Sunday, October 21, 2007

Depression in adults

INTRODUCTION — Depression is a medical condition characterized by a wide variety of psychological and physical symptoms. Extreme sadness is often the most pronounced symptom. Depression is differentiated from occasional blues and from grief (a normal reaction to loss) by its persistence and its interference with daily activities and relationships.

In the past, depression was poorly understood and carried an unfortunate social stigma. Depression is common; the risk of suffering from a major depressive episode at some time during life is up to 12 percent for men and 25 percent for women. The condition can affect people of all ages, including children and older adults.

Depression is a treatable condition. Psychotherapy (counseling), drug therapy, and other treatments can alleviate symptoms and help people with depression return to rich and productive lives. Treatment is most successful in persons who are receptive to and participate in their treatment. Persons with depression should work closely with a clinician to ensure that treatment is effective.

CAUSE OF DEPRESSION — Research has helped clarify the complex biologic basis of depression, although the exact cause of depression is still uncertain. Studies suggest that depression results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions. That depression represents an actual biologic disorder is supported by the results of genetic studies and the response of depression to drug therapy and other therapies that alter levels of brain neurochemicals.

RISK FACTORS — Although anyone can develop depression, certain factors increase a person's risk for this condition, including: Female gender A history of depression in a first degree relative (parent, sibling, or child) A prior episode of major depression

Other factors have been identified as secondary (weaker) risk factors for depression: A history of depression in a family member who is not a first degree relative Lack of social supports Significant stressful life events Current alcohol or substance abuse

SYMPTOMS/DEFINITIONS — Extreme sadness may be a symptom of depression, although depression can cause other psychological and physical symptoms. The hallmark of depression is that these symptoms are persistent and interfere with daily activities and relationships.

Unfortunately, there is no single sign or symptom that serves as a marker for depression, and the condition can be tricky to identify. In fact, many people do not recognize that they are depressed or that their physical symptoms (aches and pain, appetite and sleep changes) are related to depression. One study revealed that 29 percent of people visiting their doctors for a physical symptom had a depressive disorder or an anxiety disorder [1].

The symptoms of depression for the three distinct types of depression (major depression, dysthymia, and atypical depression) will be discussed here.

Major depression — The diagnosis of major depression is based upon the presence of at least five of nine symptoms: Sadness most of the day, particularly in the morning Markedly diminished pleasure or interest in almost all activities nearly every day Significant weight loss or weight gain Insomnia or excessive sleep Agitated movements or very slow movement Fatigue or loss of energy Feelings of worthlessness or guilt Impaired concentration and indecisiveness Recurring thoughts of death or suicide

The symptoms must be present during the same time period and must persist for at least two weeks. One of the symptoms must be either depressed mood or loss of interest.

Dysthymia — Dysthymia is a low-grade depression that persists for a long period of time. Dysthymia is usually diagnosed when a person has had depressive symptoms for at least two consecutive years. The prominent symptoms of dysthymia include an absence of pleasure or interest in activities, low self-esteem, and low energy.

Atypical depression — Atypical depression is the most common type of depression seen in a primary care setting. People with atypical depression have some of the same features of major depression listed above, but do not have five of the nine symptoms required for a diagnosis of major depression. Instead, they often have prominent physical symptoms, including weight gain and sleep disturbances, especially excessive sleep.

Seasonal affective disorder — Seasonal affective disorder (SAD) is a form of major depression that varies with the seasons. Most patients with SAD have episodes of depression that begin in the fall and continue through the winter.

SAD is characterized by several features: Symptoms of depression that regularly appear during a particular time of year (unrelated to stressful events associated with specific seasons) Full remission of depression (or a change from depression to mania) during other times of year Two major episodes of depression during the associated season in the last two years and an absence of depression during other times of the year

Grief — Grief is a normal reaction to many situations, following the death of a loved one, loss of a close relationship or job, or the loss of health or independence. This section discusses one of the most common types of grief that occurs after the death of a family member or friend.

Grief following death — Immediately following death, whether or not the death has been anticipated, survivors usually experience feelings of numbness, shock, and disbelief. Intense feelings of sadness, yearning for the deceased, anxiety about the future, disorganization, and emptiness commonly arise in the weeks after the death.

"Searching behaviors," including visual and auditory hallucinations of the deceased person, are common and may lead the bereaved person to fear that he or she is "going crazy." Despair and sadness are common as it becomes clear that the deceased will not return. Sleeplessness, appetite disturbances, agitation, chest tightness, sighing, and exhaustion are common.

These reactions are usually transient and resolves in over 90 percent of people by 13 months after the loss. However, losses can trigger depression in some people; as an example, 15 to 35 percent of people who lose their spouse develop depression in the following year [2].

Some patients who grieve may develop complicated grief (or traumatic grief), which is defined as persistence of at least four of the following feelings for six months or more: Numbness/detachment Bitterness Feelings that life is empty without the deceased Trouble accepting the death A sense that the future holds no meaning without the deceased Being on edge or agitated Difficulty trusting others since the loss

Grief versus depression — It is often difficult to know if a person who is grieving also suffers from depression. Patients who have feelings of hopelessness, helplessness, worthlessness, and guilt, as well as severe symptoms of early grief may be depressed. Patients whose grief is complicated by depression often benefit from an antidepressant medication in addition to individual or group psychotherapy. Group therapy in a bereavement group can be particularly useful for patients with grief and depression. In contrast, persons suffering only with grief are more likely to benefit from psychotherapy alone.

Bipolar depression — People with bipolar disorder (manic depression) have depression as part of the syndrome. Bipolar II disorder is relatively common and involves periods of depression interspersed with periods of "hypomania," which are prolonged periods (weeks to months) of high energy, decreased sleep, and some agitation. People with bipolar II disorder may have a poor or agitated response to antidepressant medications; a psychiatrist is recommended to assist in the treatment of people with this disorder. (See "Patient information: Bipolar disorder").

DIAGNOSIS — The diagnosis of depression is based upon a patient's symptoms, the duration of symptoms, and the overall effects of these symptoms on a patient's life. There is currently no medical test that identifies depression, although blood tests are often done to rule out other medical conditions that could be causing depression (such as hypothyroidism).

A diagnosis of major depression requires that symptoms are severe enough to interfere with a person's daily activities, and the ability to take care of oneself, maintain relationships, engage in work activities, and to support oneself. A diagnosis also requires that the symptoms have occurred on a daily basis for at least two weeks.

TREATMENT — The goals of the treatment of depression include: Treating the symptoms Addressing family, environment, and social issues that may play a role in depression Enabling the depressed person to understand what brought about depression and what changes are necessary to resolve symptoms and prevent a relapse

Many people are reluctant to accept a diagnosis of depression and to pursue treatment. Patients may worry about the social stigma of depression, and may be embarrassed to discuss the need for treatment with family or friends. In addition, some patients may not believe that physical problems such as aches and pains, fatigue, and difficulty sleeping are caused by depression. It is important to understand that early and successful treatment of depression shortens the duration of illness, reduces the likelihood of persistent symptoms, and reduces the likelihood of a relapse.

For severe depression, treatment is usually initiated when depression is diagnosed. For mild or moderate depression, a clinician may first ask a person to keep a diary of their symptoms for several weeks.

The treatment of depression usually entails psychotherapy (counseling), drug therapy, or some combination of these therapies. In many cases, depression can be treated by a primary care provider; however, in cases of severe depression or depression that doesn't respond well to treatment, depression is usually treated by a psychiatric specialist (a social worker, psychologist, or psychiatrist).

Psychotherapy (counseling) — Psychotherapy helps alleviate symptoms in about 50 percent of people with major depression [3]. In some people, this therapy may be as effective or more effective than drug therapy. There are several different types of psychotherapy, including cognitive therapy, behavioral therapy, and interpersonal therapy.

Psychotherapy can be provided by any healthcare professional who has appropriate training in psychotherapy, including licensed psychologists, psychiatrists, clinical social workers, and clinical nurse specialists. The initial therapy sessions often focus on a better understanding of depression and may entail simple "homework activities" to begin to address the factors that may be contributing to depression. Although psychotherapy can lessen depression within several weeks, the maximal effectiveness of this therapy may not be apparent for 8 to 10 weeks.

Drug therapy — Therapy with antidepressant drugs helps reestablish the normal balance of neurochemicals in the brain. Several different classes of antidepressants effectively relieve the symptoms of depression. About half of all people with major depression have at least a 50 percent improvement in their symptoms when treated with antidepressants [4].

Time required for a response — Some people respond to drug therapy after about two weeks, but for most, the effects of antidepressants do not become noticeable for four to six weeks. Your clinician may recommend switching to another drug or may recommend treatment by a psychiatric specialist if a drug is still ineffective after 8 to 12 weeks at the maximum dose.

Duration — In most cases, antidepressant drugs should be taken for at least six to nine months. In people who experience relapses when exposed to certain events (such as stress or loss), drug therapy should be continued until these events are addressed. Some people require long-term therapy (see "Maintenance drug therapy" below).

Antidepressants and pregnancy — Women who are taking antidepressants and considering pregnancy should talk with their healthcare provider about the risks and benefits of drug therapy during pregnancy. Most antidepressants are safe for the mother and baby when taken during pregnancy.

However, paroxetine (Paxil®) has been associated with an increased risk of birth defects in babies whose mothers took the drug during the first trimester. In addition, newborns whose mothers took paroxetine or fluoxetine (Prozac®) during the third trimester have an increased risk of temporary behavior changes. These behavior changes can include tremors or slightly increased breathing rate, but rarely include more serious problems. Behavior changes usually disappear one to two weeks after birth.

There have been no reports of long-term developmental or behavioral problems in children who were exposed to antidepressants during their mother's pregnancy.

