Insulin

Definition

Insulin is a hormone secreted by specialized cells in the pancreas, a large gland lying behind the stomach. Together, insulin and glucagon, another pancreatic hormone, act to control blood sugar (glucose)

levels in the body. Synthetic (artificial) insulin is used to replace the body's insulin when insulin production is absent or defective.

Description

Glucose is a type of sugar that the cells of the body require for producing energy and promoting growth and repair. The body must break down the glucose it takes in from food, however, and transport it from the bloodstream into the cells. When the levels of glucose in the body rise after food is consumed, insulin—secreted by beta cells within the pancreas' islets of Langerhans cells—is released to stabilize the glucose level. When the levels of glucose fall (such as between meals), the pancreas secretes the hormone, glucagon. Thus, the action of both hormones is necessary to keep fasting blood glucose levels within the normal range of 70 to 100 milligrams of glucose per deciliter (mg/dL) of blood. After eating, a normal blood glucose level should be below 180 mg/dL.

In type 1 diabetes mellitus (diabetes), which often begins in childhood or adolescence, the pancreas either does not produce insulin or the amount produced is insufficient. When blood glucose levels rise above 180 mg/dL—a condition called hyperglycemia results. A person with type 1 diabetes must be injected with insulin under the skin (subcutaneously) every day to give the body the insulin it needs to survive. The insulin must be injected because the digestive enzymes in the gastrointestinal tract would break down any oral medication and render it ineffective.

Type 2 diabetes, which often begins in adulthood, is the most common form of diabetes. In type 2 diabetes, the pancreas either produces an insufficient

amount of insulin or the cells of the body do not respond properly to the insulin (called insulin resistance). Often oral medications are effective in treating this form of diabetes, but when drugs fail to control blood glucose levels, insulin injections may be necessary.

Preparations

Since insulin was first discovered in 1922 by Canadian scientists Frederick Banting and Charles Best, there have been many changes in the research and development of its synthetic preparation. The first insulin preparations were purified from pancreas tissue extracted from animals—either pigs or cattle but contained impurities and produced an allergic reaction in some people.

The manufacturing of beef insulin for human use in the United States was discontinued in 1998, and in 2006, pork insulin for human use was no longer manufactured or marketed in the United States. After 2005, individuals were allowed to import beef or pork insulin for their personal use from a foreign country only under strict US Food and Drug Association (FDA) and US Department of Agriculture (USDA) guidelines.

Since the 1980s, however, most insulin—referred to as “human insulin,” has been made synthetically by recombinant deoxyribonucleic acid (DNA) technology, or genetic engineering. This insulin, which is chemically identical to its human counterpart, is produced in a laboratory. The insulin-encoded gene is cut from a human chromosome and inserted into a rapidly reproducing weakened strain of the common bacterium, Escherichia coli (E. coli), which inhabits the human digestive tract. Thus, the bacterium is the factory that produces the genetically engineered insulin. Yeast cells are also used to manufacture insulin. In this way, large amounts of insulin can be created relatively quickly and cost efficiently. As of 2008, there were over 20 types of insulin products available in the United States obtainable in a variety of delivery systems, including vials, prefilled syringes, cartridges, pumps (computerized devices worn on the belt or in the pocket), jet injectors, and pens.

In 2006, the FDA approved the first inhaled insulin combination product for diabetes treatment. Exubera, a short-acting inhaled powder form of recombinant human insulin for the treatment of adults with type 1 or type 2 diabetes, was the first new insulin delivery option introduced since the discovery of insulin in the 1920s. But in 2007, the drug manufacturer withdrew the product from the market because the drug was found no more effective than the injectable forms of insulin and was more costly. Other drug companies continued their work on an inhaled product.

Duration of action

The terms used to describe the time it takes for different types of insulin to work inside the body are

• Onset, or the amount of time needed for the insulin to begin working
• Peak, or the amount of time needed for the insulin to reach maximum effectiveness
• Duration, or the amount of time that the insulin remains effective

Types of insulin

The four basic types of insulin and their onset, peak, and duration—and examples of each—are as follows:

• Rapid-acting—begins working after 15 minutes, peaks in 30 to 90 minutes, and has a duration of 3 to 4 hours (insulin aspart [Novolog], insulin lispro [Humalog], and insulin glulisine [Apidra])
• Short-acting—begins working in 30 to 60 minutes, peaks in 2 to 3 hours, and has a duration of 3 to 6 hours (regular [R] humulin or novolin)
• Intermediate-acting—begins working in 90 minutes to 6 hours, peaks in 4 to 14 hours, and has a duration of up to 24 hours (Neutral Protamine Hagedorn [NPH]
• Long-acting—begins working in 6 to 14 hours and remains effective for 24 to 36 hours (insulin glargine [Lantus], insulin detemir [Levemir])

Many people with diabetes use combinations of different types of insulin to better control and manage their condition. These mixtures include:

• Humalog Mix 75/25 (75% insulin lispro protamine and 25% insulin lispro)
• NovoLog Mix 70/30 (70% aspart protamine and 30% insulin aspart)
• For patients using human insulin, an alternate mixture is available consisting of 70% NPH and 30% regular insulin

