Understanding Insulin

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Understanding Insulin

In any discussion of diabetes, the word insulin is almost certain to come up. That’s because a lack of insulin or trouble responding to insulin (a condition called insulin resistance) or both is what is responsible for the high blood glucose levels that characterize diabetes.

Thanks to years of medical research, however, endogenous insulin (that produced by the pancreas) can be replaced or supplemented by exogenous insulin (insulin produced in a laboratory). For people with Type 1 diabetes, injecting insulin (or infusing it with an insulin pump) is necessary for survival: Before the discovery of insulin in 1921, the life expectancy for a person diagnosed with what was then known as juvenile diabetes was less than a year. For some people with Type 2 diabetes, using insulin may be the best — or only — way to keep blood glucose levels in the recommended range, and maintaining blood glucose control is one of the most important things you can do to lower your risk of developing potentially devastating complications.

But even if you never have to take insulin to control your diabetes, it is important to understand what insulin is and what it does in the body. That’s because your lifestyle choices affect the health of your insulin-producing beta cells. Making an effort to lose excess weight, eat healthfully, exercise regularly, and take any prescribed drugs as instructed can prolong the life of your beta cells, so they continue to make the insulin you need.

The role of insulin

Insulin is a hormone that is released by the beta cells of the pancreas, a glandular organ located in the abdomen, in response to a rise in the level of glucose in the blood. Blood glucose levels rise when a person consumes carbohydrate-containing food or drinks, as well as during periods of physical and sometimes mental stress. Insulin prevents a further increase in the blood glucose level and causes it to fall gradually by enabling the glucose to enter the body’s cells, where it is burned for energy or stored as glycogen or fat for later use. While many hormones raise blood glucose levels, only insulin lowers them.

The body needs a small amount of insulin at all times to keep blood glucose levels controlled between meals and overnight. In a person who does not have diabetes (or who does have diabetes but whose pancreas still produces insulin), the pancreas constantly secretes this small amount of so-called background, or basal, insulin. A person whose pancreas does not produce insulin (or does not produce enough) can compensate by injecting an intermediate- or long-acting insulin or by using an insulin pump that is programmed to continuously deliver small pulses of short- or rapid-acting insulin.

At mealtimes, blood glucose levels rise as carbohydrates are broken down to glucose and other simple sugars and enter the bloodstream. A healthy pancreas responds by releasing a burst of insulin in two phases, the first occurring almost as soon as food is eaten and lasting about 15 minutes, and the second occurring more gradually over the next 1 1/2–3 hours. In a person who doesn’t have diabetes, the amount of insulin released matches the rise in blood glucose. In people with Type 2 diabetes, a diminished first-phase insulin response is often the first sign of pancreatic insufficiency.

People who use insulin can match the pancreas’s action by injecting a dose of short- or rapid-acting insulin before the meal or by taking a bolus dose with an insulin pump. Since the goal is to match the premeal insulin dose to the expected rise in blood glucose following the meal, and since the amount of carbohydrate in the meal predicts the rise in blood glucose, the current practice is to match the premeal insulin dose to the amount of carbohydrate in the meal. This requires knowing your insulin-to-carbohydrate ratio — or how much insulin you need to “cover” a certain number of grams of carbohydrate. Your diabetes care team can help you determine your insulin-to-carbohydrate ratio by looking at your food records and your blood glucose monitoring records for before-meal and after-meal blood glucose levels. They will also take your overall insulin requirements into consideration.

Types of diabetes

In Type 1 diabetes, an autoimmune process destroys the insulin-producing beta cells of the pancreas, leaving it unable to make insulin. People with Type 1 diabetes must therefore inject or infuse insulin for survival. While some people appear to have a genetic predisposition to develop Type 1 diabetes, exactly what sets off the autoimmune destruction of the beta cells is unknown.

In Type 2 diabetes, some degree of insulin resistance is typically present. Initially, the pancreas may release more insulin than normal to compensate for the insulin resistance, but eventually, the pancreas is believed to “burn out” from overproduction, and blood glucose levels rise. However, treatments other than insulin therapy are usually tried first for Type 2 diabetes. In most cases, insulin resistance can be improved with moderate weight loss, so treatment recommendations generally include lifestyle adjustments such as changes in diet and increased physical activity. Oral and injectable blood-glucose-lowering medicines are also often used in the treatment of Type 2 diabetes. (These oral and injectable medicines are not insulin.) If dietary changes, increased physical activity, and oral medicines are unable to keep blood glucose levels adequately controlled, insulin therapy may be added to the diabetes treatment regimen or substituted for the oral drugs.

