Your activity: 6 p.v.

Patient education: Type 1 diabetes: Insulin treatment (Beyond the Basics)

Patient education: Type 1 diabetes: Insulin treatment (Beyond the Basics)
Author:
Ruth S Weinstock, MD, PhD
Section Editor:
David M Nathan, MD
Deputy Editor:
Jean E Mulder, MD
Literature review current through: Feb 2022. | This topic last updated: Aug 18, 2020.

INTRODUCTION — Type 1 diabetes mellitus is a chronic medical condition that occurs when the pancreas, an organ in the abdomen, produces very little or no insulin (figure 1). Insulin is a hormone that helps the body to use glucose for energy. Glucose is a sugar that comes, in large part, from foods we eat. Insulin allows glucose to enter cells in the body where it is needed and stores excess glucose for later use. It has other important actions as well. Without insulin, blood glucose (sugar) levels become too high, and over time, this will harm the body.

Diabetes mellitus is a lifelong condition that can be controlled with lifestyle adjustments and medical treatments. Insulin treatment is one component of a treatment plan for people with type 1 diabetes. Insulin treatment replaces or supplements the body's own insulin with the goal of achieving normal or near-normal blood sugar levels and preventing or minimizing complications.

Many different types of insulin treatment can successfully control blood sugar levels; the best option depends upon a variety of individual factors. With a little extra planning, people with diabetes who take insulin can lead a full life and keep their blood sugar under control.

Other topics that discuss type 1 diabetes are also available. (See "Patient education: Type 1 diabetes: Overview (Beyond the Basics)" and "Patient education: Blood glucose monitoring in diabetes (Beyond the Basics)" and "Patient education: Type 1 diabetes and diet (Beyond the Basics)" and "Patient education: Hypoglycemia (low blood glucose) in people with diabetes (Beyond the Basics)" and "Patient education: Care during pregnancy for women with type 1 or 2 diabetes (Beyond the Basics)".)

DIABETES CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Especially at the beginning of the pandemic, and while the virus was spreading quickly in a lot of places, people in many areas were told to stay home as much as possible in order to slow the spread. This has been particularly important for people with certain underlying health conditions, including diabetes, as they are at increased risk of severe illness if they get COVID-19. COVID-19 infection can also lead to severe complications of diabetes, including diabetic ketoacidosis (DKA). (See 'Infections' below.)

If you live in an area where there are still a lot of cases of COVID-19, your health care provider can talk to you about whether you should make any changes to your usual schedule for getting medical care. In some cases, it may be an option to reduce the number of appointments you need to attend in person. This will depend on several different things, including where you live, how much the virus is still spreading in your community, how well your blood sugar is controlled, what medications you take, and your overall health.

STARTING INSULIN — The pancreas produces very little or no insulin at all in people with type 1 diabetes. For this reason, everyone with type 1 diabetes will require insulin. Insulin is given under the skin, either as a shot or continuously with an insulin pump.

Dosing — When you are first starting insulin, it will take some time to find the right dose. A doctor or nurse will help to adjust your dose over time. You will be instructed to check your blood sugar level several times per day.

Insulin needs often change over your lifetime. Changes in weight, diet (what you eat), health status (including pregnancy), activity level, and work can affect the amount of insulin needed to control your blood sugar.

Most people adjust their own insulin doses, although you will need help from time to time. Meetings with a member of your diabetes care team will usually be scheduled every three to four months; you will review your blood sugar levels and insulin doses at these visits, helping to fine-tune your diabetes control. (See "Patient education: Care during pregnancy for women with type 1 or 2 diabetes (Beyond the Basics)".)

