What Veterinary Nurses Need to Know About Insulin

Insulin is administered daily in veterinary hospitals across the United States. Because of its frequent usage, the veterinary healthcare team must be comfortable working with it and discussing it with clients. This article reviews the types of insulin, variety of functions insulin performs, considerations before insulin administration, and applications beyond the management of diabetes.

Insulin is a naturally occurring hormone produced in the pancreas. After a meal, carbohydrates are broken down into glucose, which increases the blood glucose level. In response to this increase, the pancreas releases insulin. Insulin lowers blood glucose in 2 ways. One way is insulin binding to cellular receptors that unlock glucose channels within cells so that glucose moves intracellularly via those open channels, decreasing blood glucose levels. Then, intracellular glucose is used to produce adenosine triphosphate (ATP). The second way insulin lowers blood glucose is by interrupting the normal release of glucose from the liver. Glycogen is stored in the liver and can be broken down into glucose via glycogenolysis, thereby providing a patient with quick access to glucose needed for immediate energy or to compensate for blood glucose decreases between meals. When insulin levels are high, the liver suppresses glycogen breakdown and shifts to glycogen storage, thereby stopping glycogen breakdown and glucose release into the bloodstream so that blood glucose levels will not further increase.

In addition to those 2 ways of lowering blood glucose, insulin serves other functions. Insulin stimulates glycogen synthesis. If the liver becomes saturated with glycogen, additional glucose can be absorbed by adipose tissue, where it then aids lipoprotein synthesis. Insulin also manages the breakdown of proteins and lipids. Last, insulin affects some electrolyte and amino acid levels, specifically uptake of potassium and amino acids and excretion of sodium. Because insulin lowers potassium levels, it can be used to treat hyperkalemia.

Diabetes Mellitus

The most common canine and feline endocrine disorder associated with the pancreas is diabetes mellitus.¹ In humans, diabetes mellitus is generally categorized as type 1 or type 2. The forms of canine and feline diabetes mellitus are similar but not identical to those of humans.

Type 1 (insulin-dependent) diabetes mellitus was previously referred to as juvenile diabetes, although it can occur at any age and is characterized by the destruction of β-cells. Type 1 diabetes mellitus is associated with a total deficiency of naturally occurring insulin. Destruction of β-cells results in the inability to produce insulin and, therefore, the inability to regulate spikes in blood glucose. The most frequent type of diabetes mellitus among dogs is similar to type 1, whereas it is considered rare among cats.^1,2

Type 2 (non–insulin-dependent) diabetes mellitus is characterized by insulin resistance and β-cell dysfunction that results in a relative insulin deficiency, which differs from the absolute deficiency of type 1. In humans and veterinary patients, type 2 diabetes mellitus is associated with obesity. Type 2 diabetes mellitus is more common among cats. Obesity-induced insulin resistance can develop in dogs yet does not seem to progress to type 2 diabetes mellitus.³

Given the lack of endogenous insulin in patients with type 1 or 2 diabetes mellitus, exogenous insulin therapy is usually required to return a patient with recently diagnosed diabetes mellitus to a normoglycemic state and to maintain that state.

Types of Insulin

Among the variety of insulin types and brands, each type of insulin has different indications. Insulin is either short- (i.e., rapid), intermediate-, or long-acting (TABLE 1). Many of the insulin products used in veterinary medicine were developed for human use and, as such, are not approved by the FDA for veterinary use; however, off-label use of insulin products is common, and reliable dosing can be achieved. The task force for the 2018 AAHA Diabetes Management Guidelines for Dogs and Cats found a consensus with regard to using veterinary-formulated insulin products as a first choice for both dogs and cats but also reported that other formulations (i.e., not veterinary specific) are generally used and accepted.⁴

Short-acting insulin has a quick onset of action, 30 to 60 minutes, and reaches peak action 2 to 4 hours after administration. With its quick onset of action, short-acting insulin is the insulin of choice for emergency situations. When a patient exhibits clinical signs of hyperglycemia or diabetic ketoacidosis (DKA), short-acting insulin can be given to quickly lower blood glucose levels. If a patient with unregulated diabetes is also hyperglycemic, it can be difficult to know how much insulin will be needed to lower blood glucose and maintain a normal glucose level between insulin doses. Short-acting insulin can be given as often as hourly or in a constant-rate infusion (CRI), which enables practitioners to start with a lower dose and titrate as needed to reach the desired blood glucose level. Otherwise, practitioners would risk lowering blood glucose to a hypoglycemic value and possibly have that value persist for an extended period. Although short-acting insulin is the choice for emergency situations, it is not ideal for maintenance insulin therapy for a patient with diabetes.

