FitSugar

Strike a Yoga Pose: Cow Face

FitSugar — Mon, 11 May 2009 03:30:00 -0700

If you're looking for a relaxing pose that will stretch your shoulders, chest, hips, and ankles, it's time to try Cow Face. Named because your knees look like a cow's closed mouth and your elbows look like ears, this pose also strengthens your core to help improve your posture.

Sanskrit Name: Gomukhasana
English Translation: Cow Face Pose

To learn how to do this pose read more.

Sit on your mat with both legs straight in front of you. Bend both knees and slide your left foot under your right thigh. Lift your bum off the floor, point through your left toes and sit down gently on your left heel. If it hurts to sit on your heel, then sit on the floor with your left heel beside your right hip.
Bring your right foot as close to your left hip as possible, so both knees are stacked. Whichever variation you're doing, the tops of your feet should be resting on the mat.
Bend your left elbow behind your back. Lift your right arm straight up above your head, then bend your right elbow and if you can, clasp your fingers together.
Gaze toward the ceiling and hold here for five deep breaths.
Take a vinyasa and then switch sides.

Strike a Yoga Pose: Cow Face

FitSugar — Mon, 06 Aug 2007 04:00:00 -0700

Sometimes it's nice to do a relaxing pose that stretches your muscles, but doesn't require a large amount of strength or energy. This pose called Cow Face is really calming, yet gives your hips and shoulders an awesome stretch.

The name is intriguing and you might be wondering why is it called Cow Face? Take a look at yourself in a mirror while doing this pose. Your crossed legs are the lips, and your bent elbows are the ears. See it now?

Sanskrit Name: Gomukhasana
English Translation: Cow Face Pose
Also Called: Cow Face

Want to see how to get into this pose? Then read more

Begin sitting on your mat with your legs out in front of you as if you were about to do a Seated Forward Bend. Now bend your left leg and sit on your heel. If this is uncomfortable, just place your left heel to the outside of your right hip.
Now bend your right knee and cross your thigh over your left thigh, bringing your right heel beside your left hip.

If you want to go further, reach your right arm straight up above your head. Then bend your left elbow, and sweep your left arm behind your back. Bend your right elbow and try to touch or clasp both hands together at the middle of your spine. If you can't reach your hands, hold opposite ends of a towel or strap.
Try to sit nice and tall, with your neck and spine straight. You can press your head back slightly against your right arm to open your shoulder even more.
Stay here for 5 or more breaths and then gently release. Shake out your arms a little and then do the other side.

Fit's Tips: If you love Cow Face pose, here's another shoulder stretch for you to try.

Source

Skin wrinkles and blemishes

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Smoking and Skin Damage

The skin of smokers ages more rapidly than the skin of non-smokers, even in areas of the body not exposed to sunlight, according to a 2007 study. Women in the study who smoked also had much lower levels of vitamin E secretions in their skin. Vitamin E may protect the skin from sun damage.
There may be an association between smoking and higher frequency of a type of acne (noninflammatory acne) in adult women, according to a European study.

Antioxidants and Your Skin

A study in the Journal of Nutrition found that a combination of antioxidants and trace elements supplementation raises the risk of skin cancer in women, but not in men.

Ultraviolet Radiation

Overall, exposure to ultraviolet radiation from sunlight (radiation referred to as UVA or UVB) accounts for about 90% of the symptoms of premature skin aging.
UVB primarily affects the outer skin layers. It is most intense when sunlight is brightest. People receive slightly over 70% of their yearly UVB dose during the summer.
UVA penetrates more deeply and efficiently. The intensity of UVA rays is less dependent on the time of day and season of the year than that of UVB rays.

Vitamin D

A report analyzing studies of vitamin D supplementation found that people who take vitamin D supplements live longer than those who do not. People who avoid sunlight are at risk for vitamin D deficiency.

Introduction

As you age, your skin undergoes progressive changes:

The cells divide more slowly, and the inner layer of skin (the dermis) starts to thin. Fat cells beneath the dermis begin to shrink. In addition, the ability of the skin to repair itself decreases with age, so wounds heal more slowly. The thinning skin becomes vulnerable to injuries and damage.
The deeper layer of the skin, which provides scaffolding for the surface skin layers, loosens and unravels. Skin then loses its elasticity (ability to stretch). When pressed, it no longer springs back to its initial position. Instead, older skin sags and forms furrows.
The sweat- and oil-secreting glands atrophy (waste away), leaving the skin without a protective layer of water and fat. The skin's ability to stay moisturized then decreases, and it becomes dry and scaly.
Frown lines (those between the eyebrows) and crow's feet (lines that spread from the corners of the eyes) appear to develop because of permanent small muscle contractions. Habitual facial expressions also form characteristic lines.
Gravity makes the situation worse, contributing to the formation of jowls and drooping eyelids. Eyebrows, surprisingly, move up as a person ages, possibly pulled up by forehead wrinkles.

Wrinkles can have a profound impact on self-esteem. The stigma attached to looking old is evidenced by the more than $12 billion Americans spend each year on cosmetics to hide the signs of aging. Our society places a premium on youthfulness, and age discrimination in the workplace, although illegal, has stalled many people's careers. Indeed, the emotional consequences of aging explain in large part why the cosmetics industry and plastic surgeons thrive.

The sun is the most important cause of prematurely aging skin (a process called photoaging) and skin cancers. Overall, exposure to ultraviolet radiation from sunlight (radiation referred to as UVA or UVB) accounts for about 90% of the symptoms of premature skin aging. Most of these effects occur by age 20:

Even small amounts of UV radiation trigger the processes leading to skin wrinkles.
Long-term repetitive exposure to sunlight adds up, and likely is responsible for the vast majority of unwanted consequences of aging skin, including basal cell and squamous cell cancers.
Intense exposure to sunlight in early life is an important cause of melanoma, a particularly aggressive type of skin cancer.

Initial Damaging Effects of Sunlight. Ultraviolet radiation penetrates the layers of the skin. Both UVA and UVB rays cause damage leading to wrinkles, lower immunity against infection, aging skin disorders, and cancer. They appear to damage cells in different ways, however.

UVB is the main cause of sunburns, and primarily affects the outer skin layers. UVB is most intense at midday when sunlight is brightest. People receive slightly over 70% of their yearly UVB dose during the summer. We receive only 28% during the remainder of the year. Window glass filters out UVB.
UVA penetrates more deeply and efficiently. The intensity of UVA rays is less dependent on the time of day and season of the year than that of UVB rays. For example, you receive only about half of your yearly UVA dose during the summer months, with the balance spread over the rest of the year. Window glass does NOT filter out UVA.

Both UVA and UVB rays cause damage to the body, including genetic injury, wrinkles, aging skin disorders, and skin cancers. Exactly how they cause this damage is not yet fully understood.

Processes Leading to Wrinkles. Even small amounts of UV radiation trigger the processes that can cause wrinkles:

Sunlight damages collagen fibers (the major protein that gives structure to the skin). Sunlight also causes damage to elastin, a protein in the skin that normally maintains springiness and strength of tissue beneath the skin.
In response to this sun-induced elastin accumulation, the body produces large amounts of enzymes called metalloproteinases. One study indicated that when people with light to moderate skin color are exposed to sunlight for just 5 - 15 minutes, the metalloproteinase levels in their body remain high for about a week.
The normal function of these metalloproteinases is generally positive -- to remodel the sun-injured tissue by producing and repairing collagen. This is an imperfect process, however, and some of metalloproteinases produced by sunlight actually degrade (break down) collagen. The result is an uneven formation (matrix) of disorganized collagen fibers called solar scars. Repetition of this imperfect skin rebuilding causes wrinkles.
An important event in this process is the over-production of oxidants, also called free radicals. These are unstable molecules that are normally produced by chemical processes in the body, a process called oxidation. Environmental damage, however, causes an overproduction of oxidants. Excessive amounts of oxidants damage the body's cells and even alter their genetic material. Oxidation may contribute to wrinkling by activating the specific metalloproteinases that degrade connective tissue.

In addition to sunlight, other factors may hasten the formation of wrinkles:

Cigarette Smoke. Smoking produces oxygen-free radicals, which accelerate wrinkles and aging skin disorders, and increase the risk for non-melanoma skin cancers. Studies also suggest that smoking and subsequent oxidation produce higher levels of metalloproteinases, the enzymes associated with wrinkles.

Air Pollution. Ozone, a common air pollutant, may be a particular problem for the skin. One study reported that it might deplete the amount of vitamin E in the skin. This vitamin is an important antioxidant.

Rapid Weight Loss. If weight loss occurs too rapidly, the volume of fat cells that cushion the face are also decreased before chemicals in the skin can react. This not only makes a person look gaunt, but can cause the skin to sag.

Blemishes

This report covers three types of blemishes: Liver spots, purpura, and seborrheic keratoses (or warts).

Liver spots (known as lentigos, or sun-induced or pigmented lesions) are flat brown spots on the skin. They are almost universal signs of aging. Occurring most noticeably on the hands and face, these blemishes tend to enlarge and darken over time. The extent and severity of the spots are determined by a combination of skin type, sun exposure, and age. These spots are harmless, but should be distinguished from lentigo maligna, which is an early sign of melanoma.

Liver spots or age spots are a type of skin change that are associated with aging. The increased pigmentation may be brought on by exposure to sun, or other forms of ultraviolet light, or other unknown causes.

Treating Liver Spots. Liver spots do not require treatment, although some people are distressed by their appearance. Treatments may include the following:

Trichloroacetic acid (a chemical peel).
Tretinoin (Retin A) alone or in a combination with Mequinol (Solagé). Tretinoin is related to vitamin A, and is also effective in treating wrinkles.
Gentle freezing with liquid nitrogen (cryotherapy).
Laser treatment. Specific lasers, such as the Nd:YAG, are effective in eliminating 80% of liver spots in one treatment. It may be more effective than cryotherapy and have fewer side effects.
Bleaching creams -- these are commonly available but are not as satisfactory as peels, and high concentrations can sometimes cause permanent loss of skin color.

Purpura occurs when tiny capillaries (blood vessels) break and leak blood into the skin. In older people, the condition (called senile or actinic purpura) is usually caused by fragile blood vessels. The capillaries appear as flat purplish patches. These patches are called petechiae when they are smaller than 3 mm (about a tenth of an inch). When they are greater than 3 mm, they are referred to as ecchymoses. Patients typically complain of a rash, which may appear reddish at first but gradually change color, turning brown or purple.

Treatment. Although there is no specific treatment for purpura, patients are advised to avoid trauma, including vigorous rubbing of the skin, which may be sufficient to damage the capillaries. Emollients that soften the skin may be helpful. Some doctors also recommend vitamin C, but its effectiveness is unproven.

Seborrheic keratoses, (also called seborrheic warts), are among the most common skin disorders in older adults. Their cause or causes are unknown. They usually appear on the head, neck, or trunk and can range in size from 0.2 - 3 cm (a little over an inch). They are well defined and appear to be pasted onto the skin, but their appearance can vary widely:

They can be smooth with tiny, round, pearl-like formations embedded in them.
They can be rough and warty.
They can be brown or black.

Seborrheic keratoses sometimes look like melanoma, since they can have an irregular border, but they are always benign. A dermatologist can tell the difference between them, although experts warn that melanomas may "hide" among these benign lesions and go unnoticed without close inspection. In general, seborrheic keratoses have a uniform appearance while melanomas often have a smooth surface that varies in height, color density, and shading. In some cases, keratoses may cause itching or irritation. They can be easily removed with surgery or freezing. Vitamin D3 ointment is also showing promise in clinical trials.

Risk Factors

Exposure to Sun in Childhood. It is estimated that 50 - 80% of skin damage occurs in childhood and adolescence from intermittent, intense sun exposure that causes severe sunburns. In spite of this now well-known effect, many people still believe that a tan in children signifies health. And even though many parents are concerned about sun exposure, they still rely too much on sunscreen and not enough on protective clothing.

The Elderly. Most people over 70 have at least one skin disorder. Many have three or four. Everyone experiences skin changes as they age, but a long life is not the sole determinant of aging skin. Family history, genetics, and behavioral choices all have a profound impact on the onset of aging-skin symptoms.

Of all the risk factors for aging skin, exposure to UV radiation from sunlight is by far the most serious. Indeed, the vast majority of undesirable consequences of aging skin occur in individuals who are repetitively exposed to the sun, including the following:

Outdoor workers, such as farmers, fishermen, construction workers, and lifeguards
Outdoor enthusiasts
Sunbathers
People who regularly attend tanning salons or use tanning beds (One study indicated that regular use significantly increases the risk for non-melanoma skin cancers. Fair-skinned women under age 50 may be at particular risk.)

Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.


Skin Type	Tanning and Burning History
I	Always burns, never tans, sensitive to sun exposure
II	Burns easily, tans minimally
III	Burns moderately, tans gradually to light brown
IV	Burns minimally, always tans well to moderately brown
V	Rarely burns, tans profusely to dark
VI	Never burns, deeply pigmented, least sensitive

The common belief is that women are at greater risk for wrinkles than men. Some evidence suggests, however, that given the same risk factors, men and women in the same age groups have comparable risks for skin photoaging. In a French study, the evidence of moderate-to-severe photoaging was observed in the following:

Twenty two percent of women and 17% of men ages 45 - 49
Thirty six percent of women and 38% of men by age 54
Nearly half of both men and women by age 60

Some studies report that men are more likely to develop non-melanoma skin cancers.

Heavy smokers are almost five times more likely to have wrinkled facial skin than nonsmokers, according to one study. The skin of smokers in areas of their bodies not exposed to sunlight also seems to age more rapidly, compared to non-smokers in the same age group, according to a 2007 study. In fact, heavy smokers in their 40s often have facial wrinkles more like those of nonsmokers in their 60s.

Studies of identical twins have found smokers to have thinner skin (in some cases by as much as 40%), more severe wrinkles, and more gray hair than their non-smoking twins. Even worse, cigarette smokers are more prone to skin cancers, including squamous cell carcinoma and giant basal cell carcinomas. A European study found an association between smoking and higher frequency of a particular type of acne in adult women. The study also found that women who smoked had much lower levels of vitamin E secretions in their skin. Vitamin E is an antioxidant that may help protect the skin from sun damage. [See In-Depth Report #41: Smoking.]

Prevention

The best long-term prevention for overly wrinkled skin is a healthy lifestyle.

Eat Healthy. A diet with plenty of whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil) may protect against oxidative stress in the skin. One study reported that people over age 70 years had fewer wrinkles if they ate such foods. Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries. Benefits from these foods may be due to high levels of anti-oxidants found in them.

Exercise. Daily exercise keeps blood flowing, which brings oxygen to the skin. Oxygen is an important ingredient for healthy skin.

Reduce Stress. Reducing stress and tension may have benefits on the skin.

