Beta Cell Secretion of Insulin

The beta cells in the pancreas secrete approximately 0.2 to 0.5 units/kg/day. A patient weighing 70 kg (154 pounds) secretes 14 to 35 units of insulin per day. More insulin secretion may occur if the person consumes a greater caloric intake. A patient with diabetes mellitus may require 0.2 to 1 units/kg/day. The higher range may be because of obesity, stress, or tissue insulin resistance.

Commercially Prepared Insulin

Insulins are all currently manufactured by using deoxyribonucleic acid (DNA) technology. Human insulin (Humulin) was introduced in 1983 and duplicates insulin produced by the pancreas of the human body. Examples of human insulin include Humulin R and Novolin N. The use of Humulin insulin has a low incidence of allergic effects and insulin resistance. Human insulin analogues are modifications of human insulin with alterations in onset and duration of action. Insulin lispro (Humalog) and insulin aspart (Novolog) are examples of human insulin analogues.

Insulins are usually administered subcutaneously (subQ). Abdominal injections of insulin are absorbed faster than other body sites and found to be more consistent. Newly diagnosed patients with insulin-dependent diabetes are usually prescribed human insulin. In addition, patients in whom hyperglycemia develops during pregnancy or who already have diabetes and become pregnant are usually prescribed human insulin.

The concentration of insulin is 100 units/mL or 500 units/mL (U100/mL or U500/mL, respectively), and the insulin is packaged in a 10-mL vial. Insulin 500 units is only available in short-acting regular insulin (Humulin R and Novolin R). Insulin 500 units is seldom used except in emergencies and for patients with serious insulin resistance (>200 units/day). Insulin 40 units is no longer used in the United States, although it is still used in other countries. Insulin syringes are typically marked in units of 100 units per 1 mL or 50 units per 0.5 mL for insulin U100. Insulin syringes must be used for accurate dosing. To prevent dosage errors, the nurse must be certain that there is a match of the insulin concentration with the calibration of units on the insulin syringe. Before use, the patient or nurse must roll, not shake, cloudy insulin bottles to ensure that the insulin and its ingredients are well mixed. Shaking a bottle of insulin can cause bubbles and an inaccurate dose. Insulin requirements vary; usually less insulin is needed with increased exercise, and more insulin is needed with infections and high fever.

Administration of Insulin

Insulin is a protein and cannot be administered orally because gastrointestinal (GI) secretions destroy the insulin structure. It is administered subQ, at a 45- to 90-degree angle. The 90-degree angle is made by raising the skin and fatty tissue; the insulin is injected into the pocket between the fat and the muscle. In a thin person with little fatty tissue, the 45- to 60-degree angle is used. Regular insulin is the only type that can be administered IV.

The site and depth of insulin injection affect absorption. Insulin absorption is greater when given in the abdominal areas than when given in the thigh and buttock areas. Heat and massage could increase subQ absorption. Cooling the subQ area can decrease absorption.

Illness and stress increase the need for insulin. Insulin doses should not be withheld during illness, including infections and stress. Hyperglycemia and ketoacidosis may result from insufficient insulin.

Types of Insulin

There are several standard types of insulin: rapid acting, short acting, intermediate acting, long acting, and com­binations. Rapid- and short-acting insulins are in a clear solution without any added substance to prolong insulin action. Intermediate-acting insulins are cloudy and may contain protamine, a protein that prolongs the action of insulin, or zinc, which also slows the onset of action and prolongs the duration of activity.

Rapid-acting insulins include insulin lispro (human analog) (Humalog) and human insulin aspart (rDNA origin) (NovoLog). Insulin lispro is formed by reversing two amino acids in human regular insulin (Humulin). Insulin aspart (rDNA origin) is another human insulin analogue in which a single amino acid (proline) has been substituted with aspartic acid to help prevent the molecules from clumping together to allow quicker entry into blood circulation. Insulin lispro and insulin aspart act faster than regular insulin, so they must not be administered more than 5 minutes before mealtime (food should be present before administering these insulins). Patients who are insulin-dependent and take rapid-acting insulin usually require intermediate-acting insulin as well.

Short-acting insulin has an onset of action in 30 minutes to 1 hour. The peak action occurs in 2.5 to 5 hours, and the duration of action is 6 to 8 hours. Regular (unmodified, crystalline) insulin is short-acting insulin that can be administered IV and subQ. Regular insulin is generally given 30 minutes before meals.

Intermediate-acting insulins include neutral-protamine-Hagedorn (NPH), Lente, and Humulin N. Isophane insulins like NPH and Humulin N contain protamine, a protein that prolongs the action of insulin. Humulin L insulin contains zinc, which also prolongs the insulin action time. The onset of intermediate-acting insulin is 1 to 2 hours, peak action occurs in 6 to 12 hours, and the duration of action is 18 to 24 hours.