Types — There are several types of insulin. These types are classified according to how quickly the insulin begins to work and how long it remains active:

Rapid acting, eg:

Insulin lispro (sample brand names: Admelog, Humalog, Lyumjev)

Insulin aspart (brand names: Fiasp, NovoLog)

Insulin glulisine (brand name: Apidra)

Short acting, eg, insulin regular (brand name: Humulin R)

Intermediate acting, eg:

Insulin NPH (brand name: Humulin N)

Insulin lispro protamine (mixed with rapid acting insulin lispro [brand name: Humalog Mix])

Long acting, eg:

Insulin glargine (brand name: Basaglar, Lantus)

Insulin detemir (brand name: Levemir; intermediate to long acting; may be needed twice daily)

Very long acting, eg:

Insulin degludec (brand name: Tresiba)

Insulin glargine 300 units/mL (brand name: Toujeo)

Most insulins are supplied in a concentration of 100 units per milliliter. There are also more concentrated forms of insulin that can be used to control high blood sugar (hyperglycemia). The more concentrated forms allow for delivery of the same number of units but in a smaller volume.

Insulin types are used in various combinations to achieve around-the-clock blood sugar control in type 1 diabetes.

INSULIN REGIMENS — Intensive insulin treatment plans are designed to imitate how the nondiabetic pancreas works. Intensive insulin therapy is recommended for most people with type 1 diabetes, although simpler insulin treatments may still be recommended for some people.

Intensive insulin treatment — Intensive insulin treatment is best for keeping blood sugar in near-normal or "tight" control. You will need to take three or more insulin shots per day or use an insulin pump, and you will need to check your blood sugar frequently. Your personal blood sugar goals will be determined by your treatment team to make sure that you are achieving blood sugar levels that are as close to the nondiabetic range as safely possible, while minimizing hypoglycemia (low blood sugar) events. Your insulin treatment regimen will need to be realistic, taking into account your work or school schedules, eating times and preferences, exercise schedule, and cost concerns.

Intensive insulin therapy is recommended for most people with type 1 diabetes, starting as soon as possible after diagnosis. However, this regimen will be successful only if you are fully committed to it and you have a good understanding of the regimen. The different intensive treatment regimens all provide some insulin as a base or "basal" supply, which is meant to provide insulin supply at low levels throughout the day and night. This insulin is supposed to keep your blood sugars as close to normal as possible when you are not eating. The rest of the insulin is given before meals, as so-called "bolus" or prandial insulin, which keeps your blood sugar levels in control after eating.

Benefits — Intensive insulin treatment is aimed at improved blood sugar control, which has been shown to improve how you feel on a daily basis and reduce your risk of health complications later in life.

Challenges — There are a few challenges to intensive insulin treatment:

You will need to coordinate your daily activities, what you eat, and how much and when you exercise, and you will need to check your blood sugar frequently (four or more times per day) or use a continuous glucose monitoring (CGM) device.

There is a risk of low blood sugar episodes, so you will need to learn how to prevent, recognize, and treat hypoglycemia. (See "Patient education: Hypoglycemia (low blood glucose) in people with diabetes (Beyond the Basics)".)

Some people gain weight initially, although exercise can counteract this effect.

Intensive insulin treatment is more expensive than simpler insulin treatment, although most states require insurance to at least partially cover insulin and the testing, treatment supplies, and devices that are necessary.

Staying motivated — Intensive treatment can be demanding, and some people lose motivation over time. Your diabetes health care team can provide tips and encouragement to help you stay on track. Helpful information and support is also available from the American Diabetes Association (ADA; http://www.diabetes.org/) at 800-342-2383 and the Juvenile Diabetes Research Foundation (JDRF; https://www.jdrf.org/t1d-resources/).

INJECTING INSULIN — Insulin is given as a shot under the skin (this is called a subcutaneous injection) using an insulin "pen" injector or a needle and syringe. Alternatively, insulin can be delivered with an insulin pump that uses a small tube, called a catheter, to give the insulin under the skin (see 'Insulin pump' below). The following figure demonstrates the sites where you can inject insulin (figure 2).

You and your parents or partner should learn to draw up and give insulin shots. Infants and very young children will need a parent or caregiver to give insulin, but most older children can give themselves injections.