Choice of antidepressants — Many different classes of antidepressants are effective for relieving depression [5]. Thus, the choice among antidepressants depends upon other factors, including the presence of other medical conditions, the possibility of drug interactions, and the potential side effects.

It is important to discuss the expected benefits and possible side effects of antidepressants before starting treatment. It is also important to follow the guidelines for taking these drugs and to avoid combining antidepressant drugs unless you are instructed to do so. Selective serotonin reuptake inhibitors — The selective serotonin reuptake inhibitors (SSRIs) increase brain levels of the neurochemical serotonin. Low levels of serotonin have been implicated as one cause of depression. Drugs in this class include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®).

Compared with most other antidepressants, the SSRIs have fewer side effects. These side effects may include jitteriness, restlessness, agitation, headache, diarrhea and nausea, and insomnia. Sexual side effects (loss of sexual desire, diminished arousal, and difficulty having an orgasm) may also occur with prolonged use of the SSRIs; however, the addition of other drugs (such as bupropion [Wellbutrin®] or buspirone [BuSpar®]) to therapy can often relieve these sexual side effects. Bupropion — Bupropion (Wellbutrin®) alters levels of several neurochemicals in the brain but does not appear to have any direct effect on levels of serotonin. Bupropion has a mild stimulant action and may be especially effective in people with depression who have symptoms of fatigue and poor concentration.

Bupropion has few side effects, but it has been associated with seizures in people with eating disorders; it is not recommended for people who have bulimia or anorexia. The drug carries a small risk of seizures in other people. Other side effects of bupropion may include mild anxiety or insomnia and appetite suppression with weight loss. Unlike other antidepressants, bupropion does not have sexual side effects. It is sometimes used at low doses to help counter the sexual side effects of other antidepressants. Serotonin norepinephrine reuptake inhibitors — The serotonin norepinephrine reuptake inhibitors venlafaxine (Effexor®) and duloxetine (Cymbalta®) alter levels of several different neurochemicals in the brain. For unknown reasons, these drugs may be especially effective in people who have a poor response to other antidepressants. Duloxetine may be of benefit in persons with depression as well as significant physical pain from medical (eg, arthritis) or orthopaedic (eg, spinal disc disease) sources, although there have not been studies comparing duloxetine to other antidepressants for this purpose.

Common side effects include nausea, dizziness, insomnia, sedation, and constipation. Rarely, these drugs also cause increased sweating. People taking venlafaxine should have regular blood pressure checks since it may cause blood pressure to rise. Tricyclic antidepressants — The tricyclic antidepressants alter levels of several different neurochemicals in the brain. Drugs in this class include imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®).

Because of the numerous side effects associated with these drugs and the development of the SSRIs and other newer antidepressants, the tricyclic antidepressants are less commonly used as first-line antidepressant therapy. The side effects of tricyclic antidepressants may include dry mouth, blurred vision, constipation, nausea, difficulty urinating, drowsiness, weight gain, sexual problems, and rapid heart beat. In older adults, the side effects may include memory impairment, confusion, and hallucinations. Some people with heart diseases may not be able to take tricyclic antidepressants. Nevertheless, many patients use these drugs safely, and their antidepressant activity equals that of antidepressants from other classes. Monoamine oxidase (MAO) inhibitors — The monoamine oxidase (MAO) inhibitors were the first drugs used to treat depression. These drugs block an enzyme that breaks down neurochemicals. Drugs in this class include tranylcypromine (Parnate®) and phenelzine (Nardil®).

The MAO inhibitors are usually not a first choice for the treatment of depression, but they may be especially effective for the treatment of atypical depression and depression that does not respond to other drugs. Side effects of MAO inhibitors may include dizziness, dry mouth, gastrointestinal upset, difficulty urinating, headache, unpredictable muscle contractions, and afternoon fatigue.

People who take MAO inhibitors must avoid foods and beverages that contain tyramine. These include fermented cheeses; imported beer; Chianti and some other wines; champagne; soy sauces; avocados; bananas; overripe or spoiled food; and any fermented, smoked, or aged fish or meat. People who accidentally consume tyramine while taking MAO inhibitors may experience severe hypertension (high blood pressure). Trazodone — The specific actions of trazodone (Desyrel®) in the brain are uncertain, but this drug appears to alter levels of serotonin. Because trazodone may not be as effective as other antidepressant drugs and because of its potential side effects, this drug is usually not a first choice for the treatment of depression.

The most common side effect of trazodone is sedation; other side effects may include lightheadedness upon standing and nausea. The rare but potentially serious side effects of trazodone may include irregular heart beat and priapism (a persistent erection that requires medical treatment). Mirtazapine — Mirtazapine (Remeron®) is one of the newest antidepressants. This drug alters levels of several neurochemicals in the brain, including levels of serotonin. Mirtazapine has antianxiety and sedative effects and may be especially effective in people with depression who have symptoms of anxiety and insomnia.

The side effects of mirtazapine include sedation, which is actually more common at lower drug doses. Other side effects include increased appetite, weight gain, and dry mouth. Mirtazapine is less likely than other antidepressants to have sexual side effects. Rarely, the use of mirtazapine may cause a fall in the number of white blood cells and changes in liver function.

Minimizing side effects — It is important to tell your doctor if you experience side effects while taking antidepressant drugs. Your clinician may recommend one of several different measures that can minimize or eliminate these side effects: Starting at low doses and very gradually increasing the dose Taking other drugs to counter the side effects Using lower doses of the drugs Taking the drugs at a different time of the day Switching to a different drug in the same class or to a different class of drugs

It is particularly important to consult with your clinician if you decide to stop taking antidepressants. It commonly takes several weeks for a person to adjust after discontinuing antidepressants, and doctors often recommend a gradual tapering of these drugs to prevent any serious withdrawal effects.

Maintenance drug therapy — Maintenance drug therapy (long-term drug therapy) may be appropriate for people who are at risk for a relapse of depression. One study found that 37 percent of people who were treated for depression experienced a relapse within 12 months of stopping antidepressant therapy [6].

It is impossible to predict for certain whether a person will have a relapse, but two factors have been associated with a greater likelihood of relapse: A persistence of low-level depressive symptoms seven months after starting antidepressant therapy A history of two or more episodes of major depression or chronic depressive symptoms for two years

Clinicians may recommend maintenance therapy for people who have had one or more relapses of depression.

Therapy with other drugs — In some people, depression may be accompanied by other psychiatric conditions, such as panic attacks or mania. Clinicians may therefore recommend combined therapy with antidepressants and drugs such as antipsychotics, antianxiety drugs, mood-stabilizing drugs, or anticonvulsants.

Drug therapy versus psychotherapy — It is generally accepted that patients with severe depression require drug therapy, with or without additional psychotherapy. Mild or moderate depression can probably be treated with either drug therapy or psychotherapy. There are no clear predictors of which therapy may be a better choice for any given individual. Some people, especially people who have severe depression or a history of recurrent depression, may experience the greatest relief of depression when treated with both drug therapy and psychotherapy.

Treatment of other medical conditions — Depression often occurs in people who have other medical conditions, including stroke, diabetes, dementia, cancer, hypothyroidism, chronic fatigue syndrome, fibromyalgia, lupus, heart disease, Sjögren's syndrome, seizure disorders, and anxiety and panic disorders. Depression can also be associated with the use of certain drugs, such as corticosteroids.

In many cases, a cause-and-effect relationship between the medical condition or the drug and depression has not been proven. However, treatment of a medical condition or discontinuation of certain drugs often resolves depression.

Other treatment options — Several other treatment options may alleviate depression in some people.

St. John's wort — St. John's wort (Hypericum perforatum) appears to alter levels of several neurochemicals in the brain. Studies suggest that for the treatment of mild to moderate depression, St. John's wort is more effective than a placebo and as effective as tricyclic antidepressants, with fewer side effects [7]. However, the long-term effectiveness of St. John's wort is unknown.

St. John's wort is not approved by the United States Food and Drug Administration for the treatment of depression. Because the composition of St. John's wort products varies widely, some products may be less effective than others for relieving depression. The products that are most likely to be effective are those that are standardized at 0.3 percent hypericin. The dose in most studies is 300 mg three times per day, although doses as low as 250 mg twice per day may be effective.

The side effects of St. John's wort may include gastrointestinal symptoms, dizziness or confusion, sedation or tiredness, and dry mouth. Rarely, some people who take St. John's wort may notice that their skin becomes extremely sensitive to sunlight. The long-term safety of St. John's wort is unknown.

It is important to tell your clinician if you use St. John's wort. This herb can reduce the effectiveness of drugs used to treat a variety of other medical conditions, including oral contraceptives. Of particular concern are interactions with medications used to treat HIV and cancer. In general, patients on chemotherapy or antiviral therapy for HIV should not take St. John's wort. Furthermore, St. John's wort should not be used in combination with other antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs).

Studies suggest that pregnant or breast-feeding women should not take St. John's wort, and some evidence has raised concerns that the herb may lower fertility. St. John's wort is inappropriate for people with severe depression who are at risk for suicide.

A good source for updated information about St. John's wort can be found at the National Center for Complementary and Alternative Medicine, a branch of the National Institutes of Health (www.nccam.nih.gov/health/stjohnswort/).

Electroconvulsive therapy (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with depression who also have delusions (powerful, irrational beliefs) and for people who have severe depression despite maximal drug therapy. ECT can be used in pregnant women or in persons who cannot tolerate antidepressant medications, and is especially useful in persons who need a rapid-onset antidepressant treatment. (See "Medical consultation for electroconvulsive therapy").

Patients who undergo ECT are given general anesthesia and require careful monitoring. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of depression and has very few side effects. Most people who undergo ECT find it a helpful treatment for their depression.