Insulin glargine (Lantus) is long-acting insulin with an onset of 1 hour. It is evenly distributed over a 24-hour duration of action; thus it is administered once a day, usually at bedtime. Incidence of nocturnal hypoglycemia is not as common as with other insulins because of its continuous sustained release. Insulin detmir (Levemir) is another long-acting insulin that peaks in 6 to 8 hours and lasts for 12 to 24 hours. These two insulins are analogues of human insulin. Approved by the FDA in 2000, Glargine was the first long-acting recombinant DNA (rDNA origin) human insulin for patients with types 1 and 2 diabetes. Glargine and detmir are available in a prefilled 3-mL cartridge for the “OptiPen One” insulin pen device. Some patients complain of more pain at the injection site with the administration of glargine than with NPH insulin.

Combination insulins are commercially premixed. These include Humulin 70/30, Novolin 70/30, Humulin 50/50, and Humalog Mix 75/25. These combinations are widely used. The Humulin 70/30 vials or prefilled disposable pens contain 70% of human insulin isophane (intermediate-acting insulin, NPH) and 30% regular (fast-acting) insulin. The exterior of an insulin pen resembles a fountain pen. The Humulin 50/50 vial or pen contains 50% isophane (NPH) insulin and 50% regular insulin. The Humalog 75/25 mix is available in vials or prefilled disposable pens and contains 75% lispro protamine insulin and 25% lispro “rapid” insulin. Humalog 75/25 helps prevent hypoglycemia, which could occur with the 70/30 or 50/50 combination insulins, and helps control hyperglycemia more effectively. The 75/25 pen contains 300 units of insulin and does not require refrigeration after first use. It can be stored at room temperature for up to 10 days. With these combinations of insulin, the patient does not have to mix regular and NPH insulins as long as one of these combinations is effective. However, some patients need less than 25% or 30% regular insulin and more intermediate-acting insulin. These patients needs to mix the two insulins in the prescribed proportions.

Regular insulin can be mixed with protamine or zinc insulin in the same syringe. However, mixing insulin can alter the absorption rate.

Insulin Resistance

Antibodies develop over time in persons taking animal insulin. This can slow the onset of insulin action and extend its duration of action. Antibody development can cause insulin resistance and insulin allergy. Obesity can also be a causative factor for insulin resistance. Skin tests with different insulin preparations may be performed to determine whether there is an allergic effect. Human and regular insulins produce fewer allergens.

Storage of Insulin

Unopened insulin vials are refrigerated until needed. Once an insulin vial has been opened, it may be kept (1) at room temperature for 1 month or (2) in the refrigerator for 3 months. Insulin is less irritating to the tissues when injected at room temperature. Insulin vials should not be put in the freezer. In addition, insulin vials should not be placed in direct sunlight or in a high-temperature area. Prefilled syringes should be stored in the refrigerator and should be used within 1 to 2 weeks. Opened insulin vials lose their strength after approximately 3 months.

Pharmacokinetics

All insulins can be administered subQ, but only regular insulin can be given IV. The half-life varies. Insulin is metabolized by the liver and muscle and is excreted in the urine.

Pharmacodynamics

Insulin lowers blood sugar by promoting the use of glucose by the body’s cells. Insulin is also active in the storage of glucose as glycogen in muscles. The onset of action of rapid-acting insulin given subQ is 5 to 15 minutes. The onset of action of regular insulin is 30 minutes to 1 hour given subQ and 10 to 30 minutes given IV. The onset of action of intermediate-acting insulin is 1 to 2 hours. The peak action of insulins is important because of the possibility of hypoglycemic reaction (insulin shock) occurring during that time. The peak action for rapid-acting insulin is 30 minutes to 3 hours. The peak time for regular insulin is 2.5 to 5 hours; for intermediate-acting insulin, it is 6 to 12 hours. The nurse needs to assess for signs and symptoms of hypoglycemic reaction, such as nervousness, tremors, confusion, sweating, and increased pulse rate. Orange juice, sugar-sweetened beverages, or hard candy should be kept available and given if a reaction occurs. If patient is unable to ingest fast acting carbohydrates, glucagon may be given. Glucagon promotes the breakdown of glycogen in the liver, raising blood glucose within 10 minutes.

Regular insulin can be given several times a day, especially during the regulation of insulin dosage. Intermediate- and long-acting insulins are usually administered once a day. Regular insulin can be mixed with intermediate-acting insulin (Humulin N), especially if rapid onset of action is needed. When switching from one type of insulin to another, the patient may require a dose adjustment because human insulin has a shorter duration of action.

Sliding-Scale Insulin Coverage

Insulin may be administered in adjusted doses that depend on individual blood glucose test results. When the diabetic patient has extreme variances in insulin requirements (e.g., stress from hospitalization, surgery, illness, or infection), adjusted dosing or sliding-scale insulin coverage provides a more constant blood glucose level. Blood glucose testing is performed several times a day at specified intervals (usually before meals). A preset scale usually involves directions for the administration of rapid- or short-acting insulin.