Recommended dosage

The recommended dosage and frequency of insulin injection varies with the individual and depends on the type of diabetes diagnosed (type 1 or type 2), the type and brand of insulin prescribed, as well as a variety of additional factors, such as

• age
• allergies or sensitivities to medications
• concurrent medical conditions
• condition of injection sites
• daily routines
• duration and phase of diabetes
• eating habits
• exercise regimen
• lifestyle habits such as drinking or smoking
• results of blood glucose monitoring
• weight

Precautions

It is important for individuals on insulin therapy to follow their physician's instructions regarding diet, exercise , and lifestyle and to take insulin exactly as prescribed. Also, the type of insulin or the brand or model of syringe or needle should not be switched without consulting the prescribing physician. Because an individual's insulin needs may change over time—for example, older adults often adapt to higher blood glucose levels than younger people—dosages may require periodic adjustment.

Other issues to keep in mind when using insulin are listed below.

• Be sure that the insulin is exactly the kind and dosage the doctor ordered and that its expiration date has not passed.
• Do not use a vial that contains visible lumps in the insulin.
• Clean the site of the injection thoroughly with an antiseptic, such as rubbing alcohol, before injecting the insulin.
• Change the injection site daily.
• If a physician prescribes two types of insulin for better glucose control and recommends mixing the insulin into one syringe, always draw the regular insulin (clear) into the syringe first. Also, do not shake the bottle; tip it gently from side to side to mix.
• Some insulin mixtures take time to combine; others react quickly and require immediate injection, so consult a doctor or pharmacist before using any mixtures.
• When traveling, always carry an abundant supply of diabetic medications and supplies and, if possible, a prescription for insulin and syringes.
• Do not store insulin in a place that is extremely hot, like a the glove compartment of a car, or extremely cold, like a freezer.
• Check with a doctor or pharmacist before taking any over-the-counter medications, such as those for cough, cold, diet, allergy, asthma, or sinus conditions. These products may affect blood glucose levels.
• Insulin requirements may change in the presence of other illnesses, so consult a doctor when other conditions are diagnosed.
• Blood glucose levels should be monitored in both mother and child during pregnancy and while the mother is nursing.

Side effects

Like all prescription medications, there are some side effects to keep in mind when using insulin. Minor side effects include skin reactions such as redness, swelling, itching , or rash near the injection site. To avoid this reaction, it is important to change injection sites with each shot. Serious side effects are often related to allergic reactions (severe skin rash) or hypoglycemia.

Hypoglycemia

Hypoglycemia (low blood glucose) is the most common side effect that occurs when taking insulin, especially when too much insulin is taken. A severe insulin overdose may cause disorientation and coma , and immediate medical attention is required. Symptoms of hypoglycemia include

• blurred vision
• confusion
• drowsiness
• depression
• feeling cold
• feadache or lightheadedness
• feart palpitations
• irritability
• muscle weakness
• nausea
• sleep problems
• sweating
• tingling in the lips, hands, or feet
• tremors

If symptoms are mild, eating something or drinking a beverage that is high in sugar (for example, fruit juice) often improves hypoglycemia. Discussing the reaction with a physician to determine the source of the problem is advised.

Hyperglycemia

Too little insulin may cause symptoms of hyperglycemia (high blood glucose), including

• appetite loss
• confusion
• dry skin
• fatigue
• flushing
• frequent urination
• fruity breath odor
• rapid breathing

A doctor may modify the dosing schedule or change the insulin dosage if these symptoms occur.

Interactions

A wide variety of medications, foods, and supplements interact with insulin.

Increased insulin action

Some medications are known to increase the action of insulin and may lower blood glucose to a dangerous level. To prevent hypoglycemia when using these drugs, the insulin dosage may need to be reduced. Such drugs or substances include

• alcohol
• monoamine oxidase (MAO) inhibitors (phenelzine [Nardil])
• beta blockers (propranolol [Inderal])
• salicylates (aspirin or salsalate [Disalcid])
• anabolic steroids (methyltestosterone [Android])

Although other drugs may increase the blood glucose-lowering effect of insulin, they are less likely to interact with insulin or have less of an effect. Such drugs include

• tetracycline antibiotics (doxycycline [Vibramycin] or guanethidine [Ismelin])
• oral hypoglycemic drugs (glyburide [Diabeta])
• sulfa antibiotics (sulfadiazine)
• angiotensin-convering enzyme (ACE) inhibitors (captopril [Capoten])

In addition, alcohol may increase the action of insulin, leading to hypoglycemia, so people using insulin should avoid alcohol.

Decreased insulin action

Some drugs decrease the effect of insulin. Although interactions between these drugs and insulin are less likely or less serious than drugs that increase insulin action, these drugs include

• calcium channel blockers (diltiazem)
• corticosteroids (prednisone)
• epinephrine
• estrogens
• isoniazid
• niacin
• oral contraceptives
• thiazide diuretics (water pills) such as hydrochlorothiazide or furosemide
• thyroid medications like levothyroxine (Synthroid)

Smoking may also decrease insulin activity and increase the health problems associated with diabetes, so people with diabetes are cautioned to avoid smoking.