Intermediate- and long-acting insulin are indicated for maintenance insulin therapy for a patient with regulated diabetes mellitus. Intermediate-acting insulin has an onset of action of 1.5 to 2 hours and reaches peak action 2 to 11 hours after administration. It can also be used as a bridge back to a long-acting maintenance insulin after a crisis. Long-acting insulin has an onset of action up to 3 hours and reaches peak action 4 to 26 hours after administration.

Insulin Administration

Insulin is given by injection, and route of administration (IM, SC, or IV) depends on the type of insulin. Only regular insulin (a short-acting insulin) should be given intravenously as its use in an emergency suggests. Intramuscular injection of insulin should result in a quicker onset and peak than subcutaneous administration. Insulin should be given subcutaneously only for maintenance therapy. Multiple attempts have been made in human medicine to produce an orally administered insulin but were unsuccessful. Buccal administration has shown slightly more promise than oral and is available in some countries. However, the author could not find evidence of buccal products being available in the United States.⁵

Insulin must be administered with insulin syringes, which are calibrated to the insulin concentration and can vary with the kind of insulin. The most common calibration is a U-100 syringe. The calibration of a U-100 syringe is 100 units per 1 mL (1 U equals 0.01 mL). Because of this convenient conversion, U-100 syringes are also commonly used to administer small doses of other drugs. Similarly, the calibration of a U-40 syringe is 40 units per 1 mL. A conversion can be done to use U-40 syringes for mL dosing, but because the math is not as straightforward it is not often done. Two brands of insulin to note that use U-40 syringes are Vetsulin (Merck, merck-animal-health-usa.com) and ProZinc (Boehringer Ingelheim, bi-animalhealth.com).

When insulin sits undisturbed, it can settle; therefore, mixing the bottle before administration is essential. Generally, insulin bottles should be gently rolled along the hand to mix. Exceptions to this are Vetsulin, which should be shaken until it is “uniformly milky,” and glargine, which does not need to be rolled or mixed.^6,7 Before use, the insulin vial’s rubber stopper should be wiped with alcohol and air-dried to avoid contamination. Unopened vials of insulin should be stored in the refrigerator. Opened bottles are typically refrigerated as well, although some can be left at room temperature. Consult the package insert for specific storage instructions.

Patients in critical condition will likely need serial insulin injections for several hours to days. The 2 options for insulin administration for critical patients are serial injections and CRI. Serial injections result in more peaks and troughs in blood glucose levels, whereas CRIs result in steadier levels. Nonetheless, a CRI limits patient handling and requires vigilant monitoring of fluid rates to minimize the potential for fluid overload. Overall, the method chosen is often based on consideration for the practitioner’s experience and training as well as the patient’s temperament and condition.

Regardless of the administration method, contingency orders are an excellent way to streamline a patient’s treatment needs. Contingency orders enable a veterinary nurse to give the necessary insulin dose or CRI adjustment right away, then notify a veterinarian when they become available. If a patient’s blood glucose level is being checked every 2 hours, a lack of contingency orders can possibly delay treatment (i.e., a veterinary nurse must find a veterinarian after every glucose check to get directions for the injection dose or CRI adjustment). TABLE 2 is a CRI contingency order template. (The veterinarian will base the actual ranges and dosing on the patient.)

Alternatives to Insulin

For decades, insulin has been the standard of care for diabetes mellitus treatment. However, advances in medicine have resulted in noninsulin treatment options. Bexagliflozin oral tablets (Bexacat; Elanco, elanco.com) and velagliflozin oral solution (Senvelgo; Boehringer Ingelheim, bi-animalhealth.com) are both approved for the treatment of diabetes mellitus in cats that have not been treated previously with insulin and do not have DKA.⁸ In addition, these oral medications should not be initiated in patients with comorbidities. Specific contraindications can be found on the website for each drug.^8,9

Bexagliflozin and velagliflozin are classified as sodium–glucose cotransporter 2 (SGLT2) inhibitors. Sodium–glucose transport proteins are found in the nephrons of the kidney and are responsible for reabsorption of glucose in the glomerulus, which returns glucose to circulating blood. SGLT2 inhibitors prevent reabsorption of glucose, thus lowering blood glucose levels. Because of their mechanism of action, risks for hypoglycemic episodes are lower with these medications. Patients may reach steady glucose levels in as short as a week after treatment onset with bexagliflozin and velagliflozin. Of note, these medications were approved by the FDA within the past 2 years. More will be learned about their adverse effects and complications after their use becomes more prolific.