Repetitive transcranial magnetic stimulation (rTMS) — During repetitive transcranial magnetic stimulation (rTMS), a powerful magnetic field is used to stimulate the brain. This therapy does not require anesthesia or cause any confusion or memory loss. The effectiveness of rTMS for the treatment of depression is still being studied.

Exercise — Exercise can improve depressive symptoms, although the effects occur more slowly than seen with antidepressant drugs. One study found that the depression-relieving benefit of exercise was equal to that of a selective serotonin reuptake inhibitor (SSRI) after 16 weeks [8].

Light therapy — Light therapy can very effectively relieve the depression of seasonal affective disorder (SAD). The usual dose is 10,000 lux, beginning with one 10 to 15 minute session per day, gradually increasing to 30 to 45 minutes per day depending upon response. It may take four to six weeks to see a response, although some patients improve within days. Therapy is continued until sufficient daily light exposure is available through other sources, typically from springtime sun.

Preventing suicide — Suicide is a tragic and preventable consequence of severe depression. If a clinician suspects that a person is depressed, he or she will often ask about suicidal thoughts. It is absolutely imperative to tell your clinician if you have thoughts about harming yourself or ending your life. A person who is likely to attempt suicide is given emergency treatment, including hospitalization and intensive therapy to relieve the depression that prompts suicidal thoughts.

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 Mental Health

(www.nimh.nih.gov)
American Psychiatric Association

(www.psych.org)
American Psychological Association

(www.apa.org)
American Academy of Child and Adolescent Psychiatry

(www.aacap.org)
Depression and Related Affective Disorders Association

(www.drada.org)
Depression and Bipolar Support Alliance (DBSA)

(www.DBSAlliance.org)
National Foundation For Depressive Illness

(www.depression.org)
National Mental Health Association

(www.nmha.org)
National Alliance for the Mentally Ill

(www.nami.org)



Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Kroenke, K, Jackson, JL, Chamberlin, J. Depressive and anxiety disorders in patients presenting with physical complaints: Clinical predictors and outcomes. Am J Med 1997; 103:339.
2. Zisook, S, Shuchter, SR. Depression through the first year after the death of a spouse. Am J Psychiatry 1991; 148:1346.
3. Depression Guideline Panel. Depression in Primary Care: Treatment of Major Depression: Clinical Practice Guideline. US Dept of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. AHCPR publication 93-0551, Rockville, MD 1993.
4. Trivedi, MH, Smith, H, Rush, AJ. Efficacy of antidepressants in primary care: A meta-analysis. Primary Care Psychiatry. In press.
5. Snow, V, Lascher, S, Mottur-Pilson, C. Pharmacologic treatment of acute major depression and dysthymia. Ann Intern Med 2000; 132:738.
6. Keller, MB, Koesis, JH, Thase, ME, et al. Maintenance phase efficacy of sertraline for chronic depression: A randomized controlled trial. JAMA 1998; 280:1665.
7. Woelk, H for the Remotiv/Imipramine Study Group. Comparison of St. John's wort and imipramine for treating depression: Randomised controlled trial. BMJ 2000; 321:536.
8. Blumenthal, JA, Babyak, MA, Moore, KA, et al. Effects of exercise training on older patients with major depression. Arch Intern Med 1999; 159:2349.

Bipolar disorder

INTRODUCTION — Bipolar disorder causes a person to experience periods of mania (feeling excessively elated, impulsive, irritable, or irrational) or hypomania (a milder form of mania), and may also cause a person to experience periods of major depression (feeling excessively sad).
Bipolar disorder can lead to significant illness and even death by suicide if untreated or treated incorrectly. A number of effective treatment options are available.

CAUSE — Research has helped clarify the complex biologic basis of bipolar disorder, although the exact cause is still uncertain. Studies suggest that it results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions.

People with a family history of bipolar disorder are at increased risk of developing the condition. This is thought to be the result of changes in genes, which are passed down from parents to children. Results of gene research indicate that there are probably multiple genes affected in persons with bipolar disorder.

SYMPTOMS

Mania — Mania causes a person to feel abnormally and persistently elated, irritable, hyperactive, impulsive, and irrational. These feelings last at least one week, and may be severe enough to require hospitalization. The mania of bipolar disorder is not caused by other medical illnesses or drug abuse. Other symptoms may include: Feelings of superiority and grandiosity Decreased need for sleep, restlessness Talking excessively Racing thoughts Short attention span Inappropriate laughing or joking Inappropriate spending sprees or sexual activity

Mania often causes a person to have difficulty maintaining relationships with friends and family, and can interfere with work or other responsibilities. During a manic episode, a person's moods can change rapidly from euphoria to depression or irritability.

Hypomania — Hypomania is less severe than mania, but causes a significant change in mood that is abnormal for the patient. Hypomania lasts for at least four days, but is usually briefer than manic episodes. Hypomania does not seriously impair a person's ability to function, and some people actually function better during a hypomanic episode. Hypomania does not require hospitalization, but is generally treated with medications because it may lead to a manic or depressive episode.

Depression — People with major depression experience significant sadness and difficulty functioning. They are typically depressed most of the day and may have little or no interest in any activity. Other symptoms may include one or more of the following: Significant weight loss or gain Changes in sleep patterns, including insomnia or excessive sleeping Change in activity level (including sluggishness, reduced activity, or agitation) Fatigue or loss of energy Feelings of worthlessness or guilt Difficulty concentrating and making decisions Recurring thoughts of death or suicide

To be considered major depression, a patient must have at least five symptoms on a daily or nearly daily basis for at least two weeks. In addition, symptoms must not be caused solely by a medical condition, drug abuse, medications, or the loss of a loved one. (See "Patient information: Depression in adults").

Bipolar disorder — Bipolar disorder usually presents in one of two ways: Bipolar I disorder causes at least one manic episode, often with episodes of depression Bipolar II disorder causes at least one hypomanic episode and one or more episodes of major depression.

Bipolar I disorder affects men and women equally; bipolar II disorder is more common in women. Most people develop the first symptoms of biplar disorder between 15 and 30 years of age. Newly diagnosed mania is uncommon in children and in adults over the age of 65.

People with bipolar disorder typically have cycles of relapse (when depression and/or mania occur) and remissions (when symptoms improve or resolve), often in an alternating pattern. Ninety percent of individuals who have one manic episode have another within five years. Ninety percent of individuals with bipolar disorder must be hospitalized in a psychiatric facility at least once, and two-thirds have two or more hospitalizations in their lifetime. Patients with bipolar II disorder are much more likely to have symptoms of depression than hypomania or mixed symptoms.

Alcohol, drugs, and suicide in bipolar disorder — Alcohol and drug abuse occur in more than 60 percent of people with bipolar disorder. The risk of suicide also is higher in people with bipolar disorder than in people with other psychiatric illnesses (including depression).

Suicide is often the result of feeling hopeless, and is more likely in patients with severe symptoms who must be hospitalized for treatment. Family members or friends of a person with bipolar disorder should consider any mention of suicide a serious threat, and should immediately contact a healthcare provider.

DIAGNOSIS — There is no one blood or imaging test that can determine if a person has bipolar disorder. The diagnosis is based upon a comprehensive medical and psychologic history and physical examination. Bipolar disorder can be confused with a number of other medical and psychiatric conditions. Laboratory testing may be performed to rule out other diagnoses.

TREATMENT OF MANIA — Treatment during an episode of mania focuses on managing symptoms and ensuring the patient's safety. In the early phase of mania (called the acute phase), a patient may be psychotic or display such poor judgment that they are at risk of injuring themselves or others. Hospitalization may be necessary until symptoms are controlled. Treatment of mania continues until symptoms completely resolve and the patient is able to function, although many patients are maintained on medications indefinitely to prevent a recurrence of mania symptoms.

Medications are the primary treatment for mania, and a number of medications are available. It is not usually possible to know which medication will be the most effective and cause the fewest side effects, and it may be necessary to try several medications before finding the best one. A person who responds well to one medication is likely to respond well to that treatment during future episodes.

Mood stabilizers — Mood stabilizing medications, such as lithium carbonate, lamotrigine, valproate, and carbamazepine, are often used in the treatment of mania or hypomania. Medications used for treatment of mania (and depression) are thought to cause changes in chemicals in the brain that affect mood. All of these medications are similarly effective, and the choice is often made based upon a patient's previous history, side effects, and any underlying medical illnesses.

Lithium — Lithium has been used for many years for the treatment of mania. It is usually taken two to three times per day. Common side effects include frequent urination, tremor, loose stools, and weight gain. Longer term complications include the potential for kidney or thyroid dysfunction (hypothyroidism).

Blood testing to measure the lithium level and kidney and thyroid function is usually done every 6 to 12 months once the lithium dose has been stabilized. Lithium can cause serious illness if an overdose is taken or if abnormal kidney function prevents the body from eliminating the drug. This can occur if the patient becomes severely dehydrated or uses medications such as nonsteroidal antiinflammatory drugs (eg, aspirin, ibuprofen, naproxen sodium) or an ACE inhibitor (used to treat high blood pressure).

While taking lithium, patients should talk to their healthcare provider before using any over the counter medications. Patients should give a complete list of prescription and nonprescription medications to their provider at every visit.

Valproate — Valproate is a medication occasionally used for patients with seizures, although it is also effective in stabilizing the mood of patients with mania. It may be used instead of or in combination with lithium. Common side effects include weight gain, nausea, vomiting, hair loss, easy bruising, and tremor. Liver failure and low platelet count (a type of blood cell) have rarely been associated with valproate use. Blood testing to monitor liver function and platelet count are usually done to monitor for these complications.