Dietary supplements and foods

Any food or dietary supplement—such as garlic , ginger, ginseng, hawthorn, licorice, fenugreek, or nettle—that affects blood glucose levels may alter the amount of insulin required by an individual with diabetes. Although chromium, biotin, vitamin E , or an herb called gymnema sylvestre may boost the body's ability to use glucose, these supplements may increase the risk of abnormally low blood glucose levels when taken in conjunction with insulin therapy. The hormone dehydroepiandrosterone (DHEA ) may also alter sensitivity to insulin. So it is important for a person with diabetes to consult a physician before taking any supplements—or before planning a diet.

Caregiver concerns

Care givers should be sure that, if possible, the person with diabetes

QUESTIONS TO ASK YOUR PHARMACIST

• Will any of my prescription medications, over-the-counter drugs, or supplements interact with insulin?
• What should I do if I miss a dose or have to take it later than the scheduled time?
• Where is the best place to give myself the shot?
• Will you always give me the same brand of insulin?
• Where should I store my insulin?
• How can I tell if I'm having an allergic reaction to insulin?
• Can I smoke or drink while taking insulin?

• Monitors their blood glucose levels throughout the day.
• Stores unopened insulin in a refrigerator between 36 and 46°F and never puts insulin in a freezer. Opened insulin vials may be kept at room temperature for up to a month.
• Injects insulin at the same times each day in relation to meals.
• Draws up their insulin carefully to ensure the correct dosage.
• Does not change insulin dosage, brand, or method of delivery without consulting a physician.
• Writes down the exact time and amount of every insulin shot.
• Learns how to balance food, insulin, and exercise, using information from their physician.
• Rotates the area of the body where shots are given—within an area (arm, leg, buttock), move to a different site for each shot. Each shot should be at least a thumb-width away from the last one given.
• Makes sure that friends and family are aware of the symptoms of an insulin reaction and know what to do if they observe any of the symptoms in the person with diabetes.
• Carries a card or wears a bracelet that identifies the person as a diabetic.
• Always has insulin and syringes handy.
• Eats on a regular schedule and avoids skipping meals.

KEY TERMS

Diabetes mellitus —Also known as “diabetes,” a group of metabolic diseases characterized by high blood sugar (glucose) levels, which result from defects in the production or action of insulin, or both.

Glucagon —A hormone produced by the pancreas that raises blood sugar levels and has the opposite action of insulin.

Glucose —Also known as dextrose, the main sugar the body makes from proteins, fats, and carbohydrates. Glucose is carried through the bloodstream to provide energy to all cells in the body with the help of insulin.

Hormone —A chemical substance produced in the body that controls and regulates the activity of certain cells or organs.

Hypoglycemia —Low blood sugar (glucose).

Islets of Langerhans —Pancreatic cell clusters that make and secrete hormones such as insulin.

Metabolism —The biochemical processes that occur within any living organism and involve the buildup and breakdown of substances such as food, and the transformation of these substances into energy.

Pancreas —Organ lying across the back of the abdomen and behind the stomach that contains specialized cells that secrete digestive enzymes and the hormones glucagon and insulin.

Resources

BOOKS

Scheiner, Gary. Think Like a Pancreas: A Practical Guide to Managing Diabetes With Insulin. Emeryville, CA: Marlowe & Company, 2004.

Walsh, John, and Ruth Roberts, Chandra B. Varma, and Timothy Bailey. Using Insulin. San Diego: Torrey Pines Press, 2003.

PERIODICALS

Allen, Scott. “Insulin in the brain: Researchers suspect that low levels might be linked to Alzheimer&s, schizophrenia.” The Boston Globe(January 30, 2006). Available at: http://www.boston.com/news/globe/health_science/articles/2006/01/30/insulin_in_the_brain (March 29, 2008).

Barry, Patrick. “New Route to Insulin-Making Cells.”Science News 173 (February 2, 2008): 78.

Schaffer, Amanda. “In Diabetes, a Complex of Causes.” New York Times(October 16, 2007). Available online at http://www.nytimes.com/2007/10/16/health/16diab.html?_r=1&oref=slogin March 15, 2008.

OTHER

von Wartburg, Linda. “Interesting Insulin Facts.” Diabetes Health. December 20, 2007. http://www.diabeteshealth.com/read/2007/12/20/5572.html(March 29, 2008).

“What Is Insulin?” http://www.endocrineweb.com/diabetes/2insulin.html (March 30, 2008).

ORGANIZATIONS

American Diabetes Association, 1701 North Beauregard St., Alexandria, VA, 22311, (800) 342-2383, http://www.diabetes.org.

BD, 1 Becton Drive, Franklin Lakes, NJ, 07417-1880, (201) 847-6800, (888) 232-2737, (201) 847-4856, http://www.bddiabetes.com.

International Diabetes Federation (IDF), Avenue Emile De Mot 19, Brussels, Belgium, B-1000, +32-2-5385511 l, +32-2-5385114, [email protected], http://www.idf.org.

Genevieve Slomski Ph.D.