Alzheimer's disease

INTRODUCTION — Alzheimer's disease (AD) is a form of dementia, a group of disorders characterized by a decrease in the overall level of cognitive (mental) functioning, especially memory. In addition to memory deficits, people with Alzheimer's disease may have behavioral disturbances and experience generalized physical and mental decline. This combination eventually prevents a person from functioning independently in day-to-day life.

Alzheimer's disease accounts for 60 to 80 percent of all cases of dementia among the elderly. About four million Americans have Alzheimer's disease now, and close to three million Americans are caring for relatives or friends who have it. There is striking variety in presentation and severity of symptoms and signs, often leading to underrecognition. Currently available medical treatments can be of help in controlling the mental and behavioral symptoms of the disease but leave much to be desired in many cases. Meanwhile, ongoing research has made major advances in understanding the underlying causes of this kind of dementia. This research holds great promise for developing treatments to slow down and hopefully delay the onset or even prevent Alzheimer's disease.

CAUSES — Scientists have not yet been able to determine exactly why and how Alzheimer's disease develops. Researchers have determined that the brains of patients with AD develop deposits of a protein called beta amyloid (these deposits are also known as plaques), and that people also develop disorganized masses of protein fibers within the brain cells known as neurofibrillary tangles.

In addition, Alzheimer's disease is associated with the death of nerve cells (neurons) in important parts of the brain. Currently, these changes to the brain can only be seen during autopsy after a patient's death, but researchers are working to develop ways of imaging these brain changes in living patients.

RISK FACTORS — A risk factor is not necessarily the cause of a particular condition, but merely something that helps predict it. Some risk factors can indeed cause a particular illness. As an example, we know that smoking can cause lung cancer. The relationship between other risk factors and specific diseases is more complicated, and in many cases scientists do not know if there is any causal relationship involved or not. They just know that people who have a particular risk factor are for some reason also more likely to get a particular disease.

Age — The biggest risk factor for Alzheimer's disease is age: the older you are, the more likely you are to develop Alzheimer's disease. As an example, one large study found that among people ages 65 to 69, less than 1 percent of people develop AD per year [1]. For people ages 70 to 74, the incidence was 1 percent, and for people ages 75 to 79, 2 percent. The number affected by Alzheimer's is more than 3 percent among people ages 80 to 84, and to more than 8 percent among those 85 and over.

Family history — Having a close family member with Alzheimer's disease increases the chances of developing it yourself. People with a first-degree relative, such as a parent or sibling, with Alzheimer's disease have a 10 to 30 percent chance of developing the disorder. The risk is probably higher if the family member developed Alzheimer's disease at a younger age and lower if the family member did not get Alzheimer's disease until late in life [2].

Scientists have discovered a particular gene increases a person's risk of developing Alzheimer's. But even among individuals with this gene, only about one-half develop Alzheimer's by age 90, suggesting that other factors are also involved [3]. It is possible to test for this gene in family members of patients with Alzheimer's disease, but this test is currently recommended only for people involved in a research study.

SYMPTOMS

Normal changes versus Alzheimer's — Many people worry that memory problems are caused by early Alzheimer's disease. Normal age-related changes usually cause minor difficulties in short term memory and a slowed ability to learn and process information. These changes are usually mild and do not worsen over time, nor should they interfere with a person's day-to-day functioning.

Early changes — The earliest symptoms of Alzheimer's disease are gradual and often subtle. Many patients and their families first notice difficulty remembering recent events or information. Other changes can include one or more of the following: Confusion Difficulties with language (eg, not being able to find the right words for things) Difficulty with concentration and reasoning Problems with complex tasks like paying bills or balancing a checkbook Problems with orientation or spatial ability (eg, getting lost in a familiar place)

Later changes — As Alzheimer's disease progresses, a person's ability to think clearly continues to decline, and personality and behavioral symptoms are more likely to appear. These can include: Increased anger, hostility, and/or suspicion Aggression and physical violence Hallucinations Delusions Wandering Increased number of physical accidents

The number of symptoms and speed with which symptoms progress can vary widely from one person to the next. In some people, severe dementia occurs within five years of the diagnosis; for others, the process can take more than 10 years. Most people with Alzheimer's disease do not die from the disease itself, but instead die from a secondary illness such as pneumonia, urinary tract infection, or complications of a fall.