Diabetes and pregnancy

In any pregnancy, the need for insulin dramatically increases around the 16th week of gestation. From then on, more and more insulin is necessary to maintain normal blood glucose levels as the pregnancy progresses.

In women with Type 1 diabetes who are pregnant, careful blood glucose monitoring to adjust insulin doses is necessary over the course of the pregnancy. In women with Type 2 diabetes, insulin is usually the drug of choice to manage blood glucose levels during pregnancy and also requires adjustments, as needed, throughout the pregnancy. Women with Type 2 diabetes who are taking oral blood-glucose-lowering medicines prior to pregnancy are urged to plan their pregnancy and, typically, to begin using insulin prior to conception. While a few studies have examined the use of oral diabetes drugs during pregnancy, many health-care providers feel they do not yet know enough about the effect of these medicines on the fetus to advocate their use at this time.

A temporary type of diabetes that complicates about 7% of all pregnancies among women not diagnosed with either Type 1 or Type 2 diabetes is called gestational diabetes. The high blood glucose levels that occur in gestational diabetes are usually first recognized around the 24th to 28th week of pregnancy. They are due to increased insulin resistance, which is generally caused by the pregnancy hormones as well as the weight gain that normally occurs in pregnancy. About 75% of women with gestational diabetes can maintain normal blood glucose levels by making lifestyle changes, such as following a meal plan and getting regular physical activity. However, if blood glucose levels remain too high, insulin is currently the drug of choice for treatment for gestational diabetes.

Synthetic insulin

Insulin that is used in diabetes treatment is not and never was extracted from human pancreases (although earlier forms of insulin were, in fact, extracted from pig and cow pancreases). Human insulin is manufactured using recombinant DNA technology (often called genetic engineering) in a laboratory; it is identical in structure to what a human pancreas produces. Insulin analogs, which are structurally different from human insulin, are also manufactured in labs using similar processes.

Although genetically engineered human insulin is identical to the natural product, insulin that is injected into the fatty tissue under the skin does not act the same as insulin secreted from the pancreas directly into the bloodstream. Injected insulin reaches the bloodstream more slowly, so there’s a delay in when it starts lowering blood glucose levels. Because these differences make it difficult to control blood glucose levels with injected insulin, much research has gone into altering synthetic insulin so that it behaves more like the insulin that is secreted by a pancreas. The rapid-acting insulin analogs are one of the results of this research.

Insulin is now available in a variety of types that are categorized according to action time. These types include ultra-rapid-acting insulin, rapid-acting insulin, short-acting insulin, intermediate-acting insulin, long-acting insulin, and ultra-long-acting insulin. Insulin can also be purchased in mixtures of intermediate-acting and either rapid-acting or short-acting insulins.

Ultra-rapid-acting insulin. Insulin human inhalation powder (brand name Afrezza) is currently the only ultra-rapid-acting insulin on the market. The medicine is strongest (peaks) within 12 to 15 minutes of administration, with insulin returning to baseline levels after about 180 minutes. This insulin is taken at the beginning of each meal.

Rapid-acting insulin. The rapid-acting insulin analogs currently available include insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra).

Rapid-acting insulin typically starts working in 5 to 15 minutes, peaks in 45 to 90 minutes, and diminishes in activity 3 to 5 hours after injection. Because it starts working so quickly, rapid-acting insulin is generally taken within 15 minutes of eating — either within the 15 minutes before a meal or as much as 15 minutes after starting to eat. Rapid-acting insulin comes close to mimicking the pancreas’s first-phase insulin release in response to food. If timed correctly and accurately matched to the amount of carbohydrate in the meal, a dose of rapid-acting insulin before a meal can help keep blood glucose levels in target range after the meal.

All of the rapid-acting insulin preparations are approved for use in insulin pumps. In the case of pump therapy, rapid-acting insulin is used not just for bolus doses at mealtimes but also as basal insulin around the clock.

