Tuesday, October 16, 2007

Diabetes type 1: Insulin treatment

INTRODUCTION — Diabetes mellitus is a lifelong condition that can be controlled with lifestyle adjustments and medical treatments. Keeping blood glucose levels under control can prevent or minimize complications. Insulin treatment is one component of a diabetes treatment plan that is necessary for all persons with type 1 diabetes.

Insulin treatment replaces or supplements the body's own insulin, restoring normal or near-normal blood glucose control. Many different types of insulin treatment can successfully control blood glucose 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 glucose under control. (See "Patient information: Diabetes mellitus, type 2" and see "Patient information: Diabetes mellitus, type 1").

GOALS OF INSULIN TREATMENT — The goal of insulin treatment is to keep blood glucose levels at normal or near-normal levels. Careful control of blood glucose levels can help prevent both the short-term effects of poorly controlled blood glucose (such as diabetic ketoacidosis) and the long-term effects of poorly controlled blood glucose (diabetic complications of the eye, kidney, and cardiovascular system).

STARTING INSULIN — The pancreas produces very little or no insulin at all in people with type 1 diabetes. Some people have a "honeymoon" period soon after their diagnosis when insulin is not needed. Although it is tempting to stop insulin during this period, continuing insulin may preserve the person's ability to produce insulin for many months or years, making diabetes easier to control. All patients with type 1 diabetes will eventually require insulin.

Regimens — There are two general types of insulin treatment plans: standard (conventional) insulin treatment and intensive insulin treatment. They differ with regard to the type(s) and dose of insulin and the number of injections per day. In general, intensive insulin therapy is recommended for patients with type 1 diabetes (see "Intensive insulin treatment" below). Standard insulin treatment is an older regimen, although it may still be recommended for selected patients.

Dosing — When insulin treatment is started, small doses are generally recommended; the dose is adjusted over days, weeks, and months, once the body's response to insulin treatment is known. During this time, the patient must monitor the blood glucose level several times per day to determine the optimal dose of insulin.

Insulin needs often change over a person's lifetime. Changes in weight, diet, health conditions (including pregnancy), activity level, and occupation can affect the amount of insulin needed to control blood glucose levels. Patients are often able to adjust their own insulin dose, but most people require assistance in some situations. Most patients with type 1 diabetes meet with their healthcare provider every three to four months; blood glucose levels and insulin doses are reviewed at these visits, helping patients to fine-tune their diabetes control. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes").

Types — There are several different types of insulin. These types are classified according to how quickly they begin working and how long the insulin remains active (show table 1): Rapid-acting (eg, insulin lispro [Humalog®], insulin aspart [Novolog®], and insulin glulisine [Apidra®]) Short-acting (eg, insulin regular) Intermediate-acting (eg, insulin NPH) Long-acting (eg, insulin glargine [Lantus®], insulin detemir [Levemir®])

Insulin types can be used in combination to achieve around-the-clock blood glucose control.

INSULIN ADMINISTRATION — Insulin is ineffective when taken orally, and must therefore be given by other routes. Insulin is usually injected into the layer of fat under the skin (called subcutaneous injection). The following figure demonstrates the sites where insulin may be injected (show figure 1).

Patients as well as parents or partners should learn to draw up and inject insulin. An inhaled form of insulin is also available, although its role has not yet been fully defined (see "Inhaled insulin" below).

Needle and syringe — A needle and syringe are usually used to draw up and inject insulin under the skin. The needle must be injected at the correct angle since injecting too deeply could deliver insulin to the muscle, where it is absorbed quickly. Injecting too shallowly deposits insulin in the skin, which is painful and prevents the body from absorbing the insulin.

The best angle for insulin injection depends upon a patient's body type, injection site, and length of the needle used. A healthcare professional can help determine the right angle of injection.

Drawing up insulin — There are many different types of syringes and needles, so it's best to get specific instructions from a healthcare provider. Basic information is provided in the table. Persons using an insulin pen should follow the instructions for dosing and administration provided by the pen manufacturer and their clinician (see "Insulin pen injectors" below).

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

Injection technique — The following is a description of subcutaneous insulin injection. Choose the site to inject (show figure 1). 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 90º angle (or other angle, as described above, show figure 2). Keep the skin pinched to avoid injecting insulin into the muscle. Push the plunger down completely to inject the insulin. Hold the syringe and needle in place for 5 seconds. Release the skin fold. Remove the needle from the skin.