DIAGNOSIS — There is no single medical or laboratory test that can determine if a person has Alzheimer's disease. Instead, a healthcare provider must make the diagnosis based upon information gathered from the patient and family, and upon the results of tests that measure mental functioning.

The provider will want to know about the patient's recent history: the nature of any mental changes or memory loss, behavioral changes, any medical conditions or illnesses, and any medications the patient has been taking. A complete physical check-up and blood work may be done at this time.

It is important to rule out other possible causes for a patient's mental difficulties. These can include medications or other medical conditions. As examples, both delirium and depression have symptoms similar to those of Alzheimer's disease and may occur in patients with dementia.

The provider will also need to rule out other forms of dementia before diagnosing Alzheimer's disease. These include vascular dementia (changes caused by blood vessel abnormalities), dementia caused by Parkinson's disease, dementia related to alcohol or medications, and other conditions.

To get a sense of how the patient is functioning mentally, the doctor will probably administer a brief test such as the Mini-Mental State Exam, or MMSE. This is the most widely used test to assess a person's ability to think and remember. It takes about seven minutes to complete and evaluates a range of mental functions, including being able to state today's day, month, and year to being able to remember a short list of words or write a full sentence spontaneously.

TREATMENT — Although scientists are learning more about Alzheimer's disease all the time, currently there is no cure. There are a number of medications that may help to control some of the symptoms of Alzheimer's disease. Research suggests that treatments to prevent and even cure the condition may be available in the not too distant future.

Safety issues — A major issue in managing individuals with Alzheimer's disease is safety. Because many patients do not realize that their mental functioning is impaired, they try to continue their day-to-day activities as usual. This can lead to physical danger, and caregivers must help to avoid situations that can threaten the safety of the patient or others.

Driving — Driving is often one of the first safety issues that arises. This is often difficult to face because driving represents independence for many people. Although people with Alzheimer's disease do not have more car accidents than others during the first year after diagnosis, the risk of crashes more than doubles after the first year. It is best to discuss the issue of driving early.

There may be significant resistance to stopping driving since the patient may not realize that he or she has impairments in mental functioning or reaction time. But all patients with Alzheimer's disease will eventually reach the point where driving is dangerous to themselves and others. The healthcare provider and family must work together to determine when a patient needs to stop driving.

Most states do not have specific regulations or restrictions on driving for patients with dementia, although some do provide roadside testing and other ways of evaluating an individual's ability to drive safely. Even if a person with newly diagnosed, mild Alzheimer's disease is still able to drive, the appropriateness of driving needs to be reassessed every six months, with the expectation that driving will eventually no longer be possible.

Cooking — Cooking is another area in which dementia can lead to serious safety concerns. Symptoms such as distractibility, forgetfulness, and difficulty in following directions can lead to burns, fires, or other injuries. Many providers recommend that patients be taught early how to use a microwave oven, which poses fewer dangers than stove-top cooking.

Wandering — As dementia progresses, some patients with Alzheimer's disease begin to wander. Because restlessness, distractibility, and memory problems are common, a person who wanders may easily become lost. Identification bracelets can help ensure that a lost wanderer gets home. The Alzheimer's Association provides a "safe return" program with ID tags and 24-hour assistance (www.alz.org/we_can_help_safe_return.asp).

Regular exercise may decrease the restlessness that may lead to wandering. For patients that continue to wander, alarm systems are available that alert caretakers when the wearer goes too far from home.

Falls — For all types of dementia, including Alzheimer's disease, falls eventually become a safety concern. As an example, one study in Sweden found that among people over age 75, those with cognitive impairment were twice as likely to suffer from hip fractures as those with no impairment [4]. Caregivers should assess the physical environment in the home to eliminate potential hazards such as loose electrical cords, slippery rugs, and so forth.