Insulin pen injectors — Insulin pen injectors may be more convenient to carry and use, particularly when you are away from home. Most are approximately the size of a large writing pen and contain a cartridge that contains the insulin, a dial to set the dose, and a button to deliver the injection (figure 3). A new needle must be attached to the pen prior to each injection. The needles are sold separately from the pens. Insulin pen cartridges should never be shared, even if the needle is changed. The injection technique is similar to using a needle and syringe. (See 'Injection technique' below.)

Pens are especially useful for accurately injecting very small doses of insulin and may be easier to use if you have vision problems. Pens are generally more expensive than traditional syringes and needles. A number of different insulin pens are available; if your health care provider prescribes a pen for you, it will come with specific instructions for use.

Needle and syringe — You will use a needle and syringe to draw up insulin from a bottle (vial) and inject the insulin under the skin. The needle must be injected at the correct angle; injecting too deeply could deliver insulin to the muscle, where it may be absorbed too quickly. Injecting too shallowly deposits insulin in the skin, which is painful and reduces complete absorption.

The best angle for insulin injection depends upon your body type, where you are injecting, and the length of your needle. A doctor or nurse can show you the right angle of injection.

Drawing up insulin — There are many different types of syringes and needles, so it is best to get specific instructions on drawing up insulin from your doctor or nurse. Basic information is provided in the table (table 1). If you use an insulin pen, you should follow the instructions for dosing and giving insulin provided by the pen manufacturer and your doctor. (See 'Insulin pen injectors' above.)

Before drawing up insulin, it is important to know the dose and type of insulin needed. If more than one type of insulin is combined in one syringe, the person drawing up the insulin should calculate the total dose before drawing up the insulin. Some people, including young children and those with difficulty seeing or other disabilities, may need assistance. Devices to magnify the syringe markings and simplify the drawing up process are available.

One type of insulin, called U-500 insulin, requires a special U-500 syringe; this syringe makes it easier to measure the right dose. If you use this type of insulin, your doctor or pharmacist can show you how to use the U-500 syringe. It is very important to use this specially marked syringe only for U-500 insulin. Using a U-500 syringe with other insulins or using a U-100 syringe with U-500 can potentially result in dangerous errors in insulin dose.

Injection technique — The following is a description of subcutaneous insulin injection:

Choose the site to inject (figure 2). It is not necessary to clean the skin with alcohol unless the skin is dirty.

Pinch up a fold of skin and quickly insert the needle at a 90° angle (or other angle, as described above) (figure 4). Keep the skin pinched to avoid injecting insulin into the muscle. Depending upon your body type, you may not need to pinch up a fold of skin.

Push the plunger down completely to inject the insulin. Hold the syringe and needle in place for 5 to 10 seconds.

Release the skin fold.

Remove the needle from the skin.

If blood or clear fluid (insulin) is seen at the injection site, apply pressure to the area for five to eight seconds. The area should not be rubbed, because this can cause the insulin to be absorbed too quickly.

Needles and syringes should only be used once and then thrown away. Needles and syringes should never be shared. Used needles and syringes should not be included with regular household trash but should instead be placed in a puncture-proof container (also known as a sharps container), available from most pharmacies or hospital supply stores. Alternatively, a puncture-proof container such as an old liquid laundry detergent bottle, which can be closed with a screw cap, can be used. Check your local rules concerning disposal of these containers.

Injecting through clothing — Some people wonder about the safety of injecting insulin through their clothing. While it may be possible to do this, it's best to seek guidance from your health care provider if you are interested in using this technique.

Inhaled insulin — One formulation of inhaled insulin (brand name: Afrezza) is available for clinical use in the United States. Once inhaled, it begins to work quickly, similar to rapid-acting insulin, and is therefore considered a prandial (mealtime) insulin. Inhaled insulin has not been shown to lower glycated hemoglobin (A1C) levels to the usual target level of less than 7 percent in most studies. In addition, lung function testing is required before starting it and periodically during therapy.