If blood or clear fluid (insulin) is seen at the injection site, the patient should apply pressure to the area for 5 to 8 seconds, but the area should not be rubbed.

Needles and syringes should only be used once and then thrown away. 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.

Some patients wonder about the safety of injecting insulin through their clothing. One small study examined the risks and benefits of this technique, and found that blood glucose control did not differ between the group that injected insulin through a single layer of clothing and those that injected directly into the skin [1]. There were no reports of infections in either group, although a few patients who injected through clothing reported blood stains on their clothing or bruises on the skin. People who are interested in using this technique should speak with their healthcare provider before trying it.

Insulin pen injectors — Insulin pen injectors may be more convenient to carry and use when away from home. Most are approximately the size of a large writing pen, and contain a disposable insulin cartridge and needle. Some types of insulin and some insulin mixtures are not available in cartridges, meaning pens may not be used by all persons.

Pens are especially useful for accurately injecting very small doses of insulin, and may be helpful for persons with impaired vision. Pens are generally more expensive than traditional syringes and needles. A number of insulin pens are available, and the specific instructions for use of each type should be obtained from the manufacturer or a healthcare provider.

Inhaled insulin — An inhaled form of rapid-acting insulin is available; it is usually combined with long-acting insulin that is injected. When insulin is inhaled, the onset of action is rapid; slightly faster than a subcutaneous injection of rapid acting insulin (like lispro, aspart or glulisine). However, the duration of action is longer.

A problem with inhaled insulin is that about 90 percent of the dose is lost in the mouth and upper airways. As a result, several companies are developing devices to improve delivery to the lungs, where it can be better absorbed.

The 1 mg blister of insulin (Exubera®) delivers the equivalent of about 2.7 units of insulin while the 3 mg blister delivers the equivalent of about 8 units of insulin. Thus, it is not suitable if small adjustments in dose are needed.

Inhaled insulin is not suitable for patients who have asthma. It can reduce lung function and causes cough in about 20 percent of people; periodic lung testing is recommended. None of these side effects are considered to be major problems.

There are no guidelines in the United States regarding the use of inhaled insulin. It is significantly more expensive that injected insulin, and in clinical studies, it does not improve blood glucose control compared to injected insulin.

Insulin pump — Insulin can be continuously administered by insulin pump, a process called continuous subcutaneous insulin infusion. An insulin pump may be recommended for patients who are willing to closely monitor their blood glucose levels, food intake, and other factors.

The pump is worn externally and is attached to the body with long, thin, flexible plastic tubing that has a needle or soft cannula (thin plastic tube), which is inserted and then left in place beneath the skin. The needle or cannula and tubing are changed every 48 to 72 hours by the patient. The pump stores rapid acting insulin in a cartridge. The pump is programmed to give a small dose of insulin continuously through the day and night. At meal times, the patient must program the pump to give an additional dose of insulin, based upon the amount of food to be eaten. The pump can be taken off for up to one hour without impacting blood glucose control; if it is taken off for longer periods of time, insulin injections are needed to maintain blood glucose control.

The insulin pump has advantages and disadvantages; it may be helpful to talk with a person who uses a pump before deciding to purchase 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 permit flexibility in the timing of meals and other day-to-day events, similar to intensive treatment regimens that combine very-rapid acting and long-acting insulins. 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 patients who use the pump change their injection site every 48 to 72 hours.

The other major advantage of an insulin pump is that day-to-day variation in insulin absorption is greatly reduced compared to conventional injections of intermediate or long acting insulins. This can help reduce day-to-day variation in blood glucose levels.

Disadvantages — The cost of an insulin pump and supplies is greater than the cost of insulin syringes and needles, although most insurance carriers cover some portion of the expenses. Many patients who use a pump develop pump-associated problems, including infection at the injection site or pump malfunction; patients must take care to monitor blood glucose levels carefully since even a temporary disruption can lead to serious elevations in blood glucose. Some find the pump awkward, uncomfortable, or embarrassing; 30 percent of people who begin using a pump discontinue its use within five years.

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

Volume of insulin injected — The dose of insulin injected affects the rate at which the body absorbs it. 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 the patient's blood glucose level is higher than expected within a few hours after eating, but then becomes

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 rotating injection sites 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. 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 subcutaneous fat present; the greater the amount of subcutaneous fat, the more slowly insulin is absorbed (show figure 1).