Aggressive behavior — One of the most difficult issues for caregivers and Alzheimer's patients is aggressive behavior. Fortunately, this behavior is not common. However, many family members are reluctant to report a patient's aggressive behavior. In some cases, the behavior becomes physically abusive as dementia progresses. In addition, some caregivers become so frustrated that they themselves begin to behave abusively.

Family members should discuss any concerns regarding aggressive behavior with a healthcare provider, and arrange for help if necessary. Medications are available to help control behavioral difficulties in patients with Alzheimer's and also to help with mental functioning (see "Treatment of behavioral symptoms" below).

Medications — Although there are no medications available that cure Alzheimer's disease, several drugs have been developed to help control symptoms of the disease. These include medications to manage memory and cognitive impairments as well as behavioral problems. In addition, research shows promise for developing treatments to modify the course of the disease and possibly delay or even prevent it.

Treatment of the memory disturbance — There are four drugs currently available for treating memory disturbances in Alzheimer's disease. All work by decreasing the release of a chemical called cholinesterase, allowing more of a chemical called acetylcholine to be active in the nervous system. People with Alzheimer's disease have declining levels of acetylcholine in the brain. Donepezil (Aricept®) is taken once a day, usually 5 mg per day for four weeks and then increased to 10 mg per day. Clinical studies have shown that donepezil can slow memory loss in some patients with mild to moderate Alzheimer's disease [5]. Side effects, including diarrhea, nausea, and vomiting, should be monitored. Rivastigmine (Exelon®) is a cholinesterase inhibitor that helps some patients with mild to moderate disease. This drug has side effects similar to those produced by donepezil, and appears to be similarly effective. It is usually started at a dose of 1.5 mg twice per day and gradually increased to 6 mg twice per day. Galantamine (Reminyl®) is used in patients with mild to moderate Alzheimer's disease to slow the loss of mental abilities and the decline in a patient's ability to perform normal daily activities.. Memantine (Namenda®) is a unique medication that works differently than cholinesterase inhibitors. It may function to protect the brain from further damage caused by AD. It has shown promise in treating persons with moderate to severe AD. Dizziness is the most common side effect, and aggression and hallucinations may worsen in some patients. It is sometimes used along with a cholinesterase inhibitor.

Typically, one of these drugs will be tried for a period of about eight weeks while the patient is monitored for side effects and response. If there is no improvement, the drug is usually stopped (with the exception of memantine, which may be continued due to the possible protective benefits). Sometimes a patient will decline after the drug is stopped; if this happens, the drug may be started again. The drugs can be taken for as long as needed in people who benefit from their use.

It is important to have realistic expectations about the potential benefits of these drugs. As mentioned, none of them cures the disease, and over time most people will continue to have a decline in function. When these drugs are effective, the hope is that this decline will be sufficiently slowed so that patients and their families will have an improved quality of life for a longer period.

Treatment of behavioral symptoms — The behavioral symptoms of Alzheimer's disease are often more troubling than the cognitive symptoms. Even in mild cases, agitation, anxiety, and irritability can occur and generally worsen as the disease advances.

Before a patient is treated for these behavioral problems, the provider must be sure that the problem is not caused by another illness or medications. If AD is determined to be the sole cause, a combination of medication and behavioral therapy may be helpful.

Problems such as wandering, hoarding or hiding objects, withdrawal, and socially inappropriate behavior often improve more with behavioral therapy than medications. Other problems, such as agitation, aggression, delusions, and hallucinations may be more responsive to medications. Because these latter behaviors are often the reason for putting an Alzheimer's patient into a nursing home, most providers try to control these problems as soon as they appear.

Delusions are common in patients with dementia, occurring in up to 30 percent of those with advanced disease. Paranoid delusions are particularly distressing to both the patients and the caregivers: these often include beliefs that someone has invaded the house, that family members have been replaced by impostors, that spouses have been unfaithful, or that personal possessions have been stolen. If these delusions are troublesome, antipsychotic medications can be prescribed to help control them.