Insulin pump

General principles — Insulin can be continuously administered by an insulin pump, rather than through multiple daily injections with a pen injector or needle and syringe. An insulin pump may be recommended based on your preference and willingness and ability to use it.

The pump stores rapid-acting insulin in a cartridge. Pumps are programmed to give a small dose of rapid-acting insulin every few minutes through the day and night (basal insulin). Before a meal, the pump needs to deliver a larger dose (bolus) of insulin, to prevent your blood sugar level from going too high after eating.

Most pumps deliver insulin through a long spaghetti-like catheter, the end of which you insert under the skin. The catheter is taken out and re-inserted approximately every two to three days. You will be taught how to do this relatively painless and quick procedure. Other pumps are entirely self-contained, with a small catheter built right into the small, disposable pump unit that needs to be replaced every few days. For these "patch" pumps, insulin delivery is controlled by another device that you need to carry with you. The pump can be taken off for up to one hour without impacting blood sugar control; if it is taken off for longer periods of time, insulin injections may be needed to control the blood sugar.

People using multiple daily insulin injections or an insulin pump may need to check their blood sugar levels four to seven times daily (before meals, bedtime, sometimes two to three hours after meals, and occasionally in the middle of the night) while their doses are being adjusted. In addition, testing is recommended when low blood sugar is suspected; before, during, and after exercise; and before driving or engaging in a dangerous activity. After doses are programmed initially in the pump, testing at least four times per day, including before meals, is required as you must direct the pump to give pre-meal insulin based upon your blood sugar level and amount and type of food you plan to eat. If insulin injection therapy is used, the pre-meal blood sugar is also used to help calculate the mealtime insulin dose injected.

The insulin pump is sometimes used in conjunction with a continuous glucose monitoring (CGM) device, which gives you more information about blood glucose levels than traditional fingersticks and a glucose meter. These devices allow you to make better informed decisions about insulin dosing based on the blood sugar trends. CGM can be used with insulin injection therapy or with insulin pump therapy (figure 5). Some insulin pumps automatically adjust the basal rate of insulin delivery depending on the CGM results (a partial "artificial pancreas"). These devices can improve or maintain glucose control with less risk of hypoglycemia.

The following devices, combining an insulin pump with CGM, are available or will become available in the future:

Sensor-augmented insulin pump – With these devices, you use the CGM readings to make adjustments in the insulin dosing. The insulin pump can be programmed to stop insulin delivery for up to two hours at a preset glucose value ("low glucose suspend" feature) or to reduce or stop insulin infusion if the system "predicts" that your blood sugar will soon go too low ("predictive low glucose suspend" feature). These features reduce the frequency and duration of hypoglycemia that may occur while you are sleeping.

Partially automated insulin pump (hybrid system) – The partially automated insulin pump is a hybrid system (not fully automated) in that only the basal insulin doses are automatically adjusted depending on CGM results. You need to manually request insulin doses prior to meals.

Fully automated insulin pump or bihormonal insulin pump – The bihormonal system uses two commercially available pumps, with one delivering insulin and the other glucagon. These systems are fully automated, in that the delivery of the insulin and glucagon is determined completely automatically by an algorithm that is, in turn, dependent on CGM results. These devices have not yet been approved and are not commercially available.

The insulin pump has advantages and disadvantages; it may be helpful to talk with a person who uses a pump before deciding to try it. Most pump manufacturers have a list of people willing to speak with prospective pump users. It may also be possible to use a trial pump for a few days before committing to it.

Advantages — Insulin pumps have the advantage of increasing flexibility in the timing of meals and other day-to-day events. This can be of great benefit for children or adults whose schedule varies from one day to the next. People who use an insulin pump do not require multiple daily injections; most people who use the pump change their injection (insulin infusion) site every 48 to 72 hours.

Another major advantage of an insulin pump is that there is less variation in the amount of insulin absorbed compared with when insulin is given with a needle and syringe or pen. This can help reduce day-to-day variations in blood sugar levels. Insulin pumps can deliver smaller amounts of insulin at a time than injection therapy.