Quit Smoking. Smoking not only increases wrinkles, but smokers have a risk for squamous cell cancers that is 50% higher than nonsmokers' risk. Smokers should quit smoking to prevent many health problems, not just unhealthy skin.

The following are some daily measures for skin protection:

Don't wash your face too often with tap water. (Once a day is enough.) It strips the skin of oil and moisture. In addition, chlorinated water, particularly at high temperatures, poses special risks for wrinkles.
Wash your face with a mild soap that contains moisturizers. Avoid alkaline soaps, especially with deodorant.
Pat the skin dry and immediately apply a water-based moisturizer.
Always apply sunscreen, even if going outdoors for short periods.
Avoid drinking alcohol within 3 hours of bedtime. Alcohol increases the risk for leaks in the capillaries, which allows more water in and causes sagging and puffiness. Capillary leakage increases when one is lying down.
Lie on the back when sleeping. This helps offset the effects of gravity.

One of the most important ways to prevent skin damage is to avoid episodes of excessive sun exposure. The following are some specific guidelines:

Use sunscreens that block out both UVA and UVB radiation. However, do not rely only on sunscreen for sun protection. Wear protective clothing and sunglasses in addition.
Avoid exposure particularly from 10 a.m. to 4 p.m., when sunlight pours down 80% of its daily UV dose.
Avoid reflective surfaces, such as water, sand, concrete, and white-painted areas. Clouds and haze are not protective and in some cases may intensify UVB rays.
Ultraviolet intensity depends on the angle of the sun, not heat or brightness. So the dangers are greater the closer to the summer-start date. For example, in the Northern Hemisphere, UV intensity in April (2 months before summer starts) is equal to that in August (2 months after summer begins).
The higher the altitude the quicker one sunburns. One study suggested, for example, that an average complexion burns in 6 minutes at an altitude of 11,000 feet at noon, compared with 25 minutes at sea level in a temperate climate.
Avoid sun lamps and tanning beds or salons. They provide mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon is as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning or promotions offering unlimited tanning.

Sunscreens. The use of sunscreens is complex, and everyone should understand how and when to use them. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.

Protective Clothing. Wearing sun-protective clothing is extremely important and protects even better than sunscreens. Special clothing is now available for blocking UV rays and is rated using SPF ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however. The following are some tips for everyone:

Adults and children should wear hats with wide brims. Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.
People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave, the more protective the garment.
Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
Everyone over age 1 should wear sunglasses that block all UVA and UVB rays.

Chemical Tanners. Some research suggests that melanin and dihydroxyacetone (DHA), the active ingredients in many self-tanning lotions, may help filter out UVA and UVB radiation and are therefore protective against sun damage More research is underway. A preliminary study funded by the National Cancer Institute found that people who received numerous daily injections of melanotan-1 (MT-1) before going in the sun or a tanning bed tanned more quickly and showed fewer signs of sun-related damage. MT-1 is a synthetic version of the hormone melanin, which helps produce the skin's natural pigment (color).

In choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:

Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. In addition, many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA. It is not known if they have the same effects.
The Food and Drug Administration approved Anthelios SX in July 2006. This new sunscreen prevents sunburn and protects against ultraviolet A and B rays. The product contains ecamsule, an ingredient not previously marketed in the United States.
Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.

Inexpensive products work as well as expensive ones with the same ingredients. Unfortunately, there are still no standards for sunscreens, and even those claiming UVA protection may offer very little. In one study, the average UVA protection from a wide range of brands was only 23%. In fact, the average protection of brands not making the claim was 37%!

Organic formulas and inorganic microfine oxides do not protect against visible light, which is a problem for people who have light-sensitive skin conditions, including actinic prurigo, porphyria, and chronic actinic dermatitis. Inorganic sunscreens that protect against visible light and are still cosmetically acceptable are now available in Europe, but not yet in the US.

Calculating the SPF. The sun protection factor (SPF) on all sunscreen labels is a ratio based on the amount of UVB (not UVA) radiation required to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.

Protection offered by sunscreens may be classified as follows:

Minimal: SPF 2 to 11.
Moderate: SPF 12 through 29.
High: 30+. (Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.)

SPF Levels by Age Group. Certain groups should have higher or lower SPFs depending on age and other factors:

Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. In fact, experts are worrying that by relying too much on sunscreen and not providing other protective measures, parents may actually be increasing their children's risk for melanoma. All young children should be well covered with clothing, sunglasses, and hats as the first line of defense against sunburn. Children should be kept out of the sun during peak sunlight periods. Sunscreens should not be used on babies younger than 6 months without consulting a doctor.
Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.
Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.

Timing and Amount of Application. You should apply sunscreen or sunblock liberally as follows:

Adults should include sunscreen with a daily skin regimen, even if going outdoors for only a short time.
Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
Apply initially 30 minutes before venturing outdoors for best results. (This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
Also reapply each time after exercise or swimming. (Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.)
Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.

Possible Hazards of Sunscreens, Sun Avoidance, or Both. When used generously and appropriately, sunscreen products and sun avoidance help reduce the severity of many aging skin disorders, including squamous cell cancers. There are certain concerns, however.

Sunscreen Use May Not Protect Against Basal Cell and Melanoma Cancers and May Even Increase the Risk. Although sunscreens help prevent squamous cell carcinomas and other skin disorders, sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.

The reasons for this possible increased risk are unclear, though some theories include the following:

Until recently, many sunscreens blocked only or mostly UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Past studies may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
People who apply sunscreens may feel safe and stay out longer during high sun-exposure hours than is safe. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
People may not put on enough sunscreen. According to a 2002 study, people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. (Of note, a 2003 study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure. However, omitting it even once resulted in significant cell injury.)

Sunscreen Use May Increase the Risk for Health Problems Related to Sunlight Deficiencies. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems, such as the following:

Vitamin D Deficiency. Vitamin D is found in only a few foods, such as fortified dairy products and fish, but it is produced in the skin in response to UVB sunlight. A medical literature review published in the journal Nutrition and Cancer reported that UVB rays may outshine dietary supplements for building the body's vitamin D reserves. Without an appropriate mix of diet and supplements, vigorous sun protection measures may increase a person's risk for developing vitamin D deficiency. Vitamin D is important for prevention of rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin. Note: vitamin D is toxic in high doses. Most doctors recommend 200 IU a day (for young adults) to 600 IU a day (above age 70). Doses up to 2,000 IU a day are considered safe. A report analyzing studies of vitamin D supplementation found that people who take vitamin D supplements live longer than those who do not. The researchers looked at 18 studies. They found that participants who received vitamin D supplements were, on average, 7% less likely to die during the study they were in, compared with those receiving "sugar pills."
Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
Depression. Many people suffer from SAD (seasonal affective disorder), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.

The bottom line is that some sunlight is important and even necessary for a healthful and high-quality life. Adults may benefit from daily moderate tanning (20 - 30 maximum minutes of exposure during lower-risk hours) over several days to slowly build up pigment in the skin.

Treatment

An increasing number of dermatology patients are looking for a way to improve the appearance of their skin. As a result, more and more products have become available to treat skin wrinkles and blemishes. From vitamins and supplements to exfoliants and chemical peels -- the options can be overwhelming. In some cases, more than one approach may be needed.

Antioxidants are substances that hunt oxygen-free radicals, the unstable particles that can damage cells. Free radicals may also cause sun damage and even skin cancers. Exposure to sunlight depletes antioxidants in the skin, and therefore they must be replaced.

Antioxidant ointments, creams, and lotions ("topical products") may help reduce the risk of wrinkles and protect against sun damage. Unlike sunscreens, they build up in the skin and are not washed away, so the protection may last. Selenium, coenzyme Q10 (CoQ10), and alpha-lipoic acid are types of antioxidants that come in topical form. Many are proving to be very beneficial for the skin.

Vitamin A. Vitamin A is important for skin health. UV radiation produces vitamin A deficiencies in the skin. Topical products containing natural forms of vitamin A (retinol, retinaldehyde) or vitamin A-related products called retinoids (tretinoin, tazarotene) may help repair skin damage due to sunburn and natural aging.

Tretinoin (Retin-A). Tretinoin (known commercially as Retin-A) is the only topical agent approved for treating photoaging and is available in prescription form (Avita, Renova, Differin). The June 2004 issue of Dermatology Surgery reported that tretinoin (0.25% concentration) was an effective and well-tolerated treatment for photodamaged facial skin. This drug produces a rosy glow and reduces fine and large wrinkles, liver spots, and surface roughness. It also may help prevent more serious effects of ultraviolet radiation. Patients may apply tretinoin to the face, neck, chest, hands, and forearms, and should do so at least twice a week. Noticeable improvement takes 2 - 6 months. Because Retin-A increases a person's sensitivity to the sun, patients should apply just a tiny amount at bedtime, and wear sunblock during the day. Patients should also avoid overexposure to the sun. Almost all patients experience redness, scaling, burning, and itching after 2 or 3 days that can last up to 3 months. In women who experience irritation, a daytime moisturizer or low-dose corticosteroid cream, such as 1% hydrocortisone, may help. There is some concern that overuse of high-dose tretinoin may cause excessive skin thinness over time. Studies now suggest that low concentrations (as low as .02%) of tretinoin can produce significant improvements in wrinkles and skin color, with less irritation than the higher doses.
Retinol. Retinol, a natural form of vitamin A, could not, until recently, be used in skin products because it was unstable and easily broken down by UV radiation. Stable preparations are now sold over the counter. In the right concentrations, retinol may be as effective as tretinoin, and studies indicate that it has fewer side effects. An animal study suggests that adding antioxidant creams (such as those containing vitamins C or E) may offer added protection against degradation of retinol, but not tretinoin. The Food and Drug Administration warns that over-the-counter retinol skin products are unregulated. The amount of active ingredients is unknown, and some preparations, in fact, may contain almost no retinol.
Tazarotene. Tazarotene (Tazorac, Zorac, Avage) is a retinoid used for acne and psoriasis. It has now been approved for treating wrinkles, skin discoloration, and blemishes due to photoaging. One short-term study suggested that it may be as effective as tretinoin and even slightly better at high doses. At such high doses, however, it can cause very severe irritation. Redness and peeling may be reduced by administering tretinoin first to get the skin acclimated. A randomized study of 562 patients with facial photodamage found that a daily application of tazarotene 0.1% cream resulted in a minimum 1 grade improvement in fine and coarse wrinkling, uneven skin color, pore size, skin roughness, and overall photodamage. More research is needed to determine if it produces any long-lasting significant benefits.

Warning: Pregnant women and those who may become pregnant should avoid any vitamin A derivative (a product related to vitamin A). For example, oral tretinoin causes birth defects, and women should avoid even topical Retin-A when pregnant or trying to conceive.

Vitamin C. Vitamin C, or ascorbic acid, is a very potent antioxidant. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts of vitamin C reduced skin swelling and protected immune factors from sunlight. It may even promote collagen production. Vitamin C by itself is unstable, but products that solve the delivery problem are now available (such as Cellex-C, Avon's Anew Formula C Treatment Capsules, Physician Elite, and others). More research is needed.

Antioxidants Under Investigation for Skin Care. Other antioxidants are also being investigated for their value in skin protection. Most available brands, however, contain very low concentrations of these antioxidants. In addition, they are also not well absorbed and have a short-term effect. New delivery techniques, however, may prove to offset some of these problems.

Vitamin E. Studies suggest that topical vitamin E, particularly alpha tocopherol cream (a form of vitamin E), decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also reported reductions in UV-induced skin cancer with its use.
Both green and black tea may provide some protection against skin cancers and photoaging. There is also some evidence that pomegranate and soy extracts may help rejuvenate aging skin.
Aloe, ginger, grape seed extract, and coral extracts contain antioxidants and are promoted as being healthy for the skin, although evidence of their effects on wrinkles is weak.

A small study found that taking vitamin C and E supplements by mouth -- at the same time -- may help reduce sunburn, although it doesn't work as well as sunscreen. Taking the vitamins separately did not have any effect. Vitamin C and E are also antioxidants.

One of the basic methods for improving skin and eliminating small wrinkles is exfoliation (also called resurfacing), which is the removal of the top layer of skin to allow regrowth of new skin. Methods for doing this run from simple scrubs to special creams to intensive peeling treatments, including laser resurfacing. People with darker skin are at particularly higher risk for scarring or discoloration with the more powerful exfoliation methods.

Abrasive Scrubs. Scrub gently with a mildly abrasive material and a soap that contains salicylic acid to remove old skin so that new skin can grow. The motion should be perpendicular to the wrinkles. Use textured material or cleansing grains with microbeads. Organic materials, such as loofahs or sea sponges, may harbor bacteria. Avoid cleansing grains that contain pulverized walnut shells and apricot seeds, which can scratch skin on a microscopic level. Cleansing grains with microbeads don't have sharp edges and remove skin without cutting it. Exfoliation using scrubs, however, can worsen certain conditions, such as acne, sensitive skin, or broken blood vessels.

Topical Alpha Hydroxy Acid and Similar Substances. Alpha hydroxy acids (AHA) ease the shedding of dead skin cells and may even stimulate the production of collagen and elastin. Their natural forms are:

Lactic acid (milk)
Glycolic acid (sugar cane)
Malic acid (found in apples and pears)
Citric acid (oranges and lemons)
Tartaric acids (grapes)

Most alpha hydroxy acid products contain glycolic acid. Skin care products are also made from polyhydroxy acids (PHAs) and beta hydroxy acids (BHAs). Research suggests that PHA products may cause less skin irritation than AHA or BHA products.

Acid concentrations in over-the-counter AHA preparations are 2 - 10%. One clinical study suggested that 8% concentrations showed modest skin improvement Some examples include Avon's Anew Intensive Treatment (8% glycolic), Pond's Age Defying Complex (8%), Elizabeth Arden's Alpha-Ceramid Intensive Skin Treatment (3 - 7.5%), and BioMedic's home product (10%). Prescription strength creams contain at least 12% glycolic acid, and glycolic acid peels of 30 - 70% concentration may be administered in a doctor's office at weekly or monthly intervals.

Response to AHA varies, and the treatment is not without risk, particularly in high-concentration products. Side effects from over-the-counter creams, prescription products, and professional AHA peels can include burns, itching, pain, and possibly scarring. Studies also suggest that AHA may increase susceptibility to sun damage, even at concentrations as low as 4%. Such effects can persist up to a week after a person stops using the product. Experts advise that people purchase products with AHA concentrations of 10% or less. Chemical peels of up to 60% are available without prescription on the Internet. Such concentrations are not recommended, except under a doctor's supervision. If any adverse effects occur, stop using the product immediately. Always avoid sunlight or use proper sun protection when using these products.

Copper Peptides. Certain copper-containing compounds may protect skin and help repair it. Note: copper is a toxic metal. When using products containing copper, buy only those that contain peptides (small protein fragments) that bind to copper. Most studies have been conducted on the copper peptide glycyl-l-histidyl-l-lysine:copper (II) or GHK-Cu. It is currently used in a number of products (such as CP Serum, Neutrogena's Visibly Firm, ProCyte's Neova).