Short-acting insulin. Regular, or short-acting, human insulin usually starts working about 30 minutes after injection, is strongest (peaks) 2 to 4 hours after injection, and decreases in activity 5 to 7 hours after injection. People who use Regular insulin are typically advised to take it approximately 30 minutes before eating a meal so that the rise in the level of insulin in the bloodstream matches the rise in blood glucose level.

Intermediate-acting insulin. Intermediate-acting human insulin, or NPH, generally starts working in 1 to 2 hours. It peaks in 6 to 14 hours, and its activity decreases 16 to 24 hours after injection. Intermediate-acting insulin is commonly prescribed once or twice daily, usually before breakfast and/or supper, to enhance overall blood glucose control. In some cases, intermediate-acting insulin may be recommended at bedtime to help control overnight and early morning blood glucose levels. In either situation, the insulin would be providing a basal-type effect.

Long-acting insulin. Long-acting insulins, sometimes called basal insulins, are typically given once daily and include the insulin analogs glargine (Lantus, Toujeo, Basaglar) and detemir (Levemir). Glargine and detemir, which are clear rather than cloudy or milky in appearance, are considered to be “peakless” insulins. Their effects last for up to 24 hours. Glargine and detemir should never be mixed with another type of insulin.

Ultra-long-acting insulin. Insulin degludec (Tresiba) is a once-daily basal insulin analog with a half-life of 25 hours and a duration of action of at least 42 hours.

Premixed insulins. Premixed insulin preparations contain intermediate-acting insulin that is mixed with either rapid- or short-acting insulin in varying percentages. The advantage to using a premixed preparation is that you don’t have to mix the insulins yourself when drawing up an injection or take two injections rather than one.

All of the insulin analogs require a prescription from a physician for purchase. Human insulin does not require a prescription for purchase in some states; however, a prescription is usually necessary for insurance coverage. Use of insulin therapy should always follow a physician’s recommendation and prescription.

Challenges of insulin therapy

Insulin may be a lifesaver for people with Type 1 diabetes and may offer the best chance of achieving optimal blood glucose control for many with Type 2, but it can be a challenge to use. The body’s need for insulin is based on many things — including body weight, stage of growth, food intake, physical activity, use of certain drugs, and physical or mental stress — all of which can change from day to day.

When there is too much insulin in the bloodstream relative to the body’s needs, hypoglycemia, or low blood glucose, results. Hypoglycemia can occur as the result of skipping or delaying a meal, taking more insulin than is necessary to control blood glucose levels, engaging in unusual or more frequent physical activity than normal, and consuming alcohol. People who use insulin should be aware of the signs and symptoms of hypoglycemia, as well as how to treat it. (See “Treating Hypoglycemia.”)

Many people gain weight when they start insulin therapy, usually because their bodies are now absorbing glucose that was previously exiting the body in the urine. For people who had lost a lot of weight because of their diabetes, the weight gain may be welcome, but for many, it is not. To slow any weight gain and maintain a healthy weight, it’s necessary to consume only as many calories as your body needs, given your level of physical activity. A registered dietitian can help you determine what and how much to eat to maintain a healthy weight and optimal blood glucose control. It’s also worth noting that weight loss (through burning more calories than are consumed) can lower insulin needs, while weight gain can increase it.

It’s possible to have an allergic reaction to insulin. Symptoms of a local reaction at the injection site include slight swelling, itching, and redness. Local reactions can occur as the result of preservatives used in the insulin (not the insulin itself), the material used in the needle, products used to cleanse your skin prior to injection, or using an injection technique that injures the skin. Determining the cause is important. Let your diabetes care team know if any of these symptoms occur. Symptoms of a more serious, systemic allergic reaction include shortness of breath or wheezing, fast heart rate, clamminess, and a rash that occurs all over your body. If any of these occur, notify your physician immediately.

Skin changes due to repeated insulin injections, such as slight pitting or areas of thickened skin, are rare but possible. If you notice that your skin is changing in the area you inject insulin, consult your diabetes care team. A change in injection technique or needle size may solve this problem.