Disadvantages — The cost of an insulin pump and supplies is greater than the cost of insulin syringes and needles or pens, although most insurance carriers cover some portion of the expenses. Some people develop pump-associated problems, including skin infection at the infusion site or pump malfunction.

You must take care to monitor your blood sugar levels carefully; stopping insulin, even for a short time, can lead to a significant increase in blood sugar. Some people find the pump awkward, unpleasant, or embarrassing (although others find that they are able to adjust to it fairly easily). However, you can disconnect the pump for brief periods, if desired.

FACTORS AFFECTING INSULIN ACTION — Several factors can affect how insulin is absorbed.

Dose of insulin injected — The dose of insulin injected affects the rate at which your body absorbs it. For example, larger doses of insulin may be absorbed more slowly than a small dose. With larger doses of insulin, the insulin may peak later or last longer than with small doses. This could mean that your blood sugar level is higher than expected within a few hours after eating but then becomes low.

Injection technique — The angle and depth of an insulin injection are important, as mentioned above. (See 'Needle and syringe' above.)

Site of injection — Clinicians usually recommend changing your injection site to minimize tissue irritation. However, it is important to keep in mind that insulin is absorbed at different rates in different areas of the body. For some types of insulin, the insulin is absorbed fastest from the abdominal area, slowest from the leg and buttock, and at an intermediate rate from the arm. This may vary with the amount of fat under the skin; the more fat, the more slowly insulin is absorbed (figure 2).

Because of variations in absorption, it is reasonable to use the same general area for injections at a particular time of the day. Pre-meal insulin injections are absorbed fastest from the abdominal area, allowing for optimal coverage of carbohydrates consumed in a meal. Injection into the thigh or buttock may be best for the evening dose because the insulin will be absorbed more slowly during the night.

Subcutaneous blood flow — Any factor that alters the rate of blood flow to the body's tissues will alter insulin absorption. Smoking decreases blood flow to the tissues and decreases absorption of injected insulin. In contrast, factors that increase the skin temperature (such as exercise, saunas, hot baths, and massage of the injection site) will increase insulin absorption.

Time since opening the insulin bottle or pen — In general, insulin bottles (vials), pens, and pen cartridges are good until their expirations date, if left unopened in a refrigerator. Insulin should never be allowed to freeze or get hot.

Once an insulin bottle (vial) is opened, it should be kept at room temperature or in the refrigerator for 28 to 30 days and then discarded. After a month, the potency begins to decrease. This can be a problem for people who require very small doses of insulin, for whom a bottle might last two months or more. In general, it is advisable to open a new bottle at least every 30 days, even if there is insulin left in the old bottle. However, a few types of insulin can be used for up to 42 days, so check with your pharmacist or health care provider.

For insulin pen devices, it is acceptable to keep the pen injector unrefrigerated (in a bag or jacket pocket) for varying amounts of time, depending upon the type of pen. Most opened insulin pens can be used for either 10, 14, or 28 days, but there are some pens that can be used for 42 or 56 days, depending upon the type of insulin in the pen. Be sure you know how long your type of insulin pen is safe to use after opening.

Individual factors — The same dose of the same type of insulin may have different effects in different people with diabetes. Some trial and error is usually necessary to find the ideal type(s) and dose of insulin and schedule for each person.

SPECIAL SITUATIONS — Several special situations can complicate insulin treatment. With advance planning and close monitoring, these situations are less likely to cause serious difficulties. A health care provider can help to handle these situations.

Eating out — Eating out can be challenging since ingredients used, calorie and fat content, and portion sizes are usually different from meals prepared at home. You can estimate the carbohydrate content of meals to calculate insulin dose; nutrition information is often available from restaurants, a handheld or online reference book, or mobile phone app.

Low or high blood sugar levels can occur more easily in situations where new or different foods are eaten; a fast-acting source of carbohydrates (eg, candy, glucose tablets) and a blood glucose monitor should be kept on hand at all times. (See "Patient education: Type 1 diabetes and diet (Beyond the Basics)".)