In choosing a medication, the side effects must be considered. Some medications can worsen mental processes and cause sedation, while others may cause unacceptable side effects such as muscle tremors, tics, rigidity, etc.

The choice of medications for troublesome delusions and hallucinations is complex. Providers typically begin these drugs at the lowest effective dose to minimize side effects. Depression — Depression is a problem that sometimes occurs in people with dementia. Depression is not always present throughout the course of dementia. It can be difficult to diagnose because other behavioral changes occur that have similar symptoms. (See "Patient information: Depression in adults").

If depression is suspected in a person with Alzheimer's disease, the first step may be to try an antidepressant medication. A group of medications known as selective serotonin reuptake inhibitors, or SSRIs, are usually preferred. SSRIs include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®). These medications are often helpful, but may be needed lifelong.

Other antidepressants, such as venlafaxine, duloxetine mirtazapine, and bupropion may also be effective, but have not been well studied in people with Alzheimer's disease.

Although tricyclic antidepressants have been studied for years and in low doses generally have a good safety profile, they are no longer recommended as first line agents in the treatment of people with dementia who have with depression because they may cause increased side effects. It is not necessary to stop a tricyclic antidepressant if it is working well.

Other treatments, such as behavioral therapy may also be recommended for depression. Behavioral therapy involves changing the environment that produces the depression (eg, encouraging exercise, socialization). Behavioral changes are believed to lead to changes in thoughts and emotions. Anxiety and aggression — These problems can be caused by a number of factors, including: Confusion or misunderstanding Frightening or paranoid delusions Depression Sleep disorders Medical conditions such as difficulty urinating or severe constipation

The best treatment for these symptoms depends upon what triggers them. As an example, a person who becomes aggressive during periods of confusion might best be treated through behavioral therapy, while someone who becomes aggressive during delusions might require medication.

Studies of older antipsychotic medications (haloperidol, thioridazine, thiothixene, chlorpromazine, trifluoperazine and acetophenazine) concluded that there was no clear evidence of benefit for these agents in patients with dementia [6]. One review concluded that haloperidol may help control aggression, but not other neuropsychiatric manifestations of dementia [7].

A newer class of medications known as atypical neuroleptics (aripiprazole, olanzapine, quetiapine, and risperidone) have been the medications of choice for treating hallucinations in patients with dementia. However, use of these medications for the treatment of behavioral problems in elderly patients with dementia is associated with an increased risk of death [8].

Nonetheless, the benefit of atypical neuroleptics often still outweigh their risks when treatment of hallucinations and delusions is necessary. Because there are no other medications that are effective, some experts continue to use them cautiously, after informing the patient and family about the potential risks. Sleep problems — Patients with sleep disorders may benefit from both medication and behavior changes: for example, limiting daytime naps, increasing physical activity, avoiding evening consumption of caffeine and alcohol, as well as a sleeping medication. However, sleeping pills also will worsen confusion.

Medications typically used to ease agitation and sleeping difficulties include the antidepressant trazodone (Desyrel) and the mood stabilizer carbamazepine (Epitol, Tegretol). Benzodiazepines such as alprazolam (Xanax) and diazepam (Valium) are not generally recommended for people with Alzheimer's disease because of their side effects (sedation).

Treatments that may be effective — A number of therapies have been studied in patients with Alzheimer's disease, including some that may alter the course of the dementia, not just treat the symptoms.

Vitamin E and selegiline — Reports of the effectiveness of vitamin E (alpha-tocopherol) have appeared in the popular press and research findings suggest that vitamin E may slow the progression of Alzheimer's disease. Another substance believed to help slow the condition is the drug selegiline (Eldepryl). In a study that compared vitamin E, selegiline, and a combination of the two, the two treatments were equally effective, and no advantage was seen in the group that took both [9].

