U-40 insulin, or using a diluted insulin).

Assuming you are using a U-100 syringe and U-100 insulin following are true:
Volume: a 3/10cc syringe will deliver between 0 and 30 units of U-100 insulin A 1/2cc syringe can deliver 0-50 units of U-100 insulin. Using the smallest volume syringe you can will help in making the doses more accurate.

Needle length: commonly 1/2 inch, some needles are shorter.

Needle diameter: is measured in gauge. The larger the gauge, the skinnier the needle. So a 29 gauge needle is skinnier than a 27 gauge needle.

References
Insulin structure information from Lehninger: Principles of Biochemistry. Albert L. Lehninger, Editor. Worth publishers, Inc. 1982