Surgery — If you are planning to have surgery, you may be instructed not to eat for 8 to 12 hours before the procedure. A health care provider can help to determine the dose and timing of insulin to use before and after the procedure. This is particularly important if you will be unable to eat a normal diet for a time afterwards.

Infections — Infections (such as a cold, sore throat, urinary tract infection, or any infection that causes fever) can cause blood sugar levels to rise and can even lead to a serious problem called diabetic ketoacidosis (DKA). DKA happens when the body's lack of insulin makes it unable to use glucose (sugar) for energy. The body then burns fat as an energy source, which causes the buildup of acids in the blood called "ketones." This is dangerous and requires immediate treatment.

If you get sick, it's a good idea to talk with your health care provider, as you will need to carefully monitor your blood sugar levels and possibly increase your insulin dose. It is also important to drink plenty of fluids in order to avoid dehydration. If you have nausea or vomiting, you may need medication to control your symptoms and avoid dehydration and ketoacidosis. Your provider can also talk to you about how and when to check for ketones (the acids produced in the body when the body needs more insulin).

Travel — Managing blood sugar levels and insulin treatment while traveling can be difficult, especially when traveling across multiple time zones. In addition, activity levels and diet are often different while traveling, making careful blood sugar monitoring essential. Speak with your health care provider before traveling to develop a treatment plan. (See "Patient education: General travel advice (Beyond the Basics)", section on 'Traveling with medical conditions'.)

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Type 1 diabetes (The Basics)
Patient education: Using insulin (The Basics)
Patient education: Should I switch to an insulin pump? (The Basics)
Patient education: Low blood sugar in people with diabetes (The Basics)
Patient education: Care during pregnancy for people with type 1 or type 2 diabetes (The Basics)
Patient education: My child has diabetes: How will we manage? (The Basics)
Patient education: Controlling blood sugar in children with diabetes (The Basics)
Patient education: Managing diabetes in school (The Basics)
Patient education: Giving your child insulin (The Basics)
Patient education: Checking your child's blood sugar level (The Basics)
Patient education: Carb counting for children with diabetes (The Basics)
Patient education: Diabetic ketoacidosis (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Type 1 diabetes: Overview (Beyond the Basics)
Patient education: Blood glucose monitoring in diabetes (Beyond the Basics)
Patient education: Type 1 diabetes and diet (Beyond the Basics)
Patient education: Hypoglycemia (low blood glucose) in people with diabetes (Beyond the Basics)
Patient education: Care during pregnancy for women with type 1 or 2 diabetes (Beyond the Basics)
Patient education: General travel advice (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Effects of exercise in adults with diabetes mellitus
Measurements of glycemic control in diabetes mellitus
General principles of insulin therapy in diabetes mellitus
Glycemic control and vascular complications in type 1 diabetes mellitus
Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control
Inhaled insulin therapy in diabetes mellitus
Management of blood glucose in adults with type 1 diabetes mellitus
Hypoglycemia in adults with diabetes mellitus
Nutritional considerations in type 1 diabetes mellitus
Overview of general medical care in nonpregnant adults with diabetes mellitus
Pancreas and islet transplantation in diabetes mellitus
Perioperative management of blood glucose in adults with diabetes mellitus
Prevention of type 1 diabetes mellitus
Approach to the adult with brittle diabetes or high glucose variability

The following organizations also provide reliable health information.

National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)

National Institute of Diabetes and Digestive and Kidney Diseases

(www.niddk.nih.gov/)

American Diabetes Association (ADA)

(800)-DIABETES (800-342-2383)
(www.diabetes.org)

Canadian Diabetes Associates

(www.diabetes.ca)

Juvenile Diabetes Research Foundation

(www.jdrf.org)

US Centers for Disease Control and Prevention

(www.cdc.gov/diabetes)

This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms ©2022 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.
Topic 1738 Version 22.0