Furfuryladenine. Furfuryladenine (Kinetin, Kinerase) is a naturally occurring growth hormone found in plant and animal DNA. It has antioxidant and anti-aging properties. Some small laboratory studies suggest that furfuryladenine may delay the onset and decrease the effects of aging on skin. However, there are no well-conducted human studies to support this suggestion.

Vitamin K. Microsponge-based vitamin K is said to clear bruises spider veins, and other small blood vessel damage. Vitamin K is important for blood clotting.

Moisturizers help prevent dryness, bruising, and tearing. They have no effect on wrinkles by themselves. Moisturizers should be applied while the skin is still damp. These products retain skin moisture in various ways:

Occlusives, such as petroleum jelly, prevent water from evaporating.
Humectants, including glycerin, act by pulling water up to the surface of the skin from deep tissues. People with oily skin generally should use the humectant type.
More powerful compounds, such as monolaurin (Glylorin), contain mixtures of fatty molecules (lipids), which may help restore the skin's natural barriers against moisture loss and damage.

Most moisturizers contain combinations of these compounds. They usually have other ingredients as well, such as alpha hydroxy acids, sunscreens, collagen, and keratin. Collagen and keratin leave a protein film and temporarily stretch the skin. They range widely in price, and a major consumer organization found little difference in general between the more and less expensive products.

The skin under the eyes is very thin and does not produce as much of the protective oils that keep skin soft and supple. Manufacturers market their under-eye gels as being able to reduce puffiness and dark circles. The creams typically work in one of two ways:

By temporarily constricting blood vessels to prevent the build-up of fluids
By firming the skin with an invisible film

Never rub the creams under the eyes, as this may cause more wrinkles to form. Instead, apply these products with a light tapping motion to stimulate the skin.

Cosmetics, if properly applied, can be surprisingly effective in camouflaging the signs of aging skin, including wrinkles and age spots. Moreover, they offer additional benefits by retarding water loss and providing a physical barrier to UV radiation. However, as women age, less is more.

Here are some suggestions for older women:

Moisturizers. Apply moisturizers before foundation. If reddish discoloration is extensive or the skin is sallow, tinted moisturizers may be helpful and can be worn alone or under foundation.

Foundations. Caking on make-up will cause cracks at the wrinkle lines and only increase the appearance of aging. Try to cover large areas of the face with a moderate-coverage foundation that has a matte or semi-matte finish. Facial powder reflects light and thus minimizes wrinkles, but people with dry skin should avoid it.

Correcting Color. When blemishes are especially prominent, applying color correctors under the foundation can be very effective:

Green neutralizers mask red lesions.
Yellow will camouflage dark circles and bruises.
Mauve (a purplish-pink color) helps neutralize sallow skin or yellowish blemishes.
A white, pearled base helps to minimize wrinkles.

Blushes. Blushes and color washes can help conceal the spidery network of dilated capillaries on the nose and cheeks. Powder blushes are preferred because they blend easily on top of foundation.

Eyes. Powder eye shadows applied on top of a moisturizer are better than cream-based shadows. Light-colored shadow, applied along the upper eyelid crease and above the iris (the colored part of the eye) is best for offsetting the appearance of deep-set eyes. You should then apply a slightly deeper shade of the same color to the lower part of the eyelid, and draw it out to the corner.

Lips. A lip-setting cream or facial foundation should be applied before lipstick to help prevent it from bleeding into surrounding wrinkles. Try using a stiff bristle brush instead of a lip pencil. The brush will help keep the lipstick on and prevent bleeding. (Some women use the pencil itself for the full lip, which gives color but appears natural.) Some make-up artists recommend cream lipsticks instead of matte.

The Food and Drug Administration (FDA) does not regulate herbal remedies and dietary supplements. In other words, the manufacturers and distributors of such products do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been numerous reported cases of serious and even deadly side effects from herbal products.

Overexposure to sunlight can damage skin. The following natural remedies may cause extra sensitivity to light (photosensitivity):

St. John's wort (Hypericum perforatum) is a popular herbal remedy for depression. People who are sensitive to light should not use it. A case report suggests that St. John's wort may cause skin reactions in patients who have laser treatment.
Kava (Piper methysticum) is an herb used to calm nerves and reduce stress. In addition to photosensitivity, it can cause liver damage.
Yohimbe (Pausinystalia yohimbe) is used to treat erectile dysfunction. Both the herb and the pharmaceutical drug (yohimbine) can cause sensitivity to light.
Essential oils in many botanical aromatherapy products can trigger photosensitivity. Avoid citrus oils (grapefruit, lemon, lime, and orange) as well as bergamot, cumin, ginger, and angelica root oils.

Resurfacing Treatments

There are many choices for skin resurfacing (also called exfoliation), and the patient must consider several different factors that affect the choice. Resurfacing can achieve the following:

Removal of abnormal tissue and rough skin
Stimulation of new skin growth
Stimulation of collagen and elastin production

In addition to determining the skill of the surgeon and the safety of the procedure, the patient must discuss the desired depth of the resurfacing and the capability of each procedure to reach this depth safely. All resurfacing procedures require a healing period afterward, during which the skin is red and sensitive. The deeper the procedure, the higher the risk for complications, including delayed healing, infection, loss of pigment (skin color), and scarring.

If you make the decision to pursue intensive treatments, consider the following factors, among others, and discuss them with your dermatologist or plastic surgeon:

The ability of the procedure to safely reduce wrinkles
The ease and safety record of the procedure
The skill of the doctor
The length of recovery
Possible complications
How long the benefits will last

A person's age also helps determine the procedure:

For people in their 30s, a simple chemical peel is sufficient.
After age 40, people may benefit from collagen or fat implants.
At age 50 and over, plastic surgeons recommend laser resurfacing and customized treatments for individual needs.

In older individuals, combination procedures may be beneficial. Some examples include the following:

Laser surgery may be used for deep lines (such as those around the mouth) and chemical peels used over the rest of the face.
For enhancing the eye by correcting droopy eyelids, bags, and a "sinking" brow, combinations of eyelift (blepharoplasty), Botox, and laser resurfacing may be used.

Chemical peels, also known as chemosurgery, help restore wrinkled, lightly scarred, or blemished facial skin. Much like chemical paint strippers, chemical peels strip off the top layers of skin, and new, younger-looking skin grows back. The procedure is very effective for the upper lip but cannot be performed around the eyes. Partial peels are often done in conjunction with a face-lift. Combinations of the topical antioxidants, such as tretinoin and vitamin C, along with a chemical peel, may be particularly effective.

The Procedure.

A dermatologist applies chemicals to the skin. They include trichloroacetic acid, high concentrations of alpha hydroxy or beta hydroxy acids, or combinations of all three.
In some cases, tretinoin or alpha hydroxy is applied 4 - 6 weeks before, and starting one day after, the peel. Such treatments can enhance the effects of a peel and reduce the risk of discoloration in people at risk for this complication. Tretinoin is being tested as a chemical peel.
A crust or scab generally forms within 24 hours after surgery. You can remove this scab by gently cleansing with soap and water.
The skin takes 6 - 7 days to heal.
After the scab disappears, the visible skin is deep red but gradually lightens as it regenerates.

Complications. Complications include white heads, cold sores, infection, scarring, numbness, and permanent discoloration, particularly in people with darker skin. Refinement of chemical peel techniques are now permitting doctors to reach deeper skin, improvements which make it easier to apply peels to non-facial skin and to individuals with darker skin.

Dermabrasion affects deeper layers of skin than chemical peels, and may be useful for removing disfiguring marks, such as deep acne scars or deep wrinkles. As with chemical peels, it is effective for wrinkles on the upper lip and chin, and cannot be used around the eyes. Some doctors prefer dermabrasion to lasers for skin surfacing of people with darker skin colors.

Standard Dermabrasion. Standard dermabrasion uses a rotating brush that removes the top layers of a person's skin. As with chemical peels, dermabrasion selectively strips away the upper layers of skin, leaving the underlying skin layers exposed. Similar to chemical peels, after the procedure, the treated skin oozes and forms a scab, a reaction that looks and feels uncomfortable, but only temporary. Postoperative care is similar for both procedures.

Microdermabrasion. A gentler variation called microdermabrasion uses very tiny crystals to polish the skin and a vacuum technique to remove them. It has largely replaced the older dermabrasion, and, in fact, was the fourth most common non-surgical cosmetic procedure performed in 2005, with over a million done. Results are similar to light chemical peels. Patients can have this procedure done on their lunch hour and return to work. Only mild redness occurs after treatment, although for best results five or six repetitive treatments are needed every 1 - 2 weeks. To date, overall patient satisfaction has been very high.

Lasers are currently the most effective exfoliation tools for eliminating wrinkles. Their unique advantages over other resurfacing methods are their ability to tighten the skin. A successful procedure can make patients look 10 - 20 years younger, and the results can last up to 10 years.

The procedure is most beneficial for the following areas:

It is best around the mouth and eyes. Recent evidence suggests CO₂ lasers may be even better than dermabrasion for the upper lip.
It is slightly less beneficial for the area around the nose.

Used alone, current laser therapy does not eliminate crow's feet, broken blood vessels, or dark circles under the eye. The evidence of the effects of lasers on acne scars is incomplete.

Standard laser dermabrasion is too harsh for thinner skin layers, such as on the neck. Newer and gentler laser techniques, however, stimulate collagen without removing skin layers, and may prove to be useful for necklines.

The Laser Resurfacing Procedure. In general the procedure works in the following way:

Laser pulses penetrate the skin quickly, vaporizing water and surface skin without damaging the deeper layers, allowing new top skin to grow.
In addition, the laser delivers enough heat to shorten collagen fibers, restoring some elasticity to the skin.

Choice of Lasers. The lasers used depend on skin type and severity of the condition. Some of the more common laser types are:

The carbon dioxide (CO₂) laser. This is the most powerful laser treatment and is used for deep wrinkles and skin imperfections. People who have had silicone injections should not have CO₂ procedures, which can burn and scar the skin over the implanted area.
The erbium: YAG (Er:YAG). This laser is gentler than the CO₂ laser, and is effective for mild wrinkles and for providing a smooth skin texture. It has a shorter recovery time. Some experts have even found the YAG laser as effective in removing deep wrinkles as CO₂ when used to sufficient depth. A variable pulse YAG laser can shift between pulses that destroy skin tissue to those that heat the skin. This process effectively resurfaces the skin with fewer side effects than CO₂ laser therapy.
Pulsed dye laser. Pulsed dye laser uses yellow light, which is easily absorbed by hemoglobin, the molecule that gives blood its red color. Pulsed dye laser treatments are used to treat skin blemishes that are due to blood vessel abnormalities, such as port-wine stains.

A gentle laser procedure called non-ablative laser resurfacing (NLite), also called photorejuvenation, is now approved for the treatment of all facial wrinkles. The procedure uses light energy to gently stimulate new collagen, and possibly elastin production, without removing the skin tissue itself. Its effects are less pronounced than those of other laser procedures. However, because it does not injure the external layers of skin, it can be used on delicate skin areas, such as the neck and around the eyes. It also causes very little irritation afterward.

Some surgeons are using combination techniques that employ more than one laser technology in one session, to achieve different effects. For example, one combination technique uses CO₂, YAG, pulsed-dye laser, and one other laser technology to both improve wrinkles and clear under-eye dark circles and acne scarring. Pretreatment with botulinum (Botox) injections before laser resurfacing significantly improved the treatment of crow's feet in one study.

Post-Procedure Recovery. The procedure itself is relatively painless, but the redness and irritation that occur during the healing process can be severe. Non-ablative laser resurfacing does not have the same severe after-effects as other laser treatments. For 8 - 9 days, the face looks skinned and swollen, and requires continuous moisturizing. Some doctors suggest that people with very sensitive skin, who cannot tolerate the necessary medications and lubricants, should avoid laser resurfacing. Redness and sensitivity can persist for 1 - 4 months. The patient must stay out of the sun as much as possible during this time, and should always avoid sunbathing and damaging their skin again. Early research suggests that silicone dressings may reduce post-procedure pain and crusting.

Complications. Scarring and infections can occur in about 1% of procedures. The risk of complications depends on the experience of the surgeon. People with a history of herpes simplex may experience flare-ups of fever, facial pain, and flu-like symptoms for 5 or 6 days after the procedure. In addition, people with darker skin may wish to avoid the procedure, because it can cause unpredictable and dramatic lightening of the skin.

A new skin rejuvenation technology, called Plasma Skin Resurfacing, or Portrait Plasma, was introduced in February 2005. The technology uses plasma energy (heat and light energy) to rejuvenate the skin from the deeper layers outwards. While new skin regenerates, the outer layers of the skin act as a natural bandage. When the outer layers peel off in the week after treatment, the new skin emerges. The process prevents or minimizes the raw appearance that follows laser treatments. This system uses radio waves to "excite" nitrogen gas, resulting in the release of energy. According to the manufacturer, skin regeneration using the Portrait Plasma system is rapid, and satisfaction with the procedure appears high. Long-term follow-up studies are not available yet for this new method. In 2006, the Food and Drug Administration approved this method for the treatment of wrinkles on other areas of the body, besides the face.

Cold Ablation. Cold ablation, called coblation for short, delivers saline (salt water) to the skin, through which a cool electric current is passed. A subsequent reaction heats and vaporizes the top shallow layer of skin. The procedure is very specific and appears to minimize any damage to other areas of the skin.

Radiofrequency Resurfacing. A promising technique uses low radiowave energy to resurface the skin. Preliminary research indicates that this procedure may eventually be as effective as laser surgery in reducing severe wrinkles around the eyes and mouth, with minimal pain and a shorter recovery time. In one study, one radiofrequency treatment with only a skin anesthetic resulted in tighter facial skin for 14 out of 15 patients within 12 weeks. All but one patient returned to normal activity immediately afterward. A small clinical trial published in Dermatology Surgery found that a noninvasive radiofrequency technique called NARF safely and effectively improved drooping lower eyelids.

Intense Pulsed Light. Intense pulsed light (IPL) uses filters to deliver different wavelengths of light. Doctors use it to treat a number of photoaging skin problems, and it appears to have long-term effects. Typically, four to six treatments are performed over a four-month period. Each treatment takes 15 - 20 minutes. Unlike laser light, which uses one color wavelength (such as green or red), intense pulsed light starts with a full spectrum of light. It then allows the doctor to selectively block off specific wavelengths, depending on how shallow or deep the procedure should go. IPL machines are less expensive and safer than lasers.

Implant Procedures

Implants, also called injectable fillers, are becoming a common means of erasing wrinkles and folds. Several materials are being used for deep wrinkles, depression under the eyes, lip enhancements, and acne scars.

After being banned from the market in 1992, silicone is making a comeback in research settings as a potential permanent wrinkle eraser. Scientists are looking into a new microdroplet technique (the use of very small drops) combined with purified silicone as a way to eliminate any danger. The past problems with silicone occurred when it was mixed with a foreign substance, like mineral oil, or when it was injected in large doses.

Most implants to date, however, are not completely satisfactory. Collagen implants and biologic fillers from animal, bacterial, or human sources do not provide long-lasting benefits. Synthetic fillers are permanent but may cause an allergic reaction, which can lead to chronic problems. Such reactions are rare, but they can be painful and unattractive.

The U.S. Food and Drug Administration (FDA) approved the Juvéderm product line in June 2006. Juvéderm is an injectable treatment of moderate-to-severe facial wrinkles and folds. Juvéderm products are gels made from hyaluronic acid. They are injected into the face. Doctors report good results after a single treatment with Juvéderm, and the results last for at least 6 months.


Name and Material Used	Procedure	Specific Areas Affected	Benefits	Drawbacks
Collagen implants. Collagen is the protein that forms the structures in the body (such as skin, bones, cartilage). The implant procedure has typically used bovine (cow) collagen. A form of human collagen (CosmoDerm, CosmoPlast) has now been approved.	Injected into target wrinkles with needle and syringe. Several weeks after injection, cow collagen breaks down and is replaced by newly created human collagen.	Wrinkles around the eyes and mouth. It is used to give lips greater fullness.	Very simple with faster recovery than many other implant techniques.	Wrinkles form again, and require repeat treatments 3 - 12 months later. Rarely, severe allergic reactions occur. Should not be used by children, pregnant women, and people with a history of autoimmune disease.
Microlipoinjection. Fat tissue from the patient's own thigh or abdomen.	Injected into target wrinkles with needle and syringe.	Deep wrinkles around the nose and mouth, folds in the forehead, and wrinkles on the hands.	No allergic or immune reaction because substance is patient's own fat.	Body eventually absorbs the fat, resulting in a need for multiple injections. Some studies suggest that 70% of the fat may still be in place after at least a year.
Gore-Tex. Highly porous (full of tiny holes) and inert (not chemically active) synthetic material.	Requires some surgery. Tiny patches are inserted under the skin to fill out wrinkles. Skin cells and blood vessels pass through the porous material easily, reducing the risk of severe irritation.	Deep wrinkles.	Material does not break down.	Possible scarring from surgical procedure. Allergic reactions are rare but can occur even with chemically inactive materials.
Artecoll. Contains PMMA, or polymethylmethacrylate, an inert substance, enclosed in tiny droplets of natural collagen.	Material is injected. Body absorbs collagen. PMMA remains and stimulates new collagen growth.	Deep wrinkles.	Although part of the implant is a natural collagen implant, it does not degrade as quickly as a full collagen implant.	Repeat treatments may still be needed. Possible allergic reaction.
Hyaluronic acid. Natural (non-animal) substance acts like a molecular sponge to absorb water. The FDA approved Restylane in 2003, Captiva, Hylaform-Plus, and Hylaform in 2004, and Juvéderm in 2006.	Gel is injected under the skin.	Moderate-to-severe wrinkles.	Low risk for allergic reaction. May last longer than cow collagen.	Repeat treatments needed.
Poly-L-lactic acid. Synthetic polymer. Approved in US as Sculpta. Approved in other countries as New-Fill.	Material is injected under the skin.	Approved in U.S. only for patients with facial fat loss due to HIV. Approved in other countries for wrinkles.	Low risk of allergies. Treatment effects can last 18 - 24 months.	Doctors require special training.

The popularity of Botox injections has skyrocketed in the United States. Between 2004 and 2005, the number of procedures performed jumped 16 percent. Botox injection was the number one non-surgical cosmetic procedure in 2005, with more than 3.2 million injections. Botulinum, the deadly toxin found in uncooked foods, is also a powerful muscle-relaxant. Tiny amounts of a purified form (Botox) are injected into wrinkles to relax the surrounding muscles. It may benefit forehead and frown lines, crow's feet, lower eyelids, lines on the side of the nose, and the area between the upper lip and the nose. It is also useful for treating involuntary muscle movements that can occur after a face-lift.

The injections need to be repeated every few months, since the effects wear off. The treatment decreases the ability to frown or squint and may cause the corners of the mouth to turn down. When used for areas around eyes, it produces a rounder appearance afterward, which patients should be aware of before they undertake the procedure.

The drug does not cross the blood-brain barrier, and, to date, the only side effects are temporary muscle weakness near the injection site. Although there have been some reports that Botox can reduce migraine and tension headaches, Botox also causes headaches in about 1% of cases. In some cases, the headaches can be very severe and long lasting (from 8 days to a month). Some researchers suggest that either a contaminated batch of Botox or a specific injection technique may be the cause, but additional investigation is needed.

Plastic Surgery

In 2005, there were over 2.1 million cosmetic surgeries, up 1% from the year before. Most of these surgeries were liposuction and breast surgeries. However, over 200,000 each of eyelid and nose surgeries were performed. Facial plastic surgeries range from being fairly minimal, such as a brow lift, to a full face-lift.

Several face-lift procedures (called rhytidectomies) are available. Face-lifts can provide individuals with a more youthful look. The degree of improvement, however, depends on many factors, including age, bone structure, skin type, and personal habits, such as smoking and sunbathing.

The Procedure. When a face-lift is a relatively simple procedure, it can take about 2 hours under local anesthetic in a doctor's office. Complicated face-lifts are done under general anesthesia in a hospital and can take 3 - 6 hours. The face-lift procedure may be one of the following:

Superficial musculoaponeurotic system (SMAS) is the most common face-lift procedure. The surgeon makes an incision at the hairline and separates the skin from the underlying tissue and muscles. The muscles are tightened and excess fat and tissue, such as fat under the chin and neck, are removed.
The endoscopic subperiosteal or subgaleal face-lift is a less invasive surgical technique. The surgeon raises facial structures rather than cutting away flaps of skin. Only a few half-inch incisions are made, and scarring is minimal. Not all individuals are candidates for this procedure, however.

Neither SMAS nor the endoscopic version is effective for the middle part of the face, particularly the deep lines (naso-labial folds) that run down from the nose beside the mouth. Some time after the SMAS face-lift, the upper face begins to age again while the lower area keeps its shape, causing the face to look imbalanced. Researchers are looking at other approaches, such as one called composite face-lift, that lift most muscles in the face.

Recovery Process. Recovery normally lasts from several weeks to several months. Swelling and discoloration are common. Some patients report tingling or numbing sensations after surgery. These sensations generally decrease as damaged nerves regenerate.

Complications. A face-lift is not without risks. A postsurgical hematoma is a collection of blood that can occur after a face-lift. In one study, major hematomas occurred in 2.2% of patients and minor hematomas in 6.65% of patients. They generally develop within 2 weeks of the surgery and require draining. Even minor hematomas need fast treatment to prevent greater complications. Such complications can include infection, changes in skin color, fluid buildup, and prolonged recovery time.

Other less common complications may include the following:

Infection
Excessive bleeding
Imbalanced facial muscles
Delayed healing
Scarring
Permanent injury to the nerves that control facial movements

These complications are rare, particularly with a skilled surgeon, but the more complex the face-lifts, the greater the risk.

Blepharoplasty. Blepharoplasty is the primary surgical procedure for eye lifts. Results usually last 5 -10 years. Although simple, it has potential complications, including permanent difficulty in closing the eyes or making a stern expression. Newer techniques, however, are preventing this complication. Assuming the surgeon is experienced, laser surgery is now preferred to the standard surgical scalpel approach. Laser surgery reduces bleeding and bruising, and both the operation and recovery are faster. Temporary blurred or double vision is common. More serious complications include infection, bleeding, dry eyes, difficulty in closing the eyes, and pulling down of the lower lids. Rare cases of blindness have been reported.

Transconjunctival Upper Blepharoplasty. An innovative procedure called transconjunctival upper blepharoplasty removes fat from the membrane that lines the eyelids (the conjunctiva) and is an effective technique for treating both the upper and lower eyelids. Unlike traditional blepharoplasty, this procedure does not cause scarring in the nasal area. In patients who have scars from previous surgeries, transconjunctival removal of fat can also make existing scars less obvious. Long-term side effects and effectiveness of this procedure have not been studied.

Laser Liposculpture and Platysma Resurfacing. A procedure called laser neck and jowl liposculpture and platysma resurfacing may prove to be an alternative to face-lifts. The procedure requires only a one-inch incision under the chin and removing excess fat. After the fat is removed, the surgeon tightens the platysma, the thin muscular sheet under the skin of the neck, which improves the shape of the neck. Only local anesthetic is needed, and the patient can return to normal activities in 2 days. The patient's skin should be elastic enough to be able to reform without sagging.

Resources

www.aad.org -- American Academy of Dermatology
www.asds.net -- American Society for Dermatologic Surgery
www.plasticsurgery.org -- American Society of Plastic and Reconstructive Surgeons
www.surgery.org -- American Society for Aesthetic Plastic Surgery
www.skincarephysicians.com/agingskinnet -- Aging Skin Net

References

Autier P, Gandini S. Vitamin D Supplementation and Total Mortality : A Meta-analysis of Randomized Controlled Trials. Arch Intern Med. 2007;167:1730-1737.

Cho HS, Lee MH, Lee JW, et al. Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiation. Photodermatol Photoimmunol Photomed. 2007;23(5):155-62.

Edison BL, Green BA, Wildnauer RH, Sigler ML. A polyhydroxy acid skin care regimen provides antiaging effects comparable to an alpha-hydroxyacid regimen. Cutis. 2004;73(2 Suppl):14-17.

Gordon, ML. A conservative approach to the nonsurgical rejuvenation of the face. Dermatol Clin. 2005 Apr;23(2):365-71.

Helfrich YR, Yu L, Ofori A, et al. Effect of smoking on aging of photoprotected skin: evidence gathered using a new photonumeric scale. Arch Dermatol. 2007;143(3):397-402.

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Review Date:
10/23/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Diabetes - type 1

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Life-Threatening Complicati...
Diagnosis
Dietary Goals and Exercise...
Treatment
Monitoring Tests
Long-Term Complications
Transplantation Procedures...
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Continuous Glucose Meter System

In 2007, the FDA approved the STS-7 System, which monitors glucose levels every 5 minutes during a 7-day period. The STS-7 System, like other continuous glucose meter systems, is designed to be used in combination with traditional fingerstick tests and meters. It does not replace them. But the system can track trends and fluctuation patterns in blood sugar levels that fingerstick tests cannot detect.

Type 1 Diabetes Gene Discovered

In 2007, scientists announced the discovery of a gene that may increase the risk of developing childhood type 1 diabetes.

Anemia Drugs Warning

In 2007, following the publication of several studies in the New England Journal of Medicine, the FDA warned that erythropoiesis-stimulating drugs (used to treat anemia) can increase the risk for blood clots, strokes, and heart attacks when excessive doses are given. The FDA has set new dosing and hemoglobin target levels for these drugs. Anemia is a common complication of end-stage kidney disease.

Cell Transplantation Research

Islet cell transplantation using the Edmonton protocol is a promising treatment for type 1 diabetes, suggests a 2006 study published in the New England Journal of Medicine. The Edmonton protocol involves isolating islet cells from donor pancreases and then injecting the cells into the patient. In the first international multicenter trial of this investigational procedure, 44% of 36 patients were able to temporarily suspend insulin injections, while 28% achieved partial islet function.
Stem cell transplantation using cells harvested and re-infused from the patient’s own body may help increase beta cell function and eliminate the need for insulin injections, according to a small, preliminary study published in 2007 in the Journal of the American Medical Association.

Type 1 Diabetes Prevention Research

Scientists around the world are investigating new ways to prevent type 1 diabetes or at least delay its onset. Experimental preventive measures include treatment with oral insulin and with drugs that may prevent the immune system’s attack on beta cells.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes.

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:

During and immediately after a meal the process of digestion breaks carbohydrates down into sugar molecules (of which glucose is one) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply. (Glucose levels after a meal are called postprandial levels.)
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 20 minutes after a meal insulin rises to its peak level.
Insulin enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (It should be noted that the brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

The pancreas is located behind the liver and stomach. In addition to secreting digestive enzymes, the pancreas secretes the hormones insulin and glucagon into the bloodstream. The release of insulin into the blood lowers the level of blood glucose (simple sugars from food) by enhancing glucose to enter the body cells, where it is metabolized. If blood glucose levels get too low, the pancreas secretes glucagon to stimulate the release of glucose from the liver.

In type 1 diabetes, the disease process is more severe than with type 2 diabetes, and onset is usually in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."
Patients become dependent on administered insulin for survival.

Type 2 diabetes is the most common form of diabetes, accounting for 90% of cases. About 20 million Americans have type 2 diabetes and half are unaware they have it. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that it may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin, and in the beginning this amount is usually sufficient to overcome such resistance.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

Maturity-Onset Diabetes in Youth. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. It accounts for 2 - 5% of type 2 cases.

Gestational Diabetes. An estimated 5% of pregnant women develop a form of type 2 diabetes in their third trimester called gestational diabetes. Gestational diabetes is usually temporary. [See In-Depth Report #60: Diabetes - type 2.]

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta-blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes, and others) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) also increase the risk for diabetes.

Causes

Type 1 diabetes is usually a progressive autoimmune disease, in which the beta cells that produce insulin are slowly destroyed by the body's own immune system. It is unknown what first starts this cascade of immune events, but evidence suggests that both a genetic predisposition and environmental factors, such as a viral infection, are involved.

Islets of Langerhans contain beta cells and are located within the pancreas. Beta cells produce insulin which is needed to metabolize glucose within the body.

Certain factors are thought to be important in this process:

White blood cells called T lymphocytes produce immune factors called cytokines that attack and gradually destroy the beta cells of the pancreas. Important cytokines are interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma.
Specific proteins are also critical in the process. They include glutamic acid decarboxylase (GAD), insulin, and islet cell antigens. These proteins serve as autoantigens. That is, they trigger the self-attack of the autoantibodies on the body's own beta cells.

Progression from the first stage, known as insulitis, to full-blown diabetes can take 7 years or longer. Unfortunately, by the time a person is aware that something is wrong and goes to the doctor with symptoms of type 1 diabetes, about 80 - 90% of the beta cells have been destroyed.

More than half of patients with insulitis do not develop diabetes. Researchers are greatly interested in discovering any factors that prevent the disease.

Researchers have found at least 18 genetic locations, labeled IDDM1 - IDDM18, that are related to type 1 diabetes. The IDDM1 region contains the HLA genes that encode proteins called major histocompatibility complex. The genes in this region affect the immune response. New advances in genetic research are identifying other genetic components of type 1 diabetes. In 2007, scientists announced that they had discovered a gene, KIAA0350, on chromosome 16. Variations in this gene appear to increase the risk of a child developing type 1 diabetes. The research team expects to identify an additional 15 - 20 genes associated with type 1 diabetes.

The odds of inheriting the disease, however, are only 10% if a first-degree relative has diabetes, and even in identical twins, one twin has only a 33% chance of having type 1 diabetes if the other has it. Children are more likely to inherit the disease from a father with type 1 diabetes than from a mother with the disorder.

Genetic factors cannot fully explain the development of diabetes. Over the past 30 years, a major increase in the incidence of type 1 diabetes has been reported in certain European countries, and the incidence has nearly tripled in the northeastern U.S. If genetic factors were the only cause of type 1 diabetes, such an increase in cases would take at least 400 years.

Some researchers believe one or more viral infections may trigger the disease in genetically susceptible individuals. Researchers suggest the following scenario:

An infection introduces a viral protein that resembles a beta-cell protein.
T cells and antibodies are tricked by this resemblance into attacking the beta protein as well as the virus.

Among the viruses under scrutiny are enteric viruses, which attack the intestinal tract. Coxsackieviruses are a family of enteric viruses of particular interest. (One study has suggested that respiratory infection in a child's first year, and not later, may be protective against diabetes, perhaps by priming the immune response so that it is better able to respond later on to other organisms.)

Risk Factors

An estimated 1 million people in the U.S. have type 1 diabetes, with about 30,000 new cases diagnosed each year. It is much less common than type 2, however, consisting of only 5 - 10% of all cases of diabetes. Nevertheless, like type 2 diabetes, the incidence of type 1 diabetes among children and adolescents has been rising over the past few decades. Experts estimate that about 1 in every 400 - 600 children and adolescents has type 1 diabetes. While type 2 diabetes has been increasing among African-American and Hispanic adolescents, the highest rates of type 1 diabetes are found among Caucasian youth.

Type 1 can occur at any age but usually appears between infancy and the late 30s, most typically in childhood or adolescence. Boys and girls are equally vulnerable. Studies report the following may be risk factors for developing type 1 diabetes:

Being ill in early infancy.
Early foods. Some studies have reported that early exposure to cow's milk in infancy and not being breast fed increased the risk for type 1 diabetes. Two studies in 2003 suggested that very early exposure to cereal -- not cow's milk -- plays a role in risk. Any risk from early dietary factors is still very low and likely to affect children who already have a genetically impaired immune response to dietary proteins. Breast milk contains factors that may help regulate the immune response and prevent diabetes in such children. National differences in risk also suggest that not all cow's milk is the same, and some proteins may confer higher risks than others.
Having a parent with type 1 diabetes.
Having an older mother.
Having a mother who had preeclampsia during pregnancy.
Obesity in children has long been linked to a higher risk for type 2 diabetes. Two 2001 studies reported an association between high weight at birth and obesity during childhood as risk factors for type 1 diabetes as well. The common risk factor may be an increase in insulin secretion, which occurs with obesity. This theoretically could overstress the beta cells so that they become susceptible to damage by overactive immune factors (particularly cytokines), and eventually to destruction in children genetically vulnerable to type 1 diabetes.

Until recently, diabetes in children was almost always type 1 diabetes. Of major concern, however, are estimates that between 8 - 45% of new diabetes cases in children are now type 2, most likely because of the increase in childhood obesity. [See In-Depth Report #60: Diabetes - type 2.]

The incidence of type 1 diabetes is higher than average among people with other autoimmune diseases, including Grave's disease, Hashimoto's thyroiditis (a form of hypothyroidism), Addison's disease, multiple sclerosis (MS), and pernicious anemia. Research has raised the possibility that all autoimmune diseases share a common genetic basis. A 2001 study found, for example, that the T-cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Both diseases have been associated with cow's milk protein. Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders or why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

There is a very wide variation in incidence of type 1 among population groups. Type 1 diabetes appears to be most common in people of northern European descent and in specific Mediterranean groups (such as Sardinians). It is less common among Asians and African-Americans. Still, African-Americans with type 1 diabetes are 50% more likely to die from it than Caucasians, mostly due to lower-quality health care.

Symptoms

The process that destroys the insulin-producing beta cells can be long and insidious. At the point when insulin production bottoms out, however, type 1 diabetes usually appears suddenly and progresses quickly. Warning signs of type 1 diabetes include:

Frequent urination (in children, a recurrence of bed-wetting after toilet training has been completed)
Unusual thirst, especially for sweet, cold drinks
Extreme hunger
Sudden, sometimes dramatic, weight loss
Weakness
Extreme fatigue
Blurred vision or other changes in eyesight
Irritability
Nausea and vomiting (acute symptoms)

Children with type 1 diabetes may also be restless, apathetic, and have trouble functioning at school. In severe cases, diabetic coma may be the first sign of type 1 diabetes.

Life-Threatening Complications

Diabetic ketoacidosis (DKA) is a life-threatening complication that develops when insulin stores are depleted. It is almost always caused by noncompliance with insulin treatments. Other contributing factors are lack of health insurance and intentionally reducing insulin levels in order to lose weight. In one study, adolescent girls were at higher risk for ketoacidosis than other groups of children and young people.

Diabetic ketoacidosis often develop as follows:

The process is usually triggered in insulin-deficient patients by a stressful event, most often pneumonia or urinary tract infections. Other triggers include alcohol abuse, physical injury, pulmonary embolism, heart attacks, or other illnesses.
Severely low insulin levels cause excessive amounts of glucose in the bloodstream (hyperglycemia).
Fat breakdown then accelerates and increases the production of fatty acids.

These fatty acids are converted into chemicals called ketone bodies, which are toxic at high levels. Symptoms and complications include:

Nausea and vomiting
Deep and rapid breathing may with frequent sighing
Rapid heartbeat
Cerebral edema, or brain swelling, is a rare but very dangerous complication that occurs in 1% of ketoacidosis cases and results in coma, brain damage, or death in many cases. Research now suggests that the risk for this complication is significantly higher in children with severe ketoacidosis (indicated by low carbon dioxide levels and high nitrogen urea levels), and possibly if they are also treated with bicarbonate to reduce acid levels.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.
If the condition persists, coma and eventually death may occur, although over the past 20 years, death from DKA has decreased to about 2% of all cases.

Life-saving treatment uses rapid rehydration with a salt (saline) solution followed by low-dose insulin and potassium replacement.

Ketoacidosis is a serious condition of glucose build-up in the blood and urine. A simple urine test can determine if high ketone levels are present.

Tight blood sugar (glucose) control increases the risk of low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, occurs if blood glucose levels fall below normal. Hypoglycemia may also be caused by insufficient intake of food, or excess exercise or alcohol. Usually the condition is manageable, but occasionally, it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms.

Risk Factors for Severe Hypoglycemia. Among young patients, the youngest children and boys of any age are at higher risk for hypoglycemia. Specific risk factors for severe hypoglycemia include:

Intensively controlling blood glucose and HbA1c levels
Having long-term diabetes
Being less educated about the condition
Being underinsured
Having psychiatric disorders

Hypoglycemia unawareness. Hypoglycemia unawareness is a condition in which people become insensitive to hypoglycemic symptoms. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Sweating
Trembling
Hunger
Rapid heartbeat

Severely low blood glucose levels can cause neurologic symptoms such as:

Confusion
Weakness
Disorientation
Combativeness
In rare and worst cases, coma, seizure, and death

Preventive Measures. The following tips may help avoid hypoglycemia or prepare for attacks.

Nocturnal hypoglycemia (which occurs during sleep) is a common problem for children, even those on nonintensive insulin therapy. (The risk for hypoglycemia is high in any case in children.) Bedtime snacks are advisable if blood glucose levels are below 180 mg/dL (10 mmol/L). Protein snacks may be best. (The use of the insulin pump may help prevent hypoglycemic episodes.)
Some research has suggested that children (particularly thin children) are at higher risk for hypoglycemia because the injection goes into muscle tissue. Pinching the skin so that only fat (and not muscle) tissue is gathered or using shorter needles may help.
Various insulin regimens are available that can reduce the risk. For example, taking a fast-acting insulin (insulin lispro) before the evening meal may be particularly helpful in preventing hypoglycemia.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who are at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes.

Family and friends should be aware of the symptoms and be prepared:

If the patient is helpless (but not unconscious), family or friends should administer three to five pieces of hard candy, two to three packets of sugar, half a cup (four ounces) of fruit juice, or a commercially available glucose solution.
If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment, possibly including the intravenous administration of a glucose solution.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see an example of a glucagon kit.

Experts have been concerned that the increased incidence of hypoglycemia accompanying strict blood glucose control could cause mental deterioration over time, but a 6-year study has found no evidence of this in adolescents and adults. (The effect on young children, however, is not known.)

Diagnosis

Fasting Plasma Glucose. The fasting plasma glucose (FPG) test is the standard test for diagnosing diabetes. It is a simple blood test taken after 8 hours of fasting. In general, results indicate the following:

FPG levels are considered normal up to 100 mg/dL (or 5.5 mmol/L).
Levels between 100 - 125 mg/dL (5.5 - 7.0 mmol/L) are referred to as impaired fasting glucose or pre-diabetes. These levels are considered to be risk factors for type 2 diabetes and its complications.
Diabetes is diagnosed when FPG levels are 126 mg/dL (7.0 mmol/L) or higher.

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the tests are normal in people who have symptoms or risk factors for diabetes. For example, people who take the test in the afternoon and show normal results may actually have abnormal levels that would be revealed if they are tested in the morning.

Glucose Tolerance Test. The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some experts recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

It first uses an FPG test.
A blood test is then taken 2 hours later after drinking a special glucose solution.

The following results suggest different conditions:

OGTT levels are normal up to 140 mg/dL.
Levels between 140 - 199 mg/dL are referred to as impaired glucose tolerance or pre-diabetes.
Diabetes is diagnosed when OGTT levels are 200 mg/dL or higher.

Both the FPG and OGTT tests require that the patient not eat for at least 8 hours prior to the test.

The oral glucose tolerance test is used to diagnose diabetes. The first portion of the test involves drinking a special glucose solution. Blood is then taken several hours later to test for the level of glucose in the blood. Patients who have diabetes will have higher than normal levels of glucose in their blood.

Test for Glycated Hemoglobin. Another test examines blood levels glycated hemoglobin, also known as hemoglobin A1c (HbA1c). Measuring glycated hemoglobin is not currently used for an initial diagnosis, but it may be useful for determining the severity of diabetes.

The basis for its use as a diagnostic measurement in diabetes is as follows:

Hemoglobin is a protein molecule found in red blood cells. When glucose binds to it, the hemoglobin becomes modified, a process called glycation.
Glycation affects a number of proteins, and elevated levels of glycolated hemoglobin is strongly associated with complications of diabetes.
A glycated hemoglobin level of 1% above normal range identifies diabetes in 98% of patients. Normal HbA1c levels do not necessarily rule out diabetes, but if diabetes is present and levels are normal, the risk for complications is low.

The test is not affected by food intake so it can be taken at any time. A home test has been developed that might make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%.
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Testing for Insulin Resistance. Investigators hope that some day a simple test for insulin resistance will be available to identify people at risk for diabetes. Some research suggests that measuring insulin and triglyceride levels during a fasting period may predict a person's sensitivity to insulin.

Type 1 diabetes is characterized by the presence of a variety of antibodies that attack the islet cells. These antibodies are referred to as autoantibodies because they attack the body's own cells -- not a foreign invader. Blood tests for these autoantibodies can help differentiate between type 1 and type 2 diabetes.

Screening for Heart Disease. All patients with diabetes should be tested for high blood pressure (hypertension) and unhealthy cholesterol and lipid levels and given an electrocardiogram. For cholesterol, people with diabetes should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Blood pressure goals should be 130/80 mmHg or lower. Other tests may be needed in patients with signs of heart disease.

High blood pressure is strongly associated with diabetic nephropathy (kidney disease). In fact, patients with type 2 diabetes who show signs of microalbuminuria typically already have hypertension. Type 1 diabetes patients with microalbuminuria, on the other hand, usually have normal blood pressure readings in the doctor's office. A 2002 study using home monitors, however, found that in patients with type 1 diabetes, high systolic blood pressure during sleep often occurs before development of nephropathy. (Systolic pressure is the first and higher number in a blood pressure reading.) Home blood pressure monitoring, may help identify patients with type 1 diabetes who are at risk for kidney damage.

Click the icon to see an image of an ECG.

Screening for Kidney Damage. The earliest manifestation of kidney disease is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. Microalbuminuria is also a marker for other complications involving blood vessel abnormalities, including heart attack and stroke.

The American Diabetes Association recommends that people with diabetes receive an annual microalbuminuria urine test. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleaning the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 1 diabetes have an annual comprehensive eye exam, with dilation, to check for signs of retina disease (retinopathy). Patients at low risk may need exams only every 2 - 3 years.

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who have loss of sensation in their feet should have a foot exam every 3 - 6 months to check for ulcers or infections.

Screening for Thyroid Abnormalities. Thyroid function tests should be administered.

Dietary Goals and Exercise

The treatment goals for a diabetes diet are:

Achieve near-normal blood glucose levels. People with type 1 diabetes must coordinate calorie intake with medication or insulin administration, exercise, and other variables to control blood glucose levels. New forms of insulin now allow more flexibility in timing meals.
Protect the heart and aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure.
Achieve reasonable weight. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Children, pregnant women, and people recovering from illness should be sure to maintain adequate calories for health.
Manage or prevent complications of diabetes. People with diabetes, whether type 1 or 2, are at risk for a number of medical complications, including heart and kidney disease. Dietary requirements for diabetes must take these disorders into consideration.
Promote overall health.

Overall Guidelines. There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 – 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists
Fats should provide 25 – 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 – 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat

[See In-Depth Report #42: Diabetes diet.]

Weight gain is a potential side effect of intense diabetic control with insulin. Being overweight can increase the risk for health problems. On the other hand, studies suggest that more than one-third of women with diabetes omit or underuse insulin in order to lose weight. Eating disorders have become a serious problem within the general population and are especially dangerous in patients with diabetes. Some evidence suggests that they contribute to about 20% of cases of recurrent ketoacidosis in young women. Ketoacidosis is a significant complication of insulin depletion and can be life threatening.

Aerobic exercise has significant and particular benefits for people with type 1 diabetes. It increases sensitivity to insulin, lowers blood pressure, improves cholesterol levels, and decreases body fat. Because glucose levels swing dramatically during workouts, people with type 1 diabetes need to take certain precautions:

Monitor glucose levels carefully before, during, and after workouts.
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
To avoid hypoglycemia, inject insulin in sites away from the muscles they use the most during exercise.
Before exercising, avoid alcohol and if possible certain drugs, including beta-blockers, which increase the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates, especially in the form of pre-exercise snacks. Skim milk is particularly helpful. They should also drink plenty of fluids.
Good, protective footwear is essential to help avoid injuries and wounds to the feet.

Resistance or high impact exercises should be avoided. They can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet. Because patients with diabetes may have silent heart disease, they should always check with their doctors before undertaking vigorous exercise.

A 2006 study of over 19,000 children with type 1 diabetes found that regular physical activity helps improve blood sugar levels without increasing the risk of severe hypoglycemia. The researchers suggest that doctors recommend regular exercise for pediatric patients with type 1 diabetes.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Treatment

Insulin is essential for strict control of blood glucose levels in type 1 diabetes. Tight blood glucose control is the best way to prevent major complications in type 1 diabetes including those that affect the kidneys, eyes, nerve pathways, and blood vessels. Intensive insulin treatment in early diabetes may even help preserve any residual insulin secretion for at least 2 years.

There are, however, some significant problems with intensive insulin therapy:

There is a higher risk for low blood sugar (hypoglycemia).
Many patients experience significant weight gain from insulin administration, which may have adverse effects on blood pressure and cholesterol levels. It is important to manage heart disease risk factors that might develop as a result of insulin treatment.

A diet plan that compensates for insulin administration and supplies healthy foods is extremely important. [See In-Depth Report #42: Diabetes diet.] Pancreas transplantation eventually may be recommended for patients who cannot control glucose levels without frequent episodes of severe hypoglycemia.

The goal of intensive insulin therapy is to keep blood glucose levels as close to normal as possible. In one major study, even when levels were 40% higher than nondiabetic levels, benefits were still observed.


	Normal	Goal
Blood glucose levels before meals	Less than 110 mg/dL (or 6.1 mmol/L)	90 - 130 mg/dL (or 5 - 7.2 mmol/L)
Bedtime blood glucose levels	Less than 120 mg/dL (6.6 mmol/L)	110 - 150 mg/dL (or 6.1 - 8.3 mmol/L)
Glycated hemoglobin (HbA1c) levels	4 - 6%	Less than 7%
Source: National Diabetes Information Clearinghouse, National Institutes of Diabetes and Digestive and Kidney Diseases.

Standard insulin therapy usually consists of one or two daily insulin injections, one daily blood sugar test, and visits to the health care team every 3 months. For strictly controlling blood glucose, however, intensive management is required. The regimen is complicated although newer insulin forms may make it easier.

There are two components to flexible insulin administration and a number of variations of insulin delivery for accomplishing them:

Basal insulin administration. The basal component of the treatment attempts to provide a steady amount of background insulin throughout the day. Basal insulin levels maintain regular blood glucose needs. Insulin glargine now offers the most consistent insulin activity level, but other intermediate and long-acting forms may be beneficial when administered twice a day. Short-acting insulin delivered continuously using a pump is proving to a very good way to provide basal rates of insulin.
Mealtime insulin administration. Meals require a boost (a bolus) of insulin to regulate the sudden rise in glucose levels after a meal.

In achieving insulin control the patient must also take other steps:

The patient should perform four or more blood glucose tests during the day.
Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
Insulin requirements vary depending on many non-nutritional situations during the day, including exercise and sleep. People are at enhanced risk for low blood sugar during exercise. Some patients experience a sudden rise in blood glucose levels in the morning -- the so-called "dawn phenomenon."
The patient must also maintain a good diet plan and should visit the health care team of doctors, nurses, and dietitians once a month.

Because of the higher risk for hypoglycemia in children, experts recommend that intensive treatment be used very cautiously in children under 13 and not at all in very young children.

Insulin cannot be taken orally because the body's digestive juices destroy it. Injections of insulin under the skin ensure that it is absorbed slowly by the body for a long-lasting effect. The timing and frequency of insulin injections depend upon a number of factors:

The duration of insulin action. Insulin is available in several forms, including: standard, intermediate, long-acting, and rapid-acting.
Amount and type of food eaten. Ingestion of food makes the blood glucose level rise. Alcohol lowers levels.
The person's level of physical activity. Exercise lowers glucose levels.

Fast-Acting Insulin. Insulin lispro (Humalog) and insulin aspart (Novo Rapid, Novolog) lower blood sugar very quickly, usually within 5 minutes after injection. Insulin peaks in about 4 hours and continues to work for about 4 hours. This rapid action reduces the risk for hypoglycemic events after eating (postprandial hypoglycemia). Optimal timing for administering this insulin is about 15 minutes before a meal, but it can be also taken immediately after a meal (but within 30 minutes). Fast-acting insulins may be especially useful for meals with high carbohydrates.

Regular Insulin. Regular insulin begins to act 30 minutes after injection, reaches its peak at 2 - 4 hours, and lasts about 6 hours. Regular insulin may be administered before a meal and may be better for high-fat meals.

Intermediate Insulin. NPH (neutral protamine Hagedorn) insulin has been the standard intermediate form. It works within 2 - 4 hours, peaks 4 - 12 hours later, and lasts up to 18 hours. Lente (insulin zinc) is another intermediate insulin that peaks 4 - 12 hours and lasts up to 18 hours.

Long-Acting (Ultralente) Insulin. Long-acting insulins, such as insulin glargine (Lantus), are released slowly. Insulin glargine matches parts of natural insulin and maintains stable activity for more than 24 hours. Studies suggest that it poses less of a risk for hypoglycemia and weight gain than NPH. It has a higher incidence of pain at the injection site than NPH. Ultralente insulin peaks at 10 hours and lasts up to 20 hours but varies greatly in activity from day to day.

Combinations. Regimens generally include combinations of short and longer-acting insulins to help match the natural cycle. For example, one approach in patients who are intensively controlling their glucose levels uses 3 injections of insulin, which includes a mixture of regular insulin and NPH at dinner. Another approach uses 4 injections, including a separate short-acting form at dinner and NPH at bedtime, which may pose a lower risk for nighttime hypoglycemia than the 3-injection regimen.

Insulin Pumps. An insulin pump can improve blood glucose control and quality of life with fewer hypoglycemic episodes than multiple injections. The pumps correct for the “dawn phenomenon” (sudden rise of blood glucose in the morning) and allow quick reductions for specific situations, such as exercise. Many different brands are available.

The typical pump is about the size of a beeper and has a digital display. Some are worn externally and are programmed to deliver insulin through a catheter in the skin or the abdomen. They generally use rapid-acting insulin, the most predictable type. They work by administering a small amount of insulin continuously (the basal rate) and a higher dose (a bolus dose) when food is eaten.

Many adults, adolescents, and school children use insulin pumps. A 2006 study found that even very young children (ages 2 - 7 years) can successfully use insulin pumps and that the pumps provided better blood sugar control than twice-daily insulin injections.

The catheter at the end of the insulin pump is inserted through a needle into the abdominal fat of a person with diabetes. Dosage instructions are entered into the pump's small computer, and the appropriate amount of insulin is then injected into the body in a calculated, controlled manner.

Learning to use the pump can be complicated, although over time most patients find the devices are fairly easy to use. To achieve good control, patients and parents of children must undergo some training. The patient and doctor must determine the amount of insulin used -- it is not automatically calculated. This requires an initial learning period, including understanding insulin needs over the course of the day and in different situations and knowledge of carbohydrate counting. Frequent blood testing is very important, particularly during the training period.

Insulin pumps are more expensive than insulin shots and occasionally have some complications, such as blockage in the device or skin irritation at the infusion site. In spite of early reports of a higher risk for ketoacidosis with pumps, more recent studies have found no higher risk.

Insulin Pens. Insulin pens, which contain cartridges of insulin, have been available for some time. Until recently, they were fairly complicated and difficult to use. Newer, prefilled pens (Humulin Pen, Humalog) are disposable and allow the patient to dial in the correct amount.

Inhaled Aerosol. In 2006, the FDA approved the first non-injected form of insulin. Exubera is an inhaled form of insulin. It is approved for adults but should not be used by patients who smoke or have quit smoking within the past 6 months. Patients with asthma, bronchitis, or emphysema should also not use inhaled insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

Other Alternative Insulin Delivery Methods. Another promising avenue of investigation for delivering insulin is the use of ultrasound pulses.

Pramlintide (Symlin) is a new type of injectable drug that can help control postprandial hyperglycemia, the sudden increase in blood sugar after a meal. Pramlintide is injected before meals and can help lower blood sugar levels in the 3 hours after meals. Pramlintide is used in addition to insulin for patients who take insulin regularly but still need better blood sugar control. The FDA approved this drug in 2005 for adults with type 1 and type 2 diabetes. Pramlintide and insulin are the only two drugs approved for treatment of type 1 diabetes.

Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Side effects may include nausea, vomiting, abdominal pain, headache, fatigue, and dizziness. Patients with type 1 diabetes have an increased risk of severe low blood sugar (hypoglycemia) that may occur within 3 hours following a pramlintide injection. This drug should not be used if patients have trouble knowing when their blood sugar is low or have slow stomach emptying (gastroparesis).

CD3-Antibodies. A new type of drug called a CD3 antibody is showing promise for helping patients newly diagnosed with type 1 diabetes. In phase II clinical trials, patients received the drug for 6 days. Results from a 2005 trial published in the New England Journal of Medicine indicated that the CD3 antibody helped stimulate the patients’ natural insulin production and decreased their need for insulin drug therapy. The beneficial effects lasted up to 18 months after CD3 treatment. Researchers think that this drug affects the autoimmune response involved in type 1 diabetes and helps preserve the residual beta cell function of the pancreas.

Monitoring Tests

Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to carefully monitor blood glucose levels. In general, patients with type 1 diabetes need to take readings four or more times a day. Patients should aim for the following measurements:

Pre-meal glucose levels of between 90 - 130 mg/dL
Bedtime levels of between 110 - 150 mg/dL

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Finger-Prick Test. A typical blood sugar test includes the following:

A drop of blood is obtained by pricking the finger.
The blood is then applied to a chemically treated strip.
Monitors read and provide results.

Home monitors are about 10 - 15% less accurate than laboratory monitors are and many do not meet the standards of the American Diabetes Association. Most doctors believe, however, that they are accurate enough to indicate when blood sugar is too low.

To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some simple procedures may improve accuracy:

Testing the meter once a month.
Recalibrating it whenever a new packet of strips is used.
Using fresh strips; outdated strips may not provide accurate results.
Keeping the meter clean.
Periodically comparing the meter results with the results from a laboratory.

Supplementary Monitoring Devices. Other devices are available for monitoring blood glucose. These devices are used in addition to traditional fingerstick test kits and glucose meters but do not replace them:

Continuous glucose monitoring systems (CGMS) use a needle-like sensor inserted under the skin of the abdomen to monitor glucose levels every 5 minutes. In 2007, the STS-7 System was approved. Using a disposable sensor, the STS-7 measures glucose levels for up to a week. An alarm will sound if glucose levels are too high or low. The older Minimed system measures glucose over a 72-hour period and has wireless communication between the monitor and an insulin pump.
GlucoWatch is a battery-powered wristwatch-like device that measures glucose by sending tiny electric currents through the skin, a technique called reverse iontophoresis. It is painless and has a warning device when detecting high glucose levels. It takes 2 hours to warm up, and the sensor pads need to be changed every day. Glucowatch measures glucose levels three times per hour for up to 12 hours. About a quarter of the time, the results differ significantly from actual fingerstick tests, however.

Hemoglobin A1c (also called HbA1c , HA1c, or A1C) is measured periodically every 2 - 3 months to determine the average blood-sugar level over the lifespan of the red blood cell. Normal A1C levels should be below 7%. Home tests are also available for measuring A1C.

Urine tests are useful for detecting the presence of ketones. These tests should always be performed during illness or stressful situations, when diabetes is likely to go out of control. The patient should also undergo yearly urine tests for microalbuminuria (small amounts of protein in the urine), a risk factor for future kidney disease.

Long-Term Complications

Type 1 diabetes reduces the normal lifespan by an average of 5 - 8 years. However, survival rates are improving in all ethnic groups and both genders. Longer survival rates are probably due to improvements in monitoring and tighter control of blood glucose. There are two important approaches to preventing complications from type 1 diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. This approach is proving to prevent complications due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
Managing risk factors for heart disease. Blood glucose control helps the heart, but it is also very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

Patients with type 1 diabetes have a 10 times greater risk of heart disease than healthy patients. Heart attacks account for 60% and strokes for 25% of deaths in patients with diabetes. Diabetes affects the heart in many ways:

Both type 1 and 2 diabetes accelerate the progression of atherosclerosis (hardening of the arteries). Diabetes can adversely affect blood lipid levels by lowering HDL ("good cholesterol") and increasing triglycerides. This can lead to coronary artery disease, heart attack, or stroke.
In type 1 diabetes, high blood pressure (hypertension) usually develops if the kidneys become damaged. High blood pressure is another major cause of heart attack, stroke, and heart failure. Children with diabetes are also at risk for hypertension.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions ranges from 15 - 53%.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Click the icon to see an image of the kidney.

Results from the Diabetes Control and Complications Trial (DCCT) prove that intensive blood sugar control reduces the long-term risk of heart disease complications by 50%. The results indicate that intensive blood sugar control is even more important in reducing these risks than blood pressure- and cholesterol-lowering drugs. Original participants in the trial received intensive blood glucose control for 6 years during the 1980s. Researchers continued to follow these patients’ progress during the next 17 years. A follow-up study, published in 2005 in the New England Journal of Medicine, found that the benefits of tight blood glucose control persisted over time and halved the risk of heart attack, stroke, angina, or coronary artery disease.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin reduces the risk for blood clotting and may help protect against heart attacks. In a 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes.

Reducing Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Dozens of anti-hypertensive drugs are available. Most fall into the following categories:

Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
Angiotensin-receptor blockers (ARBs) block angiotensin.
Beta-blockers block the effects of adrenaline and ease the heart’s pumping action.
Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

The American Diabetes Association (ADA) recommends any of these classes of drugs as first-line treatment for hypertension. New research suggests, however, that beta-blockers are less effective at preventing strokes and heart attacks than other types of blood pressure medications. ACE inhibitors are especially helpful for patients with type 1 diabetes as they may help prevent kidney disease (nephropathy).

Many patients require more than one type of drug to control blood pressure. For patients with diabetes who have microalbuminuria, the ADA strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).

Anti-hypertensive drugs that block or reduce angiotensin are the first option for many people with diabetes. Angiotensin is a natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure.

The 2005 landmark Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicated that a thiazide-type diuretic works as well as an ACE inhibitor or CCB for patients with type 2 diabetes and high blood pressure. Compared with ACE inhibitors or CCBs, diuretics appeared to be better at lowering systolic blood pressure and preventing heart failure. In addition, the trial suggested that diuretics are especially helpful for African-Americans, by offering greater protection than ACE inhibitors or CCBS in preventing strokes. [See In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances, including low HDL (“good”) cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor and generics), pravastatin (Pravachol), simvastatin (Zocor and generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels. Recent studies indicate that aggressive high-dose statin therapy may be an important treatment approach for high-risk patients who need to substantially lower their LDL levels. A 2006 study found that patients with diabetes and heart disease who were treated with 80 mg daily of atorvastatin had a 25% lower risk of heart attack and stroke than patients who received a 10 mg daily dose.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms.

Although lowering LDL cholesterol is beneficial, statins are not as effective as other medications -- such as fibrates, niacin, ezetimbe, or bile acid sequesters -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combining a statin with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care.

Fibrates, such as gemfibrozil (Lopid) and fenofibrate (Tricor), are usually the first choice. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, about 30% of patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [See In-Depth Report #23: Cholesterol.]

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Treatment and Prevention of Nephropathy. Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Long-term studies report that strict control of these two conditions produces a 60% reduction in new cases of nephropathy and a delay in progression of the disease. Research indicates that ACE inhibitors are the best class of blood pressure medications for delaying kidney disease and slowing disease progression in patients with type 1 diabetes. Angiotensin-receptor blockers (ARBs) are also very helpful.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally require higher amounts of protein. [See In-Depth Report #42: Diabetes diet.]

Diabetic nephropathy, the leading cause of end-stage renal disease (ESRD), occurs in about 20 - 40% of patients with diabetes. Patients with ESRD have 13 times the risk of death compared to other patients with type 1 diabetes. If the kidneys fail, dialysis is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color. On an encouraging note, a 2005 study in the Journal of the American Medical Association reported that the prognosis of end-stage renal disease has greatly improved during the last 4 decades for patients with type 1 diabetes. The outlook was best for patients who were diagnosed with diabetes at a young age (under 5 years old). In addition, the study found that fewer people with type 1 diabetes are developing ESRD.

Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually require injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. Patients with end-stage kidney disease should be aware of the current controversies surrounding the dosing of these drugs.

In 2006, two important New England Journal of Medicine studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia. In 2007, the FDA issued new warnings on darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). The warnings describe an increased risk for blood clots, strokes, and heart attacks in patients with end-stage kidney disease when these drugs were given at higher than recommended doses. The FDA has set new dosing and hemoglobin target levels for these drugs.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Maintain hemoglobin levels that do not exceed 12 g/dL
Receive frequent blood tests to monitor hemoglobin levels
Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure

[See In-Depth Report #57: Anemia.]

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral (affects nerves in the toes, feet, legs, hand, and arms)
Autonomic (affects nerves that help regulate digestive, bowel, bladder, heart, and sexual function)

Peripheral neuropathy particularly affects sensation. It is a common complication that affects nearly half of people with type 1 or type 2 diabetes after 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Tingling
Weakness
Burning sensations
Loss of the sense of warm or cold
Numbness (if the nerves are severely damaged, the patient may be unaware that a blister or minor wound has become infected)
Deep pain

Autonomic neuropathy can cause digestive problems (constipation, diarrhea, nausea, vomiting), bladder infections, and erectile dysfunction. In some cases, neuropathy may mask angina, the warning chest pain for heart disease and heart attack. Patients with diabetes should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

Blood sugar control is the only treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. A 2005 study also suggested that heart disease risk factors can increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

Pain-Relief Treatment for Peripheral Neuropathy. A number of different drugs are used for peripheral neuropathy pain relief: They include:

Nonprescription analgesics, such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately, tricyclics may cause heart rhythm problems.
Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, a newer type of antidepressant, which was approved in 2004 for treatment of pain associated with diabetic peripheral neuropathy.
The anti-convulsant drug pregabalin (Lyrica) was approved in 2004 for neuropathic pain management. It is classified as a controlled substance (like narcotics), which indicates a potential risk for abuse. Other anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin) and valproate (Depakote).

Treatments under investigation include acetyl-l-carnitine and intravenous alpha-lipoic acid. Patients may also benefit from transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments such as hypnosis, biofeedback, relaxation techniques, and acupuncture have helped some patients manage pain. Doctors also recommend lifestyle measures, such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy.

Erectile dysfunction is also associated with neuropathy. Studies indicate that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms.

Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of patients with diabetes experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations, 50 - 75% of them due to diabetes. The number is increasing as the prevalence in diabetes type 2 rises. According to a 2005 study in the Lancet, every 30 seconds someone in the world receives a lower limb amputation due to diabetes. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. A 2006 study reported that people with diabetes who develop foot infections are 155 times more likely to have an amputation than people who did not develop infections. Foot infections often develop from injuries. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

A 2003 government survey found that those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers. [See In-Depth Report #102: Peripheral artery disease and intermittent claudication.]

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in up to 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Charcot foot is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:

Patients should inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.
When washing the feet, the water should be warm (not hot) and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.
Moisturizers should be applied, but not between the toes.
Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.
Patients should not use medicated pads or try to shave the corns or calluses themselves.
Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of patients with diabetes wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole (LucRo) reduce pressure under the heel and front of the foot by 35 - 65% and may be particularly helpful. Custom-molded boots increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
Shoes should be changed often during the day.
Wear socks, particularly with extra padding (which can be specially purchased).
Patients should avoid tight stockings or any clothing that constricts the legs and feet.
Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
A specialist in foot care should be consulted for any problems.

Click the icon to see an image of foot inspection.

Treating Foot Ulcers in Diabetes. About one-third of foot ulcers will heal within 20 weeks with good wound care treatments. Some treatments are as follows:

Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
Felted foam may be helpful in healing ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, patients who had had ulcers that had not responded to treatment for over 3 months received daily treatments that lasted 90 minutes for 2 weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.
Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Diabetes accounts for 12,000 - 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults ages 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries -- probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.

The early and more common type of this disorder is called nonproliferative or background retinopathy. The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision.
If the capillaries become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These woolly areas may signal the development of proliferative retinopathy. Often there are no symptoms of progressing retinopathy. In this more severe condition, new abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2, although in one study over 20% had signs of retinopathy 6 years after diagnosis. In general, all patients with diabetes should have a yearly eye examination. Patients with no signs of retinal damage or low risk factors for retinopathy may only require screening every 2 - 3 years.

Click the icon to see an animation on diabetic retinopathy.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slow ability to do mental arithmetic.

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5 - 15% during flu epidemics, and they are six times more likely to be hospitalized with complications from flu than nondiabetic patients who have flu. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Diabetes doubles the risk for depression. Furthermore, depression, in turn, increases the risk for hyperglycemia and complications of diabetes, according to one study. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but may help patients control their blood sugar levels.

Diabetes changes bone quality and density, but the effects differ depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fractures. The best medications for bone loss in patients with diabetes are bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [See In-Depth Report #18: Osteoporosis.]
Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

Older patients with either type of diabetes are at risk for falling, which compounds the risk for fracture.

Diabetes increases the risk for other conditions, including:

Hearing loss
Periodontal disease
Carpal tunnel syndrome
Nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH); a particular danger for people who are obese
Colorectal cancer
Uterine cancer

Diabetes and Pregnancy. Both temporary diabetes that occurs during pregnancy (gestational diabetes) and pregnancy in a patient with existing diabetes can increase the risk for birth defects. Studies indicate that high blood sugar levels (hyperglycemia) may affect the developing fetus as soon as it is conceived.

Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes large amounts of insulin. This combination of high fetal blood levels of insulin and glucose can have significant effects:

Excessive fetal weight gain, which can lead to complications during delivery
Birth defects
Breathing problems and delayed lung development
Low blood sugar
Higher future risk for obesity and diabetes

In addition to endangering the fetus, diabetes also presents risks to the pregnant woman, particularly preeclampsia, which is a potentially dangerous condition involving very high blood pressure during pregnancy. Pregnant women with diabetes are also at greater risk for retinopathy.

Some recommendations for preventing complications include:

Intensive blood sugar control during pregnancy may reduce the risk for problems in the infant.
Monitoring blood glucose after meals may protect against preeclampsia more effectively than monitoring before meals.
Aerobic exercise before and during pregnancy can lower glucose levels. (All pregnant women, particularly those with diabetes, should check with their doctors before embarking on a rigorous exercise regimen.)
To prevent birth defects that affect the heart and nervous system, women with diabetes should take a higher dose of folic acid from the time of conception up to week 12 of pregnancy. They should also be checked for any heart problems.
Women with diabetes should have an eye examination during pregnancy and up to a year afterward.

Although there was some concern that short-acting insulin lispro might increase the risk for birth defects, the most recent evidence suggests that it does not. In fact, some experts believe it achieves a better outcome and should be preferred to regular insulin in pregnant women. More research is needed.

Effect on Estrogen. Diabetes appears to blunt some of the effects of estrogen, which may increase the risk for heart disease. Women with diabetes have a higher risk for early menopause, which, in one study, occurred at an average age of about 41 years.

Reproductive Cancers. Women with type 1 diabetes often have lumps in the breast that are benign but which make mammograms difficult to interpret. It is not clear whether these lumps are risk factors for breast cancer. One study indicated that women with diabetes have a higher risk for endometrial cancer and possibly for breast cancer.

Lack of Blood Glucose Control. Control of blood glucose levels is generally very poor in adolescents and young adults. Adolescents with diabetes are at higher risk than adults for ketoacidosis resulting from noncompliance. In a British study of young adults with type 1 diabetes, 15% were already hypertensive, and about half of these young people had signs of kidney damage. Young people who do not control glucose are also at high risk for permanent damage in small vessels, such as those in the eyes.

Self-Destructive Behaviors. One study found that young people with diabetes have a higher than average rate of suicidal fantasies. Although the actual rate of suicide was no higher than that of their nondiabetic peers, such thoughts are strongly associated with self-destructive behavior.

Of particular note, up to one-third of young women with type 1 diabetes have eating disorders and under-use insulin to lose weight. Anorexia and bulimia pose significant health dangers in any young person -- but they can be especially severe in people with diabetes.

Transplantation Procedures

Major advances in islet-cell transplantation are allowing more patients to come off insulin or reduce their use of it.

Major clinical trials are now using a specific islet-cell (also called beta-cell) transplantation procedure called the Edmonton protocol, which usually involves the following steps:

As soon as there are sufficient numbers of islets available for transplantation, the patient is given intravenous antibiotics and oral vitamins E, B6, and A.
A machine isolates islet cells taken from donor pancreases, generally from cadavers. Two or three organs are usually needed in order to supply enough islet cells to have any effect on insulin production. (This is a major limitation of the procedure.)
Once the islets have been isolated, they are injected directly in a major vein in the patient's liver.
The islets are carried to capillaries in the liver where they produce insulin.
Specific drugs, such as tacrolimus, sirolimus, or rapamycin (Rapamume), are used to suppress the immune system. (Unlike immunosuppressant drugs used in other transplantation procedures, these drugs do not contain steroids, which destroy islet cells.) Immunosuppressants are needed for the rest of the patient's life so that the body does not reject these foreign islet cells.
The procedure has to be performed two or more times over a period of 2 - 3 months. This generally requires multiple pancreas donors in order to achieve complete independence from insulin therapy. This is a major limitation to the procedure.

In 2006, the New England Journal of Medicine published the results of the first multicenter trial of the Edmonton protocol. The results indicated that this treatment may benefit some patients with severe type 1 diabetes. Of the 36 patients who underwent the transplant procedure, 44% no longer needed insulin injections a year after the final treatment. However, two-thirds of these insulin-independent patients needed to resume insulin injections within 2 years.

The Edmonton protocol achieved partial islet function in 28% of patients, which helped control hypoglycemic unawareness, a serious complication of diabetes. (In hypoglycemic unawareness, patients no longer recognize the symptoms of severe low blood sugar.) Even though these patients still needed insulin shots, they had better control of their diabetes. Researchers are continuing to work on refining the Edmonton protocol so that its benefits can be more sustainable and long lasting.

A major obstacle for the islet cell transplantation is the need for two or more donor pancreases to supply sufficient islet cells. Unfortunately, there are not enough pancreases available to make this procedure feasible for even 1% of patients. Researchers, then, are looking for alternative sources for islet cells. In one center, for example, researchers used pig islet cells as the donor source in children and did not administer immunosuppressant drugs. Half the children responded well to this approach. Another study reported that select patients may require only one donor.

Other research is focusing on umbilical cord cells, embryonic or adult stem cells, bone marrow transplantation, and other types of cellular therapies. These studies are still in very early stages, but experts predict that there will be major research advances in these fields in the coming years. A small, preliminary study published in 2007 in the Journal of the American MedicalAssociation looked at the effects of autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) in patients newly diagnosed with type 1 diabetes. AHST is an experimental treatment for type 1 diabetes. It involves treating a patient with high doses of drugs to suppress the immune system, then harvesting the patient’s own blood cells and re-infusing them back into the body. In the study, 14 out of 15 patients who underwent AHST were able to stop taking insulin shots.

Whole pancreas transplants and double transplants of pancreases and kidneys are proving to have a good long-term success rate for some patients with type 1 diabetes. The operations help to prevent further kidney damage, and long-term studies indicate that they may even eventually reverse some existing damage. There is some evidence that heart disease and diabetic neuropathy improve after pancreas transplantation (although not retinopathy). One 10-year study reported that survival rate at 10 years was 76%, and two-thirds of the patients had both pancreas and kidney function. Immunosuppressive drugs are needed lifelong with this procedure. Experts generally recommend transplants in cases of end-stage kidney failure or when diabetes poses more of a threat to the patient's life than the transplant itself.

Uncontrolled diabetes causes damage to many tissues of the body, including the kidneys. Kidney damage caused by diabetes most often involves thickening and hardening of the internal kidney structures. Strict blood glucose control may delay the progression of kidney disease in type 1 and type 2 diabetics.

Prevention

Fingerstick blood tests are now available that can test for autoantibodies that identify children who are at high risk for developing type 1 diabetes. At this time, however, there is no way to prevent type 1 diabetes, and all preventive therapies are investigative. Until there are ways to prevent the condition, such screening tests are expensive and provide little value.

Investigational approaches focus on preventing type 1 diabetes or at least delaying it as long as possible. Preventive measures are sometimes defined as primary and secondary:

Primary prevention attempts to preserve all beta cells before the disease process starts.
Secondary prevention aims to deter further beta cell destruction once it has started and before symptoms arise.

For primary prevention, one experimental approach involves oral insulin, which is taken as a pill once a day. Unlike insulin injections that lower blood sugar, oral insulin does not affect blood glucose levels because it is quickly broken down in the digestive system. It may, however, help calm the immune system and prevent its attack on beta cells. Another study is exploring whether docosahexaenoic acid (DHA), an omega-3 fatty acid, can help prevent development of autoimmune type 1 diabetes in newborns who are at high risk for the disease.

Secondary prevention focuses on preserving beta cells and their insulin-producing function. Researchers are exploring several treatments for patients who are newly diagnosed with type 1 diabetes. These experimental therapies include:

Rituximab (Rituxan), a monoclonal antibody drug used for treatment of rheumatoid arthritis and non-Hodgkin’s lymphoma, is being studied in patients with type 1 diabetes for its effects on disrupting the immune system’s attack on beta cells.
Immune-suppressing drugs, such as mycophenolate mofetil (MMF) alone or in combination with daclizumab (DZB), are used to prevent rejection in organ transplantation. Researchers hope that these drugs may be able to slow or stop the autoimmune disease process of type 1 diabetes.
CD3-antibody drug therapy is showing promise in retaining newly diagnosed patients’ natural insulin production and decreasing their need for insulin therapy.

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.jdrf.org -- Juvenile Diabetes Research Foundation
www.nei.nih.gov -- National Eye Institute
www.eatright.org -- American Dietetic Association
www.kidney.org -- National Kidney Foundation
www.diabetestrialnet.org -- Type 1 Diabetes International Clinical Trial Net
www.medicalert.org -- Bracelets or neck chain emblems with personal medical information
www.childrenwithdiabetes.com -- Children with diabetes online community

References

American Diabetes Association (ADA). Standards of medical care in diabetes. VI. Prevention and management of diabetes complications. Diabetes Care. 2007 Jan;30(Suppl 1):S15-24.

Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006 Nov 16;355(20):2071-84.

Hakonarson H, Grant SFA, Bradfield JP, Marchand L, Kim CE, Glessner JT, et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature. Published online 15 July 2007.

SEARCH for Diabetes in Youth Study Group , Liese AD, D'Agostino RB, Hamman RF, Kilgo PD, Lawrence JM, et al. The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006 Oct;118(4):1510-8.

Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30.

Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006 Nov 16;355(20):2085-98.

Skyler JS. Cellular therapy for type 1 diabetes: has the time come? JAMA. 2007 Apr 11;297(14):1599-600.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76.

Writing Group for the SEARCH for Diabetes in Youth Study Group , Dabelea D, Bell RA, D'Agostino RB, Imperatore G, Johansen JM, et al. Incidence of diabetes in youth in the United States. JAMA. 2007 Jun 27;297(24):2716-24.

Review Date:
7/19/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Multiple sclerosis

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
The Autoimmune Disease Proc...
Symptoms
Causes
Risk Factors
Complications
Diagnosis
Treatment
Drug Treatment
Other Treatments
Treating the Complications...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Gender and Multiple Sclerosis (MS)

MS is increasingly affecting women, according to research presented at the 2007 annual conference of the American Academy of Neurology. Researchers found that in the 1940s, women were twice as likely as men to be diagnosed with MS. By 2000, women were about four times more likely than men to develop MS. Experts are uncertain why this ratio is growing.

Family History

If MS runs in your family, there’s a chance you may develop the disease at the same age that other family members did, suggests a 2007 Neurology study. However, family history does not predict disease course or severity.

Vitamin D

Higher blood levels of vitamin D may reduce the risk for MS, at least among Caucasians, indicates a 2007 study in the Journal of the American Medical Association. (The researchers found no protective effect for African-Americans or Hispanics.) However, until further research is conducted, doctors do not recommend taking vitamin D supplements for MS prevention.

Infections and Symptom Relapse

Both viral and bacterial systemic infections can trigger relapses, according to a study in Neurology. Researchers found that relapses and new brain lesions appeared within 2 weeks after an infection.

Drug Research

Natalizumab (Tysabri) may help reduce vision loss in patients with relapse-remitting MS, indicates a 2007 Neurology study. In 2006, the FDA enforced safety restrictions on the use of this drug due to cases of progressive multifocal leukoencephalopathy (PML), a rare brain disorder. Since the restrictions were put in place, no new cases of PML have been reported.
Glatiramer acetate (Copaxone) shows little benefit for primary progressive MS, according to a 2007 study in Annals of Neurology.
Testosterone gel may help men with relapse-remitting MS, suggests a small study published in 2007 in the Archives of Neurology.

Introduction

Multiple sclerosis (MS) is a disease of the central nervous system (CNS), the nerves that comprise the brain and spinal cord. It has two major features:

Destruction of myelin, a fatty insulation covering the nerve fibers, is the main characteristic of MS. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. (Multiple sclerosis is well named. Sclerosis comes from the Greek word skleros, which means hard.)
Destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is also a major factor in the permanent disability that occurs with MS.

Myelin is the layer that forms around nerves. Its purpose is to speed the transmission of impulses along nerve cells.

The symptoms, severity, and course of MS vary widely depending partly on the sites of the plaques and the extent of the demyelination. Experts generally group multiple sclerosis into two major symptom categories:

Relapsing-remitting
Chronic-progressive

Chronic-progressive MS is often subcategorized as primary-progressive, secondary-progressive, and progressive-relapsing.

Recent evidence suggests that the disease process starts long before symptoms begin. By the time symptoms appear, there are often already signs of brain and spinal cord atrophy. The cause of MS is unknown, and it cannot be prevented or cured. It is not fatal, however, and great progress is being made in treating it and identifying underlying mechanisms that trigger this disease.

Relapsing-remitting multiple sclerosis generally occurs in younger people and is the most common form of MS. It generally follows this course:

Most patients first experience a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis.
The characteristic feature of relapsing-remitting MS is the attack (also referred to as relapse, flare-up, or exacerbation), which is a bout of specifically MS symptoms (facial pain, Lhermitte’s sign, or bladder instability) that lasts at least 24 hours and typically several days. Such attacks are fairly mild in about half of patients with this form of MS.
The disease then goes into remission (when symptoms improve or disappear), usually for about 4 - 8 weeks. To be considered in remission, attacks need to be separated by at least 30 days. Remission periods may be spontaneous or induced by immunosuppressive drugs. A person with multiple sclerosis in remission may have subtle attacks and not realize it. For example, hands may be a little numb for a few days, or there may be slight awkwardness in gait or coordination.
Remissions are almost always followed by relapses, in which symptoms flare-up or the patient experiences a period of deteriorating ability.

About 20% of patients with relapsing-remitting MS experience little or no progression after a first attack for long periods of time, although by 25 years most patients have converted to a progressive phase.

The term chronic-progressive multiple sclerosis is used to describe cases in which symptoms continue to worsen slowly without remission. About 20% of multiple sclerosis patients (usually those whose first symptoms occur after age 45) have the chronic-progressive form without first developing relapsing-remitting MS. Chronic-progressive MS generally follows a downhill course, but its severity varies widely. Three variants are commonly used to define this patient group:

Secondary-Progressive MS (SPMS). SPMS is the natural evolution of relapsing-remitting MS and develops in about half of patients during the first 10 years and nearly all of them within 25 years. It follows a progressive course of nerve and muscle deterioration with occasional acute flare-ups, remissions, and plateaus.
Primary-Progressive MS (PPMS). PPMS progresses continuously and gradually from the first onset of symptoms and has no remissions. It occasionally levels off, and minor improvement is even possible. This occurs in about 10% of patients, who tend to be older than average at the time of diagnosis.
Progressive-Relapsing MS (PRMS). PRMS is progressive from the start with acute symptom flare-ups, but may have some relapses with continued deterioration between them. It occurs in less than 5% of patients.

Because the natural courses of primary-progressive and progressive-relapsing MS are similar, some experts believe this distinction is unnecessary.

Click the icon to see an image depicting multiple sclerosis.

The Autoimmune Disease Process

Multiple sclerosis is referred to as an autoimmune disease. The general theory for the development of MS is that a genetically damaged immune system is unable to distinguish between virus proteins and the body’s own myelin and so produces antibodies that attack. In other words, the body becomes allergic to itself, a condition known as autoimmunity.

Autoimmunity may develop when the body's immune system is damaged by genetic or environmental factors or both, causing it to attack its own tissues. In the case of MS, the immune system attacks the tissues that make up myelin:

Myelin is made from layers of cell membranes that are produced in the brain and spinal cord by specialized cells called oligodendrocytes. The destruction of this myelin sheath during the disease process is the hallmark for multiple sclerosis.
The myelin coat is distributed in segments along the axons, the long filaments that carry electric impulses away from a nerve cell.
The segments are separated from each other by tiny clusters called nodes of Ranvier, which house channels for sodium ions. These sodium ions are important for boosting the electrical charge required to pass signals from one nerve to another.
As the myelin insulation is destroyed, signals transmitted from nerve cell to nerve cell throughout the central nervous system are disrupted.
Experts once believed that axons themselves were spared during the disease process. Research, however, has shown that many are severed in MS and, in fact, axon destruction appears to start at an early stage in the disease and may be a major cause of its irreversibility.

The body often makes corrective actions to offset the effects of the nerve cell destruction:

For example, researchers have observed an increase in the density of the sodium channels, which carry electric charges. By increasing their numbers, the nerve cells can continue to communicate, in spite of the loss of myelin.
The nerves also retain some capacity to remyelinate (to restore the insulating myelin).

Such processes are probably responsible for the remissions that most patients experience. Unfortunately, the disease process nearly always eventually outpaces these corrective actions.

The Normal Immune Response.

The most important critical immune factors in the disease process are white blood cells called lymphocytes, which consist of T cells and B cells. These cells are the warriors in the immune defense system.
Receptors on T cells acquire the ability to recognize specific molecules called antigens. Antigens are typically proteins from infecting organisms, such as bacteria or viruses, and perceived as a threat to the body.
Once the antigen is identified, specific T cells, called helper T cells, trigger the B cells to release antibodies. These molecules are designed to attach to and destroy the targeted antigen.

Autoimmunity.

Multiple sclerosis, and probably all autoimmune diseases, involves an error in the education of T cells, which makes them unable to distinguish self from non-self.
In multiple sclerosis, the miseducated T cells mistake molecules in the body's own myelin as a foreign antigen. Such targets are referred to as self-antigens.
In response to detection of these self-antigens, the T cells set off the usual cascading immune events, including the release of B lymphocytes, to rid the body of the perceived threat.
The B lymphocytes fire off antibodies as usual, but in this case they are referred to as autoantibodies, because they are attacking antigens that belong to the body's own self.
In MS, the immune system is tricked into targeting self-antigens that are myelin proteins, the fatty insulation covering the nerve fibers. Another autoantibody target may be the oligodendrocytes themselves -- the specialized cells that make up myelin.
To make matters worse, the process perpetuates through a cascading series of events in which the B cells and T cells continue to interact, creating numerous different self-antigens. The attacks continue and, in the process, the original self-antigen is unrecognizable.

Cytokines and the Inflammatory Response. The inflammatory response is the product of an overactive immune system and is a major destructive force in an autoimmune disease.

Once the lymphocytes have launched a response to an antigen, they also release masses of other white blood cells to gather at the injured or infected site.
The major players in this response are white blood cells called leukocytes. Researchers are particularly interested in leukocytes called cytokines. These are small powerful proteins that, in tiny amounts, are indispensable for healing. When they are overproduced, however, which occurs in MS, they play a major role in the destructive process.
Their intensive convergence on the affected area causes it to become inflamed and injurious to the very cells they are designed to protect. Under normal conditions, this inflammatory process is controlled and self-limiting, but in people with autoimmune diseases such as multiple sclerosis, the process persists and damage occurs in the surrounding tissues.

Important cytokines in MS appear to be tumor necrosis factors, interleukin-12, and interferon-gamma. Other cytokines, including interleukin-10 and transforming growth factor beta, may play a protective role and help block inflammatory activity.

The inflammatory response may trigger the disease, but afterward a progressive course takes over that does not appear to be related to inflammation. Experts have found that destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is a major feature of multiple sclerosis. In fact, it may be the major cause of permanent disability that occurs with this disease. Microscopic studies reveal that axons are injured early on as "bystanders" while myelin is being peeled off. As the disease progresses, these weakened and exposed axons degenerate further. Most of the damage occurs early in the disease process and decreases over time, although some destruction can still be observed years and decades afterward. Such evidence is having significant effect on approaches to treatment and research.

Symptoms

Most patients first experience multiple sclerosis as a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis. Much less commonly, the disease is progressive from the start and symptoms are more or less continuous.

Early symptoms may include the following:

Optic neuritis and other problems in the eye. Optic neuritis, which is inflammation of the nerves in the eye, affects over 50% of patients and is the first symptom in about 16% of patients. Symptoms include unclear or doubled vision, usually in one eye. Some people see a shimmering effect. Patients may also experience pain or involuntary jerking or movement of the eye (called nystagmus). In 20% of people with this condition, MS develops within 2 years after the onset. In 45 - 80%, MS develops within 15 years. About 17% of people eventually experience impaired eye movement.
Fatigue. Fatigue is typically worse in the afternoon and may be accompanied by an increase in body temperature. At the onset, this occurs in about 20% of patients, but as the disease progresses, this is a significant symptom in nearly all patients.
Changes in sensations in the arms and legs. Patients can experience heaviness, weakness, or clumsiness in the limbs. Tingling or loss of sensations can also occur, most commonly in the legs. The first symptoms for patients with primary progressive MS often develop slowly in the upper legs.
Muscle weakness in the legs and poor coordination.
Lhermitte’s sign. This is an electrical sensation that runs down the back and into the legs, which is produced by bending the neck forward.
Spasticity. Spasticity is the inability to control muscle tone and leads to spasms and stiffness. It is very common in MS.
Disturbances in the bladder.

In addition to the persistence of early symptoms, some patients experience the following symptoms as the disease progresses:

Imbalance and dizziness.
Tremors.
Facial pain.
Spasm-related symptoms. They include burning, itching, aching, quivering sensations. They usually occur in the extremities and last seconds to minutes.
Speech difficulties.
Difficulty swallowing.
Symptoms in the gastrointestinal, urinary, and genital tracts. Possible sexual dysfunction and loss of bowel and bladder control in severe cases.
Emotional mood swings. Depression is very common. About 10% of patients suffer from psychosis (manic depression and paranoia). About 5% of patients with severe MS experience uncontrolled and extreme mood swings called the laughing/weeping syndrome.
Problems in concentration and memory.
Hearing loss.

Infections. Viral infections have long been known to worsen MS symptoms. An important 2006 study indicated that bacterial infections can also trigger MS relapses. In the study, relapses appeared within 2 weeks of a viral or bacterial infection.

Heat. Heat, whether generated by ambient temperature, infection, or physical activity, worsens MS symptoms in about 60% of patients.

Stress. There is a strong correlation between severe stress and exacerbation of MS symptoms. For example, in one study, 85% of instances of MS exacerbations were associated with stressful events that occurred within an average of 14 days before the episode. Stress is not a cause of MS, however.

Trauma. Some experts believe that injury (trauma) to the head, neck, or upper back may trigger new or recurrent symptoms by disrupting the blood-brain barrier and allowing immunological attacks on the brain. This is a highly controversial theory, however, with very little supporting evidence.

Causes

The cause, or causes, of multiple sclerosis remains a mystery. Genetic factors certainly play a role in MS. No single gene, however, is likely to be responsible for causing MS. Rather, the current theory is that the disease occurs in people with a genetic susceptibility who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack (a self-attack) on myelin and axons. Still, a number of disease patterns have been observed in patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Some research suggests that all autoimmune diseases are basically due to the same genetic error. A 2001 study found, for example, that the T cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders. Nor