Carbamezapine — Carbamepazine was originally developed for prevention of seizures, but is also now used for treatment of bipolar disorder. It is usually taken twice per day. The most common side effects include nausea, vomiting, diarrhea, low sodium level, rash, itching, low white blood cell count, and fluid retention. Blood testing to monitor the carbamazepine level, liver function, and blood counts is recommended every 6 to 12 months.

Lamotrigine — Lamotrigine was also developed for seizure disorders, but may be particularly effective for depression in bipolar disorder. Routine blood tests are not needed for monitoring. Significant interactions with other medications can occur, and patients should be sure that all healthcare providers have an updated list of both prescription and nonprescription medication. An infrequent but serious and potentially life threatening rash (called Stevens-Johnson syndrome) can occur early in treatment.

Antipsychotics — Antipsychotic medications may be used alone or in combination with a mood stabilizer in patients with acute mania. Older antipsychotic medications (eg, haloperidol (Haldol®)) can cause bothersome involuntary movements (eg, tongue thrusting, tremors, restlessness). Atypical antipsychotics such as olanzapine (Zyprexa®), risperidone (Risperdal®), and quetiapine (Seroquel®) have a smaller risk of these side effects, but are more likely to cause weight gain, glucose intolerance, diabetes mellitus, and hyperlipidemia. Clozapine (Clozaril®) may be particularly effective in patients who do not respond to other mood stabilizers or antipsychotics, but it is associated with the potential for a dangerous decrease in the number of white blood cells. The newer atypical antipsychotics ziprasidone (Geodon®) and aripiprazole (Abilify®) appear to be as effective as other atypical antipsychotics, but without the risk of weight gain and diabetes. There is not as much experience with these medications, and there may be long-term risks or complications that are unknown.

TREATMENT OF DEPRESSION

Medications — During the initial phase of bipolar depression, an antidepressant medication is usually the best option for treatment. However, antidepressants may cause manic episodes, and are generally used only in the initial phase of bipolar depression in combination with a mood stabilizer. There are several types of antidepressants, each of which works slightly differently. Selective serotonin reuptake inhibitors (eg, fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®)) Bupropion (Wellbutrin®) Monoamine oxidase inhibitors (tranylcypromine (Parnate®) and phenelzine (Nardil®).

Tricyclic antidepressants (eg, imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®)) are more likely to cause mania than the medications mentioned above, and as a result are rarely used in patients with bipolar disorder.

ELECTROCONVULSIVE THERAPY (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with severe, life-threatening depression or mania that has not responded to medication.

ECT can be used in pregnant women and in those who cannot tolerate antidepressant or mood stabilizing medications, and is especially useful for those who need a treatment that begins working rapidly.

Patients who undergo ECT are given general anesthesia (medication is given to induce sleep and prevent pain). The heart and breathing rate, oxygen levels, and blood pressure are carefully monitored before, during, and after treatment is given. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of symptoms and has few side effects.

MAINTENANCE THERAPY

Medications — Once the acute symptoms of mania or depression are resolved, treatment focuses on preventing their recurrence and maintaining remission. At least one year of medication is recommended for all people who have suffered a manic episode; lifetime treatment with a mood stabilizer is often recommended for patients who have had three or more manic episodes.

Psychotherapy (counseling) — Although medications are the treatment of choice for bipolar disorder, counseling and talk therapy have an important role in treatment, particularly once an acute episode has passed. Treatment may include individual counseling as well as education, marital and family therapy, and treatment of substance abuse. Therapy may help patients to stick with their medication regimen, thereby decreasing the risk of relapse and the need for hospitalization.

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 Mental Health

(www.nimh.nih.gov/)
Depression and Bipolar Support Alliance (DBSA)

(www.DBSAlliance.org)
National Mental Health Association

(www.nmha.org)
National Alliance for the Mentally Ill

(www.nami.org/)


[1-5]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Keck, PE Jr, McElroy, SL. Outcome in the pharmacologic treatment of bipolar disorder. J Clin Psychopharmacol 1996; 16:15S.
2. Keck, PE Jr, McElroy, SL, Arnold, LM. Bipolar disorder. Med Clin North Am 2001; 85:645.
3. Gijsman, HJ, Geddes, JR, Rendell, JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161:1537.
4. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
5. Müller-Oerlinghausen, B, Berghöfer, A, Bauer, M. Bipolar disorder. Lancet 2002; 359:241.

Tuesday, October 16, 2007

Preventing complications in diabetes mellitus

INTRODUCTION — Diabetes mellitus is a chronic condition that can lead to complications over time. These complications include: Coronary heart disease, which can lead to a heart attack Cerebrovascular disease, which can lead to stroke Retinopathy (disease of the eye), which can lead to blindness Nephropathy (disease of the kidney), which can lead to kidney failure and the need for dialysis Neuropathy (disease of the nerves), which can lead to, among other things, ulceration of the foot requiring amputation

Many of these complications produce no symptoms in the early stages, and most can be prevented or minimized with a combination of regular medical care and blood glucose monitoring.

CONTROLLING BLOOD SUGAR — The long-term complications of diabetes result from the effects of hyperglycemia (elevated blood glucose levels) on blood vessels. Two important studies, the Diabetes Control and Complications Trial (DCCT) in patients with type 1 diabetes and the United Kingdom Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes, found that patients with lower blood glucose values had fewer complications than those with higher values.

Thus, keeping blood sugars close to normal can help prevent the long-term complications of diabetes mellitus. However, there are some risks associated with tight control, particularly an increased risk of hypoglycemia (low blood sugar).

Monitoring blood sugar levels — Monitoring blood sugars with finger sticks at home can indicate how well diabetes is controlled and serves as a guide to adjusting therapy. (See "Patient information: Self-blood glucose monitoring"). For most patients, a target for fasting blood glucose and for blood glucose levels before each meal is 80-120 mg/dl (4.4 to 6.6 mmol/L); however, these targets may need to be individualized for a patient by their doctor or health care team.

A blood test called A1C is also used to monitor blood sugar control; the result provides an average of blood glucose levels during the previous one to three months. An A1C of 7 percent or less is recommended; this corresponds to an average blood glucose of 150 mg/dL (8.3 mmol/L, show figure 1). The target may be somewhat higher in people who are older or who have other conditions that increase the risks associated with hypoglycemia. Patients who are unable to reach this goal can be reassured that even small decreases in A1C lowers the risk of diabetes-related complications to some degree.

The combination of A1C and fingerstick blood sugars provides information about the average blood sugar as well as daily fluctuations in blood sugar.

Type 1 diabetes — Blood sugar control in type 1 diabetes requires some form of insulin, which can be given with insulin injections, an insulin pump, or a combination of inhaled insulin and insulin injections. Most healthcare providers recommend intensive insulin therapy, which requires frequent injections, inhaled insulin, or use of an insulin pump and blood glucose monitoring. (See "Patient information: Diabetes type 1: Insulin treatment").

Intensive insulin therapy increases the risk of low blood glucose, is more expensive than traditional insulin therapy, and requires that patients monitor their blood glucose levels, dietary intake and activities; the severity of diabetic complications or hypoglycemia may limit this form of therapy in some patients with type 1 diabetes. Patients can experience weight gain with intensive insulin therapy; regular exercise and monitoring dietary intake can prevent weight gain. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").

Type 2 diabetes — Blood glucose control in type 2 diabetes may be possible with lifestyle changes alone or in combination with oral medications. Insulin is necessary in some cases in early treatment; many patients who do not initially require insulin may do so over time as their ability to manufacture insulin decreases. Generally the insulin regimen for type 2 requires fewer injections and less intensive monitoring than for type 1, although intensive insulin therapy may be recommended for some patients (See "Patient information: Diabetes type 2: Insulin treatment").

EYE COMPLICATIONS — Regular eye examinations are essential for detecting eye complications (called retinopathy) at an early stage, when they can be monitored and treated to preserve vision. This examination should be performed by a doctor who specializes in the eyes (called an ophthalmologist or optometrist). An eye exam should include dilating the pupils (with medicated eye drops) in order to completely visualize the retina. Unless the pupils are medicated, they contract in response to light, making it impossible to view the entire retina.

In some patients with retinopathy, photographs of the retina will be taken to monitor and better visualize the changes. The risk of diabetic retinopathy varies with the type and duration of diabetes and with other life events. Thus, the screening guidelines differ from one person to another.

Type 1 diabetes — People with type 1 diabetes should have an eye examination by an ophthalmologist or optometrist beginning five years after they are diagnosed with diabetes, although screening is usually not necessary before puberty. Patients who have difficulty with their vision or who require glasses or contacts may need to be seen sooner. The frequency of subsequent examinations will depend upon the results of the initial exam. Doctors usually recommend eye exams every one to two years after the initial examination.

Type 2 diabetes — People with type 2 diabetes should have an eye examination by an ophthalmologist or optometrist when they are first diagnosed with diabetes. The frequency of subsequent exams will depend upon the results of the initial examination. Doctors usually recommend eye exams every one to two years after the initial examination.

FOOT CARE — Diabetes can decrease the blood supply to the foot and damage the nerves that carry sensation. These changes put the feet at risk for potentially serious complications such as foot ulcers. Foot complications are very common among people with diabetes, and may be unnoticed until the condition is severe. (See "Patient information: Foot care in diabetes").

Self exam — Patients with diabetes should examine their feet for changes every day. It is important to examine all parts of the feet, especially the area between the toes. Patients should look for broken skin, ulcers, blisters, areas of increased warmth or redness, or changes in callus formation; a healthcare provider should be notified if any of these changes are found.

Patients should include a self-examination in their daily bathing or dressing routine. It may be necessary to use a mirror to see the bottoms of the feet clearly. Patients who are unable to reach their feet or see them completely, even with the help of a mirror, should have someone else (such as a spouse or other family member) assist with the examination.

