INTRODUCTION — Type 2 diabetes mellitus occurs when the pancreas (an organ in the abdomen) produces insufficient amounts of the hormone insulin and/or the body's tissues become resistant to normal or even high levels of insulin. This causes high blood glucose (sugar) levels, which can lead to a number of complications if untreated.
People with type 2 diabetes require regular monitoring and ongoing treatment to maintain normal or near-normal blood glucose levels. Treatment includes lifestyle adjustments, self-care measures, and medications, which can minimize the risk of diabetes-related and cardiovascular complications (eg, heart attacks and strokes). Learning to manage diabetes is a process that continues over a lifetime. The diagnosis of diabetes can be overwhelming at the beginning; however, most people are able to lead normal lives and many patients become experts in their own care.
This topic review discusses the role of insulin in blood glucose control for patients with type 2 diabetes. Separate topic reviews about other aspects of type 2 diabetes are also available. (See "Patient information: Diabetes mellitus; type 2" and see "Patient information: Self-blood glucose monitoring" and see "Patient information: Hypoglycemia (low blood glucose) in diabetes" and see "Patient information: Lifestyle modifications in type 2 diabetes" and see "Patient information: Preventing complications in diabetes mellitus").
IMPORTANCE OF BLOOD GLUCOSE CONTROL — Keeping blood glucose levels in control is one way to decrease the risk of complications related to type 2 diabetes. The most common complication of type 2 diabetes is heart disease, also known as macrovascular disease. Macro- means large, and vascular means vessels. Untreated heart disease increases the risk of heart attack.
Individuals with type 2 diabetes are also at increased risk of developing microvascular (small vessel) disease of the eyes, kidneys, and nerves, which can result in blindness, kidney failure, foot ulcers requiring amputation, and impotence in men. Microvascular and macrovascular complications usually occur after many years of diabetes and are related to elevated levels of blood glucose over time. However, these complications may be present when type 2 diabetes is first diagnosed due to a delay in seeking medical care.
One of the largest studies to examine the benefit of tight blood glucose control was the United Kingdom Prospective Diabetes Study (UKPDS). It demonstrated that strict glycemic control in patients with type 2 diabetes reduces the risk of microvascular disease. It is not clear if blood glucose control affects the risk of macrovascular complications [1]. However, other therapies are available to decrease these risks. (See "Patient information: Preventing complications in diabetes mellitus").
Monitoring — Most people with type 2 diabetes need to monitor their blood glucose levels at home. This is especially true if the person uses a medication for diabetes that can cause low blood glucose levels (eg, insulin).
Blood glucose control is often measured by checking the blood glucose level before the first meal of the day (fasting). A normal fasting blood glucose level is less than 100 mg/dL (5.6 mmol/L), although some people will have a different goal. A healthcare provider can help to determine this goal with the patient. Some people will need to test their blood glucose level before and/or after other meals during the day. The frequency of testing and blood glucose goals can change over time, so periodic visits to discuss these issues are important. (See "Patient information: Self-blood glucose monitoring").
Blood glucose control can also be measured with a blood test called A1C. The A1C blood test measures the average blood glucose level during the past two to three months. The test is done by giving a small sample of blood from a vein or fingertip in a clinician's office. The goal A1C for most people with type 2 diabetes is less than 7 percent, which corresponds to an average blood glucose of 150 mg/dL (8.3 mmol/L, show table 1). A healthcare provider can determine a person's individual A1C goal.
The average blood glucose goal (150 mg/dl or 8.3 mmol/L) is higher than the fasting blood glucose goal (100 mg/dL or 5.6 mmol/L) for several reasons. Blood glucose levels increase after eating. The amount and speed of the increase depend upon the type and amount of food eaten at a particular meal. The increase also depends upon the type and dose of diabetes treatment(s) used and the person's activity level.
How often to see your clinician — Most patients with type 2 diabetes meet with their healthcare provider every three to four months; blood glucose levels and medications, including insulin dosing, are reviewed at these visits, helping patients to fine-tune their diabetes control.
TREATMENT OPTIONS — Most people who are newly diagnosed with type 2 diabetes are usually treated with a combination of diet, exercise, and an oral medication (eg, pills). Some oral medications (eg, metformin) improve the body's response to insulin. Other medications cause the body to produce more insulin. (See "Patient information: Diabetes type 2: Treatment").
A second medication may be added within the first two to three months if blood glucose control is not adequate. "Adequate" control is defined as an A1C level less than 7 percent for most people; insulin may be recommended early if the A1C remains elevated despite lifestyle changes and diabetes pills, especially if the A1C is higher than 8.5 percent.
The need for a second medication is not uncommon [2]. Type 2 diabetes typically progresses with age, causing the body to produce less insulin and resist the action of insulin that is produced. In addition, it can be difficult for some people to follow the recommended diet, exercise, or treatment plan. Being diagnosed with a new medical problem or requiring a new medication can also change the body's needs for insulin, sometimes requiring a change in diabetes treatment. For example, when a person with type 2 diabetes takes corticosteroids (eg, prednisone) for an asthma attack, the blood glucose levels increase. This usually requires a higher dose of diabetes medication.
Oral medication plus insulin — Some people with type 2 diabetes require only oral medications for treatment. Other people will need to add insulin because their blood glucose levels are not controlled. Using a combination of treatments (oral medication plus insulin) generally means that the patient can take a lower dose of insulin, compared to if insulin treatment is used alone. There may also be a reduced risk of weight gain if combination therapy is used.
Insulin is usually given once per day, either in the morning or at bedtime. Small insulin doses are generally recommended when treatment first begins; the dose is adjusted over days, weeks, and months, once the body's response to insulin treatment is known.