When insulin doses are inadequate relative to the body’s needs, high blood glucose results. Common causes of high blood glucose include not taking enough insulin for the amount of food eaten and physical stress such as an illness or infection. Very high blood glucose can lead to serious consequences such as diabetic ketoacidosis or hyperosmolar hyperglycemic state, both of which usually require hospitalization. Chronically elevated blood glucose, even when it doesn’t cause an acute crisis, can damage the blood vessels and nerves in the body over time. Your diabetes care team can help you learn to keep your blood glucose in target range and develop a plan for responding to high blood glucose if it occurs.

Insulin delivery

While alternative delivery methods continue to be researched, currently the only ways to take insulin outside a medical setting in the United States are to inject or infuse it into the fatty tissue just below the skin and to inhale it. There are a few device options for doing this. The body areas used most commonly for insulin injections or to insert an insulin pump infusion set are the abdomen, buttocks, and thighs. (See “Insulin Injection Sites.”)

Insulin vial and syringe. The traditional way of taking insulin, using a syringe to draw insulin from a vial and inject it, is widely used in the United States. Technique is important when administering insulin with a syringe and is best learned with guidance from a health-care provider. Insulin syringes come in a variety of sizes to accommodate larger or smaller doses. Different lengths and gauges of needles are available, too. Your diabetes care team can help determine the right size syringe and needle for you.

Insulin pens and dosing devices. Insulin pens are usually the size of a large fountain pen. Some are reusable, and some are disposable. Reusable insulin pens and devices use cartridges of insulin that are replaced as they are emptied. Disposable pens and devices are prefilled with insulin and discarded when empty. However, there is a limited time an insulin pen or device can be stored at room temperature. Check package inserts for specifics, and discard any cartridge or disposable pen or device that has been kept at room temperature longer than specified by the manufacturer.

The general procedure for injecting insulin with a pen or dosing device is as follows: A disposable pen needle is attached, the dose is dialed in, the needle is inserted into the skin, and a button on the pen is pressed to deliver the insulin. However, because the steps for using a pen are somewhat different from those for using a syringe, and because each device may work a little differently, it’s important to read the manufacturer’s package insert for specific instructions for each pen or dosing device.

Insulin pump. Insulin pumps are small, computerized, mechanical devices about the size of a cell phone. Insulin pumps deliver insulin by pumping rapid- or short-acting insulin, typically through plastic tubing, to a small catheter or needle that is inserted into the fat layer under the skin and taped in place. Pumps are generally programmed to deliver a steady, small dose insulin (basal insulin), and the user delivers larger amounts of insulin (bolus doses) based on the amount of carbohydrate in meals and snacks. To learn more, consultation with a physician and a diabetes educator with expertise in insulin pump therapy is recommended.

Inhalation device. The only insulin inhalation device currently on the market is a whistle-size device into which single-dose cartridges of insulin powder is loaded for inhalation.

Insulin jet injectors. Jet injectors send a fine spray of insulin through the skin using a high-pressure air mechanism instead of a needle. If used incorrectly, injectors can be painful, injure the skin, and result in inaccurate dosing, so education and training on use of the injector device is important.

When insulin is prescribed, it is important that the method of delivery be individualized. Expense and insurance coverage may influence your choice, as may issues such as convenience and level of manual dexterity. Work with your diabetes care team to choose and learn to use the best method for you.

How am I doing?

Blood glucose self-monitoring lets you know how well your treatment is working. Your diabetes care team can help you decide when and how often to monitor and also how to interpret your monitoring results. Most insulin users should check their blood glucose level at least three times daily. Checking both before meals and after meals (one to two hours after eating) can be useful for fine-tuning bolus, or premeal, doses. Checking first thing in the morning, before meals, at bedtime, and in the middle of the night can assist with determining basal insulin needs. Any changes in insulin dosing should be made cautiously and with the direction of your diabetes care team.

Powerful medicine

While no one necessarily enjoys injecting insulin or inserting a pump catheter, for many people with diabetes, insulin is the most effective therapy for maintaining blood glucose control, along with healthy lifestyle behaviors such as meal planning and getting regular physical activity. This is important to remember, because the devastating complications that are associated with diabetes result largely from high blood glucose levels — and can be prevented by keeping blood glucose levels close to the normal range.

If you have questions about your insulin therapy or whether it might be a good time for you to start using insulin, speak to your diabetes care team. The more you understand your diabetes treatment, the more you are able to benefit from it.

Originally Published July 25, 2006

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