There were some problems with the methods of this study, making it difficult to know for sure if vitamin E is beneficial in preventing or slowing the progression of AD. Nevertheless, this trial was the first to show a benefit of any therapy for delaying the progression of Alzheimer's disease. Some clinicians recommend that people with Alzheimer's disease take 1000 IU of vitamin E twice daily; this has fewer side effects and is less expensive than selegiline.

There is growing concern regarding the increased risk of death related to use of vitamin E supplements. Vitamin E is appropriate only for patients with AD or at high risk of developing AD (ie, those who have more than one family member with AD) who lack significant heart disease. We do not recommend vitamin E for the routine prevention of AD or other types of dementia.

Estrogen — Estrogen has been studied as a treatment that might slow the course of Alzheimer's disease. However, the most recent and well-controlled studies have shown no beneficial effects [10-12].

Nonsteroidal antiinflammatory drugs — Research with nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and indomethacin has been inconclusive. So far, there is no evidence that these drugs can help treat Alzheimer's disease. NSAIDs should not be used for the treatment or prevention of dementia.

Ginkgo biloba — The herbal supplement ginkgo biloba has also been studied in patients with Alzheimer's disease and shown some promise in reducing mental decline [13]. The use of ginkgo is appealing since it has few side effects. However, we do not recommend the use of ginkgo because there is little evidence that it is effective and because it's production is not regulated; it is considered to be a dietary supplement, which means that the dose and ingredients can vary from pill to pill and bottle to bottle.

FUTURE TREATMENT AND PREVENTION — A number of research projects are currently underway to study how Alzheimer's develops and progresses over time. This kind of research holds considerable promise for treatment of AD symptoms, changing the course of AD, and even preventing it.

Some research is aimed at discovering more about the amyloid-beta plaques that develop in the brains of Alzheimer's patients, and how to prevent or even remove them. The protein tangles that are characteristic of Alzheimer's are another target of research, with the first goal being to figure out whether these tangles actually contribute to the disease or are a result of it, perhaps caused by the amyloid-beta plaques.

Animal research has shown that vaccines made from the amyloid-beta proteins may be able to slow the progression of brain damage in Alzheimer's and possibly even reverse it [14-16]. This kind of research will not yield results for treating humans for years, but the findings so far are promising.

The best hope may be to discover risk factors for Alzheimer's disease. Simply delaying the age of onset could significantly reduce the burden of the illness for patients, families, and other caregivers.

LIFE WITH ALZHEIMER'S — Being diagnosed with Alzheimer's disease can be overwhelming for both patients and their loved ones. However, the diagnosis does not mean that life is over.

For patients — It is important for people with early Alzheimer's disease to care for their physical and mental health. This means getting regular checkups, taking medications if needed, eating a healthy diet, exercising regularly, getting enough sleep, and avoiding activities that may be risky.

It may be helpful to talk to a counselor or social worker to discuss feelings of frustration, anger, loneliness, or depression. All of these feelings are normal, and dealing with these feelings can help a person to feel more in control of their wellbeing. Support groups are also available for patients and families to discuss these issues with other people dealing with similar problems.

Another issue to consider is how to tell family and friends about the diagnosis of Alzheimer's disease. Explaining the disease can help others to understand what to expect and how they can help, now and in the future. This can be especially helpful for children and grandchildren, who may not be familiar with the condition.

Patients may live alone in the early stages of Alzheimer's, but often need help with tasks such as housekeeping, cooking, transportation, and paying bills. If possible, ask a friend or family member for help to develop plans to deal with these and other issues as the condition progresses. In addition, patients and their loved ones should discuss preferences regarding issues that are likely to become important as AD worsens, including health insurance, where the patient will live, and the financial resources to pay for care. A number of resources are available to assist in this type of planning. (See "Where to get more information" below).