To determine how and when to adjust the dose, the blood glucose level should be measured every morning before eating. If the value is consistently higher than 130 mg/dL (7.2 mmol/L), the clinician may recommend increasing the insulin dose. (See "Patient information: Self-blood glucose monitoring").
Insulin alone — Current recommendations are for most people with type 2 diabetes to be treated with metformin plus another medication such as insulin, as necessary. However, for a variety of reasons, some people are treated only with insulin. People taking insulin alone often require two injections of intermediate-acting insulin or one injection of long-acting insulin per day (see "Types of insulin" below). (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").
If a long-acting insulin or a twice daily injection of intermediate-acting insulin is not adequate to control blood glucose levels, a more intensive insulin treatment regimen may be recommended. Intensive insulin treatment requires at least two injections of insulin per day, usually including a rapid-acting and long-acting insulin, or the use of an insulin pump. It also requires that the person monitor their blood glucose levels several times per day. This is discussed in greater detail in a separate topic review. (See "Patient information: Diabetes type 1: Insulin treatment", section on intensive insulin treatment).
TYPES OF INSULIN — 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 (show table 2):
Injectable insulin 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®])
The various types of insulin can be used in combination to achieve around-the-clock blood glucose control.
Inhaled insulin — An inhaled form of rapid-acting insulin is available, although it is not yet in common use. Inhaled insulin may be used in combination with long-acting insulin injections. The main issue with this new treatment is that it is difficult to make adjustments in the dose. Patients interested in using this type of insulin should talk with their health care provider.
INSULIN ADMINISTRATION — Insulin cannot be taken in pill form. It 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. The site also determines how quickly the insulin is absorbed. (See "Site of injection" below).
Drawing up insulin — There are many different types of syringes and needles, so it's best to get specific instructions for drawing up insulin from a healthcare provider. Basic information is provided in the table (show table 2). Persons using an insulin pen should follow the instructions 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; persons using more than one type of insulin should calculate the total dose needed before drawing up their insulin. Some persons, including children and those with difficulty seeing, may need assistance. Magnification and other assistive devices are available. People who have difficulty drawing up their insulin should discuss this with their clinician.
Injection angle — Insulin is usually injected under the skin using a needle and syringe (show figure 2). It is important to use the correct injection angle since injecting too deeply could deliver insulin to the muscle, where it is absorbed too quickly. On the other hand, injections that are too shallow are more painful and not absorbed well.
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.
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 five 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 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 be used once and then thrown away; needles become dull quickly, potentially increasing the pain of injection. 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 [3]. 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 are available and 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 an option in some situations.
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.
OTHER FACTORS AFFECTING INSULIN ACTION — Several factors can affect how injected insulin works.
Dose 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 smaller doses.
Site of injection — Clinicians usually recommend rotating injection sites to minimize tissue irritation. When changing sites, 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 fat present; areas with more fat under the skin absorb insulin more slowly (show figure 1).
It is reasonable to use the same general area for injections given at the same time of the day. Sometimes abdominal injections, which are absorbed more quickly, are preferred before meals. Injection into the thigh or buttock may be best for the evening dose because the insulin will be absorbed more slowly during the night.
Smoking and physical activity — Any factors that alter the rate of blood flow through the skin and fat will change insulin absorption. Smoking decreases blood flow. In contrast, factors that increase blood flow (such as exercise, saunas, hot baths, and massage of the injection site) increase insulin absorption. To avoid low blood sugar, insulin injections should be given after a bath or sauna. It is best to inject insulin into the arm or abdomen and wait 30 minutes before running. A lower dose of insulin may be recommended before or after exercise; this should be discussed with a healthcare provider.
Time since opening the bottle — Most insulin remains potent and effective for up to a month after the bottle has been opened (if kept in the refrigerator between injections). However, the potency of intermediate and long acting insulin begins to decrease after 30 days. This can be a problem for people who require very small doses of insulin, for whom a bottle might last two months or more. It is advisable to start a new bottle at least every 30 days.
For very rapid acting insulin used in pen injectors, it is acceptable to keep the pen injector at room temperature (in a purse 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 differences — 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.
Insulin needs often change over a person's lifetime. Changes in weight, diet, health conditions (including pregnancy), activity level, and occupation can have an impact on the amount of insulin needed to control blood glucose levels. Patients are often able to adjust their own insulin dose, but may require assistance in some situations. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes").
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 their insulin needs in several ways, including nutrition information 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. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").
Surgery — Patients who undergo surgery may be instructed not to eat for eight 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. In this situation, frequent telephone contact with a healthcare provider, careful blood glucose monitoring, and increasing the insulin dose are often recommended. It is important to drink an adequate amount of fluids while ill to avoid dehydration. Patients with nausea or vomiting may require medication to control their symptoms and avoid dehydration.
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).
STAYING MOTIVATED — Living with diabetes 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. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837.
2. Turner, RC, Cull, CA, Frighi, V, Holman, RR for the UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes. Progressive requirement for multiple therapies (UKPDS 49). JAMA 1999; 281:2005.
3. Fleming, DR, Jacober, SJ, Vandenberg, MA, et al. The safety of injecting insulin through clothing. Diabetes Care 1997; 20:244.
4. Yki-Järvinen, H, Dressler, A, Ziemen, M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. Diabetes Care 2000; 23:1130.
5. Taylor, R, Davies, R, Fox, C, et al. Appropriate insulin regimes for type 2 diabetes: a multicenter randomized crossover study. Diabetes Care 2000; 23:1612.
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