Insulin as Treatment for Hyperkalemia

One of the roles of insulin is managing the cellular uptake of potassium, which is particularly applicable in cases of feline urethral obstruction. A cat with a urethral obstruction, regardless of duration, is often hyperkalemic. After the urethra becomes blocked, pressure increases in the tubules of the kidney, which compromises potassium excretion. As a result, potassium cannot be removed from the blood and the patient’s potassium level begins to increase. The potassium level will continue to rise until the blockage is relieved and urine flow is restored.

In a healthy patient, potassium tends to be inside the cell (i.e., in the intracellular fluid). When blood glucose levels rise, potassium moves out of the cell (i.e., into the extracellular fluid). When insulin is given, sodium–potassium ATPase pumps are stimulated, which decreases the blood glucose level, forcing potassium back into the cell. For a cat with a urethral obstruction, administering a dose of regular insulin at the time of unblocking will cause potassium to move intracellularly as blood glucose decreases, which helps alleviate clinical signs of hyperkalemia as potassium moves out of the extracellular fluid and into the intracellular fluid. In addition, when this treatment is used, the patient should receive a 2.5% to 5% dextrose CRI for several hours. Blood glucose should be monitored serially until normal blood glucose levels are being maintained and it is evident that there are no further effects of insulin on blood glucose level.

Diabetic Ketoacidosis

DKA is generally considered to be a complication of diabetes mellitus, although some evidence indicates that DKA can be incited by other conditions that produce ketones from fatty acids.^10,11 Ketone production occurs when there is not enough, or any, glucose being transported into the cells to produce ATP.

Hyperglycemia is a component of DKA, but it is not the primary focus of treatment for a patient with this complicated disease process. Before insulin administration, fluid therapy should be administered and electrolyte abnormalities should be addressed. Fluid therapy can decrease blood glucose levels; some speculate this results from improved renal perfusion.¹¹ Because of this potential response to fluid therapy, insulin administration at treatment onset can result in hypoglycemia and/or osmotic shifts. Ideally, electrolyte abnormalities should also be corrected before insulin administration. Initially, patients with DKA can be hyperkalemic; however, they can quickly become hypokalemic after initiation of fluid therapy. Because insulin administration is a way to decrease potassium, it is wise to refrain from administering insulin to patients at risk for hypokalemia until potassium levels stabilize.

After several hours of fluid therapy, hyperglycemia should be addressed via insulin therapy. Short-acting insulin is used for DKA treatment. Generally, regular insulin is administered intramuscularly or as a CRI. After hourly intramuscular administration, blood glucose levels should also be measured hourly; after a CRI, every 2 hours.¹²

After a patient’s blood glucose measurement is within normal range and other clinical signs of DKA have abated, the treatment can be transitioned to an intermediate- or long-acting insulin for further management of diabetes mellitus, if indicated. Because these patients received insulin for treatment of DKA, they are not candidates for noninsulin therapies.

Client Education

Insulin administration is often long-term, or even lifelong; thus, clients need to have a clear understanding of the medication and the management of their pet’s condition. When insulin is prescribed, explicit instructions for administration, and possibly a checklist of discussion points, are necessary (BOX 1). Without a clear understanding of dosing, administration, and potential adverse effects and complications, a client is at risk for causing their pet insulin-related problems.

Most clients do not have experience giving injections. Ensuring that a client is comfortable with the idea of injecting insulin, before giving a demonstration of how to inject insulin, is most productive. There may be another family member who is a better candidate to give injections; if so, efforts should be made for that person to view a demonstration to avoid any miscommunications to the final caregiver.

The client who will be injecting insulin should practice before leaving the hospital. The demonstration appointment can potentially be scheduled to coincide with the patient’s next dosing time. If that is not possible, then the client can practice giving an injection by using saline or another suitable type of subcutaneous fluid. Regardless of what is injected, the veterinary professional leading the demonstration can give real-time feedback to help the client feel more comfortable with administration.

If a client is monitoring blood glucose levels at home, contingency orders can be created for them to know how much insulin to give and when to not give insulin. Furthermore, clients are often uncertain as to what they should do when their pet does not eat but is acting normally and when their pet only eats part of a meal. Contingency orders can give a client direction for these situations and prevent them from needing to call the clinic.

Regardless of whether a client will measure their pet’s blood glucose at home, they should be educated about the clinical signs of hypoglycemia (e.g., lethargy, weakness, twitching/shaking/tremors, seizures). It should be emphasized to clients that insulin should not be given when any of these signs are present.

Summary

Because insulin is commonly used in veterinary medicine, it is imperative that the veterinary team understands its various roles and applications. Diabetes mellitus is the most common indication for insulin, yet other conditions can be treated with insulin. Educating clients about insulin type, administration route, and glucose monitoring is essential to ensure that patients receive appropriate, safe treatment with insulin at home.