Clinical exam — During a routine medical visit, the clinician will check the blood flow and sensation in the feet. In people with type 1 diabetes, annual foot examinations should begin five years after diagnosis. In people with type 2 diabetes, annual foot exams should begin at the time of diagnosis.

During a foot examination, the clinician will look for changes such as ulcers, cold feet, thin skin, bluish skin color, and skin breaks associated with athlete's foot. The clinician will also test the sensation in the feet to determine if it is normal or diminished. Patients with decreased sensation are at risk for foot injuries that are unnoticed due to lack of pain.

KIDNEY COMPLICATIONS — Diabetes can alter the normal function of the kidneys. A urine test which measures the amount of protein (albumin) in the urine can alert a healthcare provider that diabetes is affecting the kidney's filtering action. Microscopic amounts of albumin in the urine (microalbuminuria) can be an early indicator of diabetes-related kidney complications (called nephropathy). The amount of albumin in the urine can also help the provider determine if nephropathy is worsening. (See "Patient information: Protein in the urine (proteinuria)").

Urine screening tests should begin in people with type 1 diabetes about five years after diagnosis, and in people with type 2 diabetes at the time of diagnosis. If the test shows that there is protein in the urine, tight blood glucose and lipid control are recommended; a medication may be recommended if albuminuria does not improve.

A blood pressure medication (an ACE inhibitor or angiotension receptor blocker [ARB]) is generally recommended for patients with albuminuria that does not improve, even if blood pressures are normal. Patients with elevated blood pressures and albuminuria are also treated with an ACE inhibitor or ARB. These medications decrease the amount of protein in the urine and can prevent or slow the progression of diabetes-related kidney disease.

HYPERTENSION AND RELATED COMPLICATIONS — Many people with diabetes have hypertension (high blood pressure). Although high blood pressure produces few symptoms, it has two negative effects: it stresses the cardiovascular system and increases the progression of diabetic complications of the kidney and eye. A healthcare provider can diagnose high blood pressure by measuring blood pressure on a regular basis. (See "Patient information: High blood pressure overview").

A blood pressure reading below 130/80 is an ideal goal for most people with diabetes who do not have kidney complications; a lower blood pressure goal (<120/75) may be recommended for people with diabetes who have kidney complications.

If a patient is diagnosed with prehypertension (>120/80), the healthcare provider may recommend weight loss, exercise, decreasing the amount of salt in the diet, quitting smoking, and decreasing alcohol intake. These measures can sometimes reduce blood pressure to normal. (See "Patient information: High blood pressure, diet and weight").

If these measures are not effective or the blood pressure must be lowered quickly, the provider will likely recommend one of several high blood pressure medications. The provider can discuss the pros and cons of each medication and the goals of treatment (See "Patient information: High blood pressure treatment").

HEART COMPLICATIONS — In addition to lowering blood glucose levels, a number of other measures are important to reduce the risk of cardiac disease. Quit smoking Manage high blood pressure with lifestyle modifications and/or medication(s) Patients should have a fasting lipid blood test to measure cholesterol and triglycerides, and modify their diets. some patients may need medication to lower their LDL ("bad cholesterol") or trigylcerides, if they are high.

If medication is needed, a statin drug should be included whenever possible. The statin drugs have been shown to decrease the future risk of heart attacks, strokes, and death in people with diabetes who are over age 40, even when cholesterol levels are normal. The American Diabetes Association recommends that patients with diabetes have a low density lipoprotein (LDL) cholesterol level less than 100 mg/dL. Some studies suggest lowering LDL to 70 to 80 mg/dL. (See "Patient information: High cholesterol and lipids (hyperlipidemia)"). Aspirin (81 to 162 mg per day) is recommended for all persons with diabetes over the age of 40 years. (See "Patient information: Aspirin and heart disease").

PREGNANCY AND DIABETES — Control of diabetes and its potential complications is especially important in women planning to become pregnant, as well as in those who already are pregnant. Controlling blood glucose levels before and during pregnancy decreases the risk of a number of complications in both the mother and the baby. A separate topic review is available on this subject. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes").

Pregnancy can cause a worsening of diabetic retinopathy. Thus, women with type 1 or 2 diabetes who become pregnant should have an eye examination by an ophthalmologist or optometrist during the first trimester (three months) of their pregnancy. The frequency of subsequent eye exams during pregnancy will depend upon the results of the initial examination. In most cases, doctors recommend eye exams every three months until delivery.

These guidelines do not apply to women who have gestational diabetes -- a form of diabetes that develops during pregnancy and usually resolves after delivery. These women are not at risk for diabetic retinopathy.

THE IMPORTANCE OF REGULAR MEDICAL CARE — Regular medical care is critical to long-term health for people with diabetes, particularly when it comes to preventing, detecting, and slowing the progression of complications. A healthcare provider can recommend a regular schedule for visits, screening, and monitoring tests based upon a patient's type of diabetes (1 or 2), the duration of the disease, the presence of any complications, and the presence of other underlying medical problems.

In addition to diabetes care, patients also need to be sure they have regular screening for other health problems. For women, this may includes a cervical cancer screening, mammogram and clinical breast exam, and bone density testing. For men, prostate cancer screening is recommended after age 40. For both men and women, colon cancer screening is recommended after age 50. (See "Patient information: Screening for cervical cancer" and see "Patient information: Screening for breast cancer" and see "Patient information: Osteoporosis causes; diagnosis; and screening"). and see "Patient information: Prostate cancer screening" and see "Patient information: Screening for colon cancer").

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)
The Hormone Foundation

(www.hormone.org/public/diabetes.cfm, available in English and Spanish)


[1-6]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. 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.
2. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995; 75:894.
3. Abraira, C, Colwell, JA, Nuttall, FQ, et al. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VACSDM): Results of a feasibility trial. Diabetes Care 1995; 18:1113.
4. Nathan, DM, Cleary, PA, Backlund, JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353:2643.
5. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003; 290:2159.
6. Gray, A, Raikou, M, McGuire, A, et al. Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group. BMJ 2000; 320:1373.

Lifestyle modifications in type 2 diabetes

INTRODUCTION — Diabetes mellitus is a chronic condition, but people with diabetes can lead a full life while keeping their diabetes under control. Lifestyle modifications (changes in day-to-day habits) are an essential component of any diabetes management plan.

Lifestyle modifications can be a very effective way to keep diabetes in control. Improved blood glucose control can slow the progression of long-term complications. Multiple small changes can lead to improvements in diabetes control, including a decreased need for medication.

Diabetes requires a lifelong management plan, and persons with diabetes have a central role in this plan. Lifestyle modifications are an opportunity for diabetics to take charge of their health. Therefore, it is important to learn as much as possible about diabetes and to take an active role in making decisions about health care and treatment.

DIETARY CHANGES — Healthcare providers may recommend specific dietary changes for people with diabetes, depending upon the patient's therapy goals. Dietary changes can help with weight loss, improve blood glucose control, and lower blood cholesterol levels and blood pressure.

Calories — Lifestyle changes that promote weight loss are the primary lifestyle treatment for people with type 2 diabetes who are overweight. Improving caloric balance (eating fewer calories than are used by the body) should be consider the primary goal of lifestyle modification.

Weight loss can improve blood glucose control by decreasing insulin resistance and partially restoring the normal insulin-producing function of the pancreas. Weight loss can also lower blood pressure; high blood pressure and obesity are both risk factors in the development of cardiovascular disease. Weight gain can be a problem in patients who take insulin stimulators (like sulfonylureas, or meglitinides), thiazolidinediones (like pioglitazone and rosiglitazone) or who take insulin.

A sensible and sustainable diet, which may include reducing the number of calories eaten each day, allows for gradual weight loss over time. A healthcare provider or nutritionist can discuss an ideal weight goal with help to plan a safe and effective overall weight-loss program. While reducing calories and increasing activity are beneficial to anyone who is overweight, a focus on carbohydrate counting may also be useful for patient using insulin stimulators (like sulfonylureas and meglitinides) and insulin.

Carbohydrate counting — It is possible to adjust an insulin dose based upon the amount of carbohydrates eaten. The number of carbohydrates can be determined using nutrition labels or carbohydrate calculators (show figure 1). The dose of insulin needed based on carbohydrates eaten varies from one patient to another, and can be determined with the help of a healthcare provider (show table 1).

Post-meal blood glucose management — Blood glucose levels can rise sharply after meals. Increasing the amount of soluble fiber in the meal may slow and/or lessen this rise, and may decrease the dose of insulin needed. Soluble fiber is found in fruits, vegetables, and beans. A high-fiber diet can also lower levels of low-density lipoprotein (LDL) cholesterol (sometimes called "bad" cholesterol).

Eating foods with a low glycemic index is another approach for controlling post-meal blood glucose levels. A diet of low-glycemic index foods may also decrease LDL cholesterol levels. The glycemic index of some foods is shown in the Table (show table 2).

Increasing the dose or changing the timing of very rapid or rapid-acting insulin before meals can help control post-meal glucose levels. Very rapid-acting insulin (lispro [Humalog®], aspart [Novolog®], or glulisine [Apidra®]) should be given within 15 minutes of eating, while rapid acting insulin (Regular or R) should be given 30 to 60 minutes before a meal (show table 3).

Other approaches that can help to reduce the rise in blood glucose levels after meals include the use of alpha-glucosidase inhibitors (like acarbose or miglitol) which can be taken as a pill with the first bite of a meal. These drugs slow down the rate at which starch is broken down into glucose and so delay the absorption of glucose into the blood after a meal. These drugs are effective in some people although they can cause flatulence and diarrhea as a side effect.

Two new injectable therapies (pramlintide [Symlin®], and exenatide [Byetta®]) can also decrease the rise in blood glucose after a meal. They can also increase satiety and decrease hunger which can lead to weight loss in some patients. However, both of these drugs can cause significant nausea in some patients. In addition, patients who are taking insulin will need to reduce their insulin dose if pramlintide or exenatide are added.

Dietary guidelines — The ratio of carbohydrates, protein, and fat is important to long-term health. Current recommendations are as follows: Carbohydrates: 45 to 65 percent of total calories Protein: 5 to 20 percent Fat: 25 to 30 percent (mostly monounsaturated or polyunsaturated, not saturated fat)

Clinicians may recommend different nutrient ratios for persons with other health conditions, pregnant women, and growing children.

A low carbohydrate diet has shown favorable results in short-term studies for persons trying to improve blood glucose control, cholesterol, and lose weight. Persons with type 2 diabetes may consider a low carbohydrate diet, but should work with their healthcare provider to individualize a plan.

A moderate-salt or low-salt diet is often recommended; a low-salt diet is especially useful for lowering high blood pressure.

Timing of food intake — Consistent timing of food intake is not necessary for all people with diabetes. However, people using intensive insulin treatment may find it easier to control their blood sugar levels when they eat approximately the same amount of carbohydrates at the same time each day.

Establishing healthy dietary habits — To get started with healthy eating habits, a patient may be asked to keep a food diary, discuss current eating patterns, attend a dietary class for people with diabetes, or meet with a dietitian. Eating habits should be changed slowly, making it easier to adopt new habits.

ALCOHOL USE — The recommendations for alcohol use in persons who are diabetic are similar to those for non-diabetics. On a daily basis, no more than two alcoholic beverages for men or one alcoholic beverage for women are recommended. One alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of spirits (all of which contain 15 grams of alcohol).

Alcohol can cause either low or high blood glucose, depending upon the amount of alcohol consumed, if food was eaten at the same time, and the history of prior alcohol use or abuse. Persons with diabetes who choose to drink alcohol should drink moderately.

A moderate intake of alcohol may lower blood pressure and decrease the risk of coronary artery disease and stroke. However, excessive use of alcohol can increase the risk of neurologic and liver disease and high blood pressure.

QUITTING SMOKING — Over 25 percent of people newly diagnosed with diabetes are smokers. Quitting smoking is one of the most important things a patient can do to improve their health.

Smokers with diabetes have an increased risk of the following: Death, especially from heart attacks and strokes High "bad" cholesterol levels Worsened blood glucose controlled, compared to non-smokers Neurologic complications from diabetes Kidney disease leading to dialysis Foot ulcer and amputation of toes, feet or legs caused by peripheral vascular disease

Diabetics who quit smoking can decrease their risks. Most people who smoke find it difficult to quit; assistance is available from a number of sources. Healthcare providers have access to self-help materials, and can help select a quit date, provide contact information for local support groups, and prescribe nicotine replacement treatment, if needed.

EXERCISE — Exercise is beneficial for all individuals, with or without diabetes. Even persons with longstanding diabetes or diabetic complications can benefit from exercise.

For diabetics, exercise promotes cardiovascular fitness and weight loss, lowers high blood pressure, improves lipid profiles, improves blood glucose control in some cases, and leads to an overall sense of well-being. It may even help prevent type 2 diabetes in some people.

General exercise precautions — It is important to balance enthusiasm and common sense when beginning an exercise program. These precautions encourage patients to stay safe and ensure that exercise is productive. Wear well-fitting, protective footwear (See "Patient information: Foot care in diabetes"). Drink adequate liquids before, during, and after exercise to prevent dehydration, which can upset blood glucose levels.

Diabetics who use insulin should also: Measure blood glucose before, during, and after exercise to determine their body's typical response to exercise. If the pre-exercise blood glucose reading is 250 mg/dL or higher, exercise should be postponed until the level is under control. Consider a decrease in insulin dose by about 30 percent during exercise. Choose an insulin injection site away from exercising muscles (for example, avoid the legs if running) Keeping rapidly absorbed carbohydrates on hand (glucose tablets, hard candies, or juice). Eat a snack 15 to 30 minutes before exercise, and again every 30 minutes during exercise. Eat a source of slowly absorbed carbohydrates (dried fruit, fruit jerky, granola bars, or trail mix) immediately after exercise. This will counter a post-exercise drop in blood glucose levels.

The pre-exercise examination — People with diabetes who want to start an exercise program should consult with their healthcare provider first. A pre-exercise examination, including a supervised exercise stress test, may be needed for persons over the age of 35 and those who have had diabetes for more than 10 years.

Type of exercise — Gentle aerobic exercises, which increase the heart rate for a sustained period of time, are often the best choice for diabetics. Examples of aerobic exercise include walking, cycling, swimming, or rowing. Diabetics with well-controlled blood glucose levels and no complications can usually participate in most any type of exercise.

Choose exercise that is enjoyable and can be performed comfortably, making it easier to stay motivated and stick with a program over time. People who are accustomed to a sedentary lifestyle may find it particularly challenging to start and continue with an exercise program. Talk with a healthcare provider about any barriers that stand in the way of exercise; he or she may be able to suggest solutions.

People with diabetic eye complications (proliferative retinopathy) may be advised to avoid high-impact activities and strenuous weight-lifting, which can increase blood pressure and cause bleeding in the eye. People with neurologic complications (peripheral neuropathy) are usually advised to avoid traumatic weight-bearing exercises such as running, which can lead to foot ulcers and stress fractures although this depends on the severity of the nerve damage.

Intensity — Exercise does not have to be intense to be beneficial. Persons who want to increase the intensity of exercise should do so gradually, and should stop if he or she experience worrisome symptoms, such as chest discomfort or nausea.

Duration — A reasonable exercise session consists of 10 minutes of stretching and warm-up, followed by 20 minutes of gentle aerobic exercise. Eventually, you may wish to exercise for more than 30 minutes at a time. You should increase the duration of exercise gradually.

Timing — People who take insulin should try to exercise at the same time of the day. This practice can help to maintain predictable blood glucose levels.

Frequency — Most of the benefits of exercise for people with diabetes require a regular, long-term exercise program. Patients should commit to exercising 30 minutes a day most days of the week.

MEDICATIONS AND BLOOD GLUCOSE MONITORING — The day-to-day management of blood glucose levels can be complicated. Management may require a schedule of oral medications and/or insulin, frequent blood glucose monitoring, and carefully planned meals and snacks.

However, successful management of diabetes does not have to take the enjoyment out of life. It can be difficult to establish a routine that incorporates all aspects of diabetes care, though many people find that the routine becomes second nature once established. Written schedules may help patients to remember the details of a routine until they are committed to memory. It is also important to carefully manage situations that can complicate blood glucose control, such as sick days and vacations.

People with diabetes may need to take several medications throughout the day. Medications to lower high blood pressure, lower cholesterol levels, and low-dose aspirin may be used to manage and prevent complications. Each prescription should be taken exactly as directed on a daily basis. If the medication schedule is complex, a pill organizer or written outline may be helpful in remembering to take specific medications at specific times.

ROUTINE MEDICAL CARE — Making lifestyle changes is an excellent step towards diabetes management. However, routine medical care is important for people with diabetes; this may include frequent medical appointments and screening tests. Your healthcare team will periodically reevaluate the diabetes management plan, and can work to detect health problems that do not cause symptoms in the early stages.

Finally, it is important to listen to your body and seek care if questions or problems arise. This may require calling and seeing a clinician between scheduled appointments. Even persons who have had diabetes for many years have difficulty some times, and clinicians are skilled in helping to solve problems.

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 Institue of Diabetes and Digestive and Kidney Diseases

(www.niddk.nih.gov/)
American Diabetes Association (ADA)

(800)-DIABETES (800-342-2383)
(www.diabetes.org)
The Hormone Foundation

(www.hormone.org/public/diabetes.cfm, available in English and Spanish)


[1-4]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Close, EJ, Wiles, PG, Lockton, JA, et al. The degree of day-to-day variation in food intake in diabetic patients. Diabet Med 1993; 10:514.
2. Pan, XR, Li, GW, Hu, YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT study. Diabetes Care 1997; 20:537.
3. American Diabetes Association. Nutritional Recommendations and Principles for People with Diabetes Mellitus. Diabetes Care 1994; 17:519.
4. Torjesen, PA, Birkeland, KI, Anderssen, SA, et al. Lifestyle changes may reverse development of the insulin resistance syndrome. The Oslo diet and exercise study: A randomized trial. Diabetes Care 1997; 20:26.

Hypoglycemia (low blood glucose) in diabetes

INTRODUCTION — Hypoglycemia, also known as low blood sugar, occurs when levels of glucose (sugar) in the blood are too low. Hypoglycemia is common in people with diabetes who take insulin or oral medications that cause insulin secretion. People with type 2 diabetes often use diet control or oral medications that do not cause insulin secretion; hypoglycemia does not occur in these patients.

Hypoglycemia happens when a person with diabetes does one or more of the following: Takes too much insulin (or drugs that cause insulin secretion) Does not eat enough food Exercises vigorously without eating a snack or decreasing the dose of insulin beforehand Waits too long between meals Drinks excessive alcohol, although even moderate alcohol use can increase the risk of hypoglycemia in patients with type 1 diabetes

SYMPTOMS — The symptoms of hypoglycemia vary from person to person, and can change over time. Patients who drink excessive amounts of alcohol, are tired, or who take beta-blocking medications may not notice their symptoms, or may not recognize that the symptoms are due to hypoglycemia.

During the early stages of a hypoglycemic episode, symptoms may include: Sweating Tremor Hunger Anxiety

If untreated, symptoms can become more severe, and can include: Lack of coordination Weakness Lethargy Blurred vision Bizarre behavior or personality change Confusion Unconsciousness or seizure

When possible, hypoglycemia should be confirmed by measuring the blood glucose level. (See "Patient information: Self-blood glucose monitoring"). A blood glucose below 60 mg/dL, in the presence of symptoms, indicates hypoglycemia for most patients.

Some patients with diabetes can experience hypoglycemia at slightly higher blood glucose levels. Patients whose blood glucose levels are high for long periods of time may have symptoms of low blood glucose and feel poorly when levels approach 100 mg/dL. These patients should intensify their diabetic regimen to get blood glucose levels into a range that is closer to normal. This will lower the blood glucose level at which a patient feels symptoms.

Hypoglycemia unawareness — Hypoglycemia unawareness occurs when a person does not have the early symptoms of low blood glucose. As a result, the person cannot respond in the early stages, and severe signs of hypoglycemia, such as loss of consciousness or seizures, are more likely. It is a common occurrence, especially in patients who have had type 1 diabetes for greater than five to 10 years.

Hypoglycemia and hypoglycemia unawareness occur more frequently in patients who tightly control their blood glucose levels with insulin (called intensive therapy, show figure 1). Frequent low blood glucose levels reduce the production of the hormones which produce symptoms of low blood glucose.

Hypoglycemia unawareness can also occur in patients who take medications that stimulate insulin secretion (for example Micronase® [glyburide]), especially if they are elderly or have impaired kidney or heart function who take an oral medication that stimulates insulin secretion (show figure 2).

Nocturnal hypoglycemia — Low blood glucose that occurs when a person is sleeping (nocturnal hypoglycemia) can disrupt sleep and often goes unrecognized. Nocturnal hypoglycemia is a form of hypoglycemia unawareness. Thus, a person with nocturnal hypoglycemia is less likely to have symptoms that alert them to the need for treatment. Nocturnal hypoglycemia can be difficult to diagnose, and can increase the risk of hypoglycemia unawareness in the 48 to 72 hours that follow.

PREVENTION — The best way to prevent hypoglycemia is to monitor blood glucose levels frequently and be prepared at all times to treat it promptly. The patient as well as a close friend or relative need to learn the symptoms, and patients at risk for hypoglycemia (those treated with insulin and some oral medications, show figure 2) should always carry glucose tablets, hard candy, or other sources of fast-acting carbohydrate. Glucose tablets are recommended since they have a pleasant taste, but are not likely to be eaten for reasons other than hypoglycemia. Candy can be tempting to eat, even when blood glucose levels are normal, especially for children with diabetes.

Hypoglycemia can be frightening and unpleasant, and it is common for patients who have experienced an episode of severe hypoglycemia to be fearful of future episodes. Patients who experience this fear may keep their blood glucose excessively high, which can lead to long term complications.

It may be helpful to discuss fears of hypoglycemia with a healthcare provider. In addition, patients should ask about blood glucose awareness education and training in the use of glucagon, an injectable drug that raises blood sugar levels quickly. Blood glucose awareness training can improve a patient's ability to recognize low blood glucose earlier, which may help to prevent episodes of severe hypoglycemia.

TREATMENT — While the blood glucose level should be tested as soon as possible, treatment should not be delayed if monitoring equipment (blood glucose meter, test strips, lancet) is not readily available. Treatment of hypoglycemia should be quick, especially if blood glucose levels are less than 40 mg/dL.

As soon as symptoms are noted, a patient should eat 10 to 15 grams of fast-acting carbohydrate. Examples include: Three to four glucose tablets Six to eight hard candies 1/2 cup fruit juice

This amount of food is usually enough to raise the blood glucose into a safe range without causing high blood glucose levels (called hyperglycemia). Foods that contain fat (like candy bars) or protein (cheese) should initially be avoided, since they slow down the body's ability to absorb glucose.

After 15 minutes, the blood glucose level should be measured again. It is important to wait since it takes time for the body to absorb glucose and for symptoms to resolve. If the blood glucose level is below 60 mg/dL, or if symptoms persist, another 10 to 15 grams of fast-acting carbohydrate should be eaten.

Once symptoms and blood glucose levels are under control, a snack may be needed to control blood glucose levels until the next meal. If the next meal is more than one hour away or the patient has just completed vigorous exercise, a snack including 15 grams of carbohydrate and 1 ounce of protein should be eaten. Examples of this include crackers with cheese or one-half of a sandwich with peanut butter. It is important not to eat too much, as this can raise blood glucose levels above the target level.

Glucagon — If hypoglycemia is severe, the patient may become unconscious or unable to eat. A close friend or relative should be trained to recognize severe hypoglycemia and treat it quickly. Dealing with a loved one who is pale, sweaty, acting in a bizarre way, or unconscious and convulsing can be scary. An injection of glucagon stops these symptoms quickly.

Glucagon is a hormone that raises blood glucose levels. Glucagon is available in emergency kits, which can be bought with a prescription in a pharmacy (show picture 1). Directions are included in each kit; a roommate, spouse, or parent should familiarize themselves with the injection procedure before an emergency occurs.

It is important that the glucagon kit is easy to locate, is not expired, and that the friend or relative is able to stay calm. It is important that the kit is refilled when the expiration date approaches, though administering an expired kit is unlikely to cause harm.

Procedure — Glucagon is injected subcutaneously (under the skin) of the thigh or abdomen. The injection sites and technique are similar to an insulin injection. Remove the needle protector and inject the entire content of the syringe (a clear solution) into the glucagon powder. Do not remove the plastic clip on the syringe. Remove syringe from the bottle. Swirl the mixture gently until the powder is dissolved. The solution should be clear. Do not use the solution if it is discolored. Hold the bottle upside down and withdraw the contents into the syringe (1 mg mark on syringe for adults and children over 44 pounds [20 kilograms]). Children under 44 pounds need one-half the dose, and only 1/2 the solution should be withdrawn (0.5 mg mark on syringe). Cleanse the injection site (abdomen or thigh) with an alcohol swab (show figure 3) Insert the needle into the skin (show picture 2). Press the plunger to inject the glucagon. Withdraw the needle, and replace the syringe in the storage case (do not attempt to re-cap the needle). Press lightly at the injection site. Turn the patient to his or her side. This prevents choking if the patient vomits.

Symptoms should resolve within 10 to 15 minutes, although nausea and vomiting may follow 60 to 90 minutes later. As soon as the patient is awake and able to swallow, a fast-acting carbohydrate such as glucose tablets or juice should be offered. After the patient begins to feel better, he or she should eat a snack with protein, such as crackers and cheese or a peanut butter sandwich.

If the patient is not conscious within 10 minutes, another glucagon injection should be given, if a second kit is available. Emergency help should be called immediately.

WHEN TO SEEK HELP — A family member or friend should take a patient to the hospital or call for emergency assistance (911 in many US communities) immediately if the patient: Remains confused or in an altered mental state after being treated with glucagon Is unconscious (or nearly unconscious) and glucagon is not available Continues to have low blood glucose despite eating adequate amounts of a fast-acting carbohydrate or receiving glucagon

Once in a hospital or ambulance, intravenous glucose is given to raise levels immediately.

FOLLOW UP CARE — After the blood glucose level is normal and symptoms are gone, a patient can usually resume his or her normal activities. A patient who required glucagon should speak with his or her healthcare provider. This can help to identify the cause of a severely low blood glucose level, and adjustments can be made to prevent future reactions. Patients who require emergency care may be observed for a few hours before being released. A friend or relative should drive the patient home.

Patients should be especially careful in the first 48 to 72 hours after a hypoglycemic episode, because his or her ability to recognize the symptoms of low blood glucose may be impaired. In addition, the body's ability to counteract low blood glucose levels is decreased.

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 & Digestive & Kidney Diseases

(www.niddk.nih.gov)
American Diabetes Association (ADA)

(800)-DIABETES (800-342-2383)
(www.diabetes.org)
The Endocrine Society

(www.endo-society.org)
The Hormone Foundation

(www.hormone.org/public/diabetes.cfm, available in English and Spanish)


[1-4]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Cox, DJ, Gonder-Frederick, L, Julian, DM, Clarke, W. Long-term follow-up evaluation of blood glucose awareness training. Diabetes Care 1994; 17:1.
2. Fanelli, CG, Paramore, DS, Hershey, T, et al. Impact of nocturnal hypoglycemia on hypoglycemic cognitive dysfunction in type 1 diabetes. Diabetes 1998; 47:1920.
3. Irvine, AA, Cox, D. Gonder-Frederick, L. Fear of hypoglycemia: Relationship to physical symptoms in patients with insulin-dependent diabetes. Health Psych 1992; 11:135.
4. Weinger, K, Kinsley, BT, Levy, CJ, et al. The perception of safe driving ability during hypoglycemia in patients with type 1 diabetes mellitus. Am J Med 1999; 107:246.

Diabetes type 2: Treatment

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 and cardiovascular (heart-related) complications.

This topic review will discuss the treatment of 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").

TREATMENT GOALS

Blood glucose control — The goal of treatment in type 2 diabetes is to keep blood glucose levels at normal or near-normal levels. Careful control of blood glucose levels can help prevent the long-term effects of poorly controlled blood glucose (diabetic complications of the eye, kidney, and cardiovascular system).

Blood glucose control can be 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, and the frequency of testing can change as diabetes progresses. (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 7.0 percent or less, which corresponds to an average blood glucose of 150 mg/dL (8.3 mmol/L, show figure 1). A healthcare provider can determine the A1C goal for an individual patient.

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.

Cardiovascular risk control — The most common long-term complication of type 2 diabetes is cardiovascular (heart) disease, which can cause myocardial infarction (heart attack), angina (chest pain), stroke, and even death. The risk of heart disease is estimated to be at least twice that of persons without diabetes. (See "Patient information: Preventing complications in diabetes mellitus").

However, persons with type 2 diabetes can substantially lower the risk of cardiovascular disease by quitting smoking, taking a low-dose aspirin every day, and by managing high blood pressure and hyperlipidemia (high cholesterol) with diet, exercise, and medications. (See "Patient information: High cholesterol and lipids (hyperlipidemia)" and see "Patient information: High blood pressure treatment" and see "Patient information: Smoking cessation" and see "Patient information: Aspirin and heart disease").

Persons with type 2 diabetes are also at increased risk of developing eye, kidney, and nerve complications that can result in blindness, kidney failure, foot ulcers requiring amputation, and impotence in men. These complications can occur after many years of diabetes and are related to elevated levels of blood glucose over time. Complications can be prevented or delayed by keeping blood sugar levels as close to normal as possible and by carefully controlling blood pressure. Diabetes remains the greatest cause of blindness, kidney failure, and amputations in the United States and in much of the world.

DIET — Changes in diet can improve many aspects of type 2 diabetes, including obesity, high blood pressure, and the body's ability to produce and respond to insulin. Response to dietary changes depends upon the number of calories consumed, types of foods chosen, and the amount of weight lost.

For a person who is newly diagnosed with diabetes and who is overweight or obese, losing any amount of weight can reduce or eliminate the need for medications and improve blood glucose levels.

The American Diabetes Association recommends a low fat, low calorie, high complex carbohydrate diet. A dietitian can help to determine the optimal number of calories and fat for an individual patient. (See "Patient information: Weight loss treatments").

The following are general diet recommendations: Eat a lot of vegetables and fruits, at least five servings a day. Limit starchy vegetables (eg, potatoes) but eat as many non-starchy fruits or vegetables as desired. Choose foods with whole grains rather than processed grains. Consider whole wheat bread, brown rice, or whole wheat pasta instead of white bread, white rice, or regular pasta. High fiber foods can help a person to feel fuller sooner; 15 to 30 grams of fiber are recommended daily (show table 1A-1C). Eat a limited amount of red meat, and choose lean cuts of meat that end in loin (pork loin, tenderloin, sirloin). Remove skin from chicken and turkey before eating. Include fish two to three times per week. Choose low or fat-free dairy products, such as skim milk, non-fat yogurt, and low-fat cheese. Avoid high calorie snack foods, including regular soda, fruit punch, candy, chips, cookies, cakes, and full-fat ice cream. Use liquid oils (olive, canola) instead of solid fats (butter, margarine, shortening) for cooking. Fat should be limited to less than 30 percent of a person's total daily calories. For a 1500 calorie per day diet, this would mean about 45 g or less of fat per day, which can be counted using the nutrition information labels on most food packages (show figure 2).

For patients who are not able to lose weight with diet alone, a weight loss medication may be considered. Patients with type 2 diabetes who have a BMI greater than 35 kg/m2 can also consider a surgical weight loss procedure. (See "Patient information: Weight loss treatments", section on Weight loss medications and see "Patient information: Weight loss surgery").

EXERCISE — Regular exercise can benefit people with type 2 diabetes, even if weight is not lost. Exercise improves blood glucose control because it improves the body's response to insulin. (See "Patient information: Exercise").

Exercise does not need to be vigorous and it does not need to be continuous to produce health benefits; it can be broken up into three or four ten-minute sessions per day. The recommended goal is 30 minutes of moderate-intensity exercise at least five days per week. However, exercising only one or two days per week is better than not exercising at all.

PSYCHOLOGICAL TREATMENTS — Patients with type 2 diabetes often experience significant stress related to their disease and the increased responsibilities that come with it, including blood glucose testing, dietary considerations, exercise, healthcare provider visits, the need for medication, and the potential risks of complications. It is not uncommon to become depressed as a result of this stress, and this can make taking care of oneself more difficult.

Committing to new treatments and lifestyle changes can be difficult, and it is not uncommon to feel that the benefits of treatment are not worth the effort. Having an open and honest discussion with clinicians can help patients to understand their diagnosis and the need for treatment.

Involving family and friends can help people with diabetes to manage their disease by offering reminders to take medication, test blood glucose levels, and providing a ride to appointments. Family and friends can also give encouragement and support to eat a healthy diet and stick with an exercise plan.

Working with a psychotherapist or social worker can help patients with type 2 diabetes to cope with new responsibilities and worries. A number of studies have shown that patients who have psychotherapy in addition to traditional medical care have reduced stress and improved blood glucose control compared to patients who received only traditional care [1].

MEDICATION — A number of oral medications are available for the treatment of type 2 diabetes. A table of these medications is available in table 2 (show table 2).

Metformin — Most patients who are newly diagnosed with type 2 diabetes will immediately begin a medication called metformin (Glucophage®, Gumetza®, Riomet®, Fortamet®). Metformin improves the body's response to insulin to reduce elevated blood glucose levels.

Metformin is a pill that is usually started with a dose of 500 mg with the evening meal; a second dose may be added one to two weeks later (500 mg with breakfast). The dose may be increased every one to two weeks thereafter, up to a total of 850 mg twice per day.

Common side effects of metformin include nausea, diarrhea, and gas. These are usually not severe, especially if metformin is taken along with food and the dose is increased gradually. Patients with certain types of kidney, liver, and heart disease, and those who drink alcohol excessively should not take metformin. It should not be taken within 48 hours of any test that uses iodine-based contrast dye, and it should be stopped before surgical procedures. It is not recommended for patients older than 80 years unless kidney function testing shows that the kidneys are functioning well.

When to add a second medication — For patients who initially take metformin, 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 if the A1C is elevated, especially if it is higher than 8.5 percent.

Sulfonylureas — Sulfonylureas have been used to treat type 2 diabetes for many years. They work by increasing insulin production, and can lower blood glucose levels by approximately 20 percent. However, they lose effectiveness over time. Sulfonylureas are generally used if metformin does not adequately control blood glucose levels when taken alone, but may be used first in people who have liver, kidney, or heart disease and in those who drink alcohol excessively. They should not be used by patients who are allergic to sulfa drugs.

A number of sulfonylureas are available (Diabinese®, Orinase®, Glucotrol®, Diabeta®, Micronase®, Glynase®, Amaryl®), and the choice between them depends mainly upon cost and availability; their efficacy is similar. The medication is in pill form and is taken once or twice daily.

Patients who take sulfonylureas are at risk of low blood glucose, known as hypoglycemia. This can cause sweating, shaking, hunger, and anxiety, and must be treated quickly by eating 10 to 15 grams of fast-acting carbohydrate (eg, fruit juice, hard candy, glucose tablets). Delaying treatment can cause the person to lose consciousness. A full discussion of hypoglycemia is available separately. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").

Insulin — In the past, insulin treatment was reserved for patients with type 2 diabetes who did not have adequate blood glucose control with oral medications and lifestyle changes. However, there is increasing evidence that using insulin at earlier stages may improve overall diabetes control and help to preserve the pancreas's ability to make insulin. Insulin injections may be used as a first-line treatment in some patients, or it can be added to or substituted for oral medications.

Insulin requires an injection by the patient or a family member/friend. Inhaled insulin is newly available, but its effectiveness in treating type 2 diabetes is still being evaluated.

Most patients with type 2 diabetes begin by taking one insulin injection per day, usually at 10 P.M. The dose can be slowly increased every few days, depending upon the person's first morning blood glucose level (which should be measured every morning before eating). Some patients will need additional injections throughout the day while others have a good response to only one injection per day.

Meglitinides — Meglitinides include repaglinide (Prandin®) and nateglinide (Starlix®). They work to lower blood glucose levels, similar to the sulfonylureas, and may be used in patients who are allergic to sulfa-based drugs. They are taken in pill form. These medications are not generally used as a first-line treatment because they are more expensive than sulfonylureas and are short-acting, so they must be taken with each meal.

Thiazolidinediones — This class of medications includes rosiglitazone (Avandia®) and pioglitazone (Actos®), which work to lower blood glucose levels by increasing the body's sensitivity to insulin. They are taken in pill form and usually used second-line, in combination with other medications such as metformin, a sulfonylurea, or insulin.

Common side effects of thiazolidinediones include weight gain and swelling of the feet and ankles. There is a small but serious risk of developing or worsening congestive heart failure in patients who use thiazolidinediones. Close monitoring of swelling is important to detect this condition.

Alpha-glucosidase inhibitors — These medications, which include acarbose (Precose®) and miglitol (Glyset®), work by interfering with the absorption of carbohydrates in the intestines. This results in lower blood glucose levels, though are not as effective as metformin or the sulfonylureas. They can be combined with other medications if the first medication does not lower blood glucose levels sufficiently.

The main side effects of alpha-glucosidase inhibitors are gas (flatulence), diarrhea, and abdominal pain; starting with a low dose may minimize these side effects. The medication is usually taken three times per day with the first bite of each meal.

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)
U.S. Center for Disease Control and Prevention

(www.cdc.gov/diabetes)


[1-4]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ismail, K, Winkley, K, Rabe-Hesketh, S. Systematic review and meta-analysis of randomised controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes. Lancet 2004; 363:1589.
2. 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.
3. Nathan, DM, Buse, JB, Davidson, MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006; 29:1963.
4. Norris, SL, Zhang, X, Avenell, A, et al. Long-term effectiveness of lifestyle and behavioral weight loss interventions in adults with type 2 diabetes: a meta-analysis. Am J Med 2004; 117:762.