For caregivers — Alzheimer's disease is a debilitating disease that can impose an enormous burden on patients and families or other caregivers. People with Alzheimer's disease become less able to care for themselves as the disease progresses. Some tips that may help caregivers create a positive environment include the following: Make a daily plan and prepare to be flexible if needed. Focus on the process, not the end result. Try to be patient when responding to repetitive questions, behaviors, or statements. This type of behavior is common, and often is the result of feeling insecure or nervous. Use memory aids such as writing out a list of daily activities, phone numbers, and instructions for usual tasks (ie, the telephone, microwave, etc). Establish calm nighttime routines to manage behavioral problems, which are often worst at night. Leave a night light on in the patient's bedroom. Avoid major changes to the home environment. Employ safety measures in the home, such as locks on medicine cabinets, keep furniture in the same place to prevent falls, remove electrical appliances from the bathroom, install grab bars in the bathroom, and set the water heater at or below 120ºF. Help the patient perform personal care as they are willing and able. It is not necessary to bathe every day, although a healthcare provider should be notified if the patient develops sores in the mouth or genitals related to hygiene problems (eg, urinary incontinence, ill-fitting dentures). Speak slowly, present only one idea at a time, and be patient when waiting for responses. Encourage physical activity and exercise. A daily walk can help prevent physical decline and improve behavioral problems [17]. Consider respite care. Respite care can provide a needed break for family and can strengthen the family's ability to provide care in the future. This is offered in many communities in the form of in-home care or adult day care. Caregiving can be an all-consuming experience. Be sure to take time for yourself, take care of your own medical problems, and arrange for breaks when you need them.

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 Neurological Disorders and Stroke

(www.ninds.nih.gov)
National Institute of Mental Health

(www.nimh.nih.gov)
Administration on Aging (Department of Health and Human Services)

(www.aoa.dhhs.gov)
The American Geriatrics Society

(www.americangeriatrics.org)
Alzheimer's Association

(www.alz.org)
Alzheimer's Disease Education and Referral (ADEAR) Center (National Institute on Aging)

(www.nia.nih.gov/alzheimers)
Eldercare Locator (Administration on Aging)

(www.eldercare.gov)
Family Caregiver Alliance

(www.caregiver.org)



Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Hebert, LE, Scherr, PA, Beckett, LA. Age-specific incidence of Alzheimer's disease in a community population. JAMA 1995; 273:1354.
2. Silverman, JM, Smith, CJ, Marin, DB, et al. Familial patterns of risk in very late-onset Alzheimer disease. Arch Gen Psychiatry 2003; 60:190.
3. Henderson, AS, Easteal, S, Jorm, AF. Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample. Lancet 1995; 346:1387.
4. Guo, Z, Wills, P, Viitanen, M, et al. Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: A community-based prospective study. Am J Epidemiol 1998; 148:887.
5. Rogers, SL, Farlow, MR, Doody, RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group [see comments]. Neurology 1998; 50:136.
6. Sink, KM, Holden, KF, Yaffe, K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005; 293:596.
7. Lonergan, E, Luxenberg, J, Colford, J. Haloperidol for agitation in dementia. Cochrane Database Syst Rev 2002; :CD002852.
8. Lee, PE, Gill, SS, Freedman, M, et al. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004; 329:75.
9. Sano, M, Ernesto, C, Thomas, RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study [see comments]. N Engl J Med 1997; 336:1216.
10. Shumaker, SA, Legault, C, Thal, L, et al. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA 2003; 289:2651.
11. Shumaker, SA, Legault, C, Kuller, L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2947.
12. Espeland, MA, Rapp, SR, Shumaker, SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2959.
13. Le Bars, PL, Katz, MM, Berman, N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA 1997; 278:1327.
14. Schenk, D, Barbour, R, Dunn, W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse [see comments]. Nature 1999; 400:173.
15. Weiner, HL, Lemere, CA, Maron, R, et al. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease. Ann Neurol 2000; 48:567.
16. Morgan, D, Diamond, DM, Gottschall, PE, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 2000; 408:982.
17. Teri, L. Gibbons, LE, McCurry, SM., et al. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA 2003; 290:2015.

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.

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.

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.