Because of anatomic variations in absorption, it is reasonable to use the same general area for injections given at the same 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 factors that alter the rate of blood flow to the subcutaneous tissue will alter insulin absorption. Smoking actually decreases blood flow to the subcutaneous tissue 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 bottle — While most insulin remains potent and effective for up to a month after the bottle has been opened (if kept in the refrigerator between injections) the potency for intermediate or long acting insulin begins to decrease after 30 days. This can be a problem for people who require very small doses of insulin and for whom a bottle might last two months or more. It is advisable to start a new bottle at least every 30 days.

For rapid acting insulin used in pen injectors, it is acceptable to keep the pen injector unrefrigerated (in a bag or jacket pocket) for up to 14 days, provided that the pen is not exposed to temperature extremes. However, after 14 days, a new insulin cartridge or pen should be used, even if there is insulin left in the old cartridge.

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 for a person with diabetes. With advance planning and careful calculation, these situations are less likely to cause serious difficulties. A healthcare provider can assist patients in handling 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. Patients can estimate the carbohydrate content of meals to calculate insulin dosage; nutrition information is often available from restaurants or a hand-held reference book. Hypo- and hyperglycemia can occur more easily in situations where new or different foods are eaten; thus patients should keep a fast-acting source of carbohydrates and blood glucose monitor on hand at all times.

Surgery — Patients who undergo surgery may be instructed not to eat for 8 to 12 hours before their procedure. A healthcare provider can help to determine the dose and timing of insulin before and after the procedure, especially if a patient will be unable to eat a normal diet afterwards.

Infections — Mild infections, such as a cold, sore throat, or urinary tract infection, can cause blood glucose levels to rise and can even lead to diabetic ketoacidosis. In this situation, frequent telephone contact with a healthcare provider, careful blood glucose monitoring, and increasing the insulin dose are often recommended. Patients with nausea or vomiting may require medication to control their symptoms and avoid dehydration and ketoacidosis. If dehydration occurs, intravenous fluid replacement may be necessary.

Travel — Managing blood glucose 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 glucose monitoring essential. Patients should speak with their healthcare provider before traveling to develop a treatment plan. (See "Patient information: General travel advice" section on "Traveling with medical conditions").

INTENSIVE INSULIN TREATMENT — Intensive insulin treatment refers to treatment that tightly controls blood glucose levels; this treatment can achieve better control than standard insulin therapy regimens. Intensive insulin treatment requires multiple subcutaneous insulin injections or the use of an insulin pump in addition to frequent monitoring of blood glucose levels.

Most people with type 1 diabetes are candidates for intensive treatment; patients may begin when they are diagnosed or at a later time. Because it requires a serious commitment of time and effort, patients and families should learn as much as possible about intensive treatment before committing to it.

Benefits — Intensive insulin treatment can improve control of blood glucose, which can improve how a patient feels on a daily basis as well as reduce their risk of health complications later in life. A landmark study, the Diabetes Control and Complications Trial (DCCT) conclusively proved that the improved blood sugar control that results from intensive therapy means fewer long-term complications of diabetes.

Drawbacks — There are a few drawbacks to intensive insulin treatment: It requires careful management of daily activities, dietary intake, frequent insulin administration, exercise, and blood glucose monitoring (performed four to seven times per day). There is a three-fold increased risk of hypoglycemic episodes. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes"). Some patients gain weight (an average of about 10 pounds) initially, although exercise can counteract this effect. It is about three times as expensive as standard insulin treatment.

Staying motivated — Intensive treatment can be very demanding and some patients lose motivation over time. Healthcare providers can provide tips and encouragement to help patients stay on track. Helpful information and support is also available from the American Diabetes Association (ADA), at (800)-DIABETES (800-342-2383) and at www.diabetes.org.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. 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)
U.S. Center for Disease Control and Prevention

(www.cdc.gov/diabetes)


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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Fleming, DR, Jacober, SJ, Vandenberg, MA, et al. The safety of injecting insulin through clothing. Diabetes Care 1997; 20:244.
2. Holman, RR, Turner, RC. A practical guide to basal and prandial insulin therapy. Diabet Med 1985; 2:45.
3. Yki-Jarvinen, H, Kauppila, M, Kujansuu, E, et al. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 1992; 327:1426.
4. Koivisto, VA, Felig, P. Alterations in insulin absorption and in blood glucose control associated with varying insulin injection sites in diabetic patients. Ann Intern Med 1980; 92:59.
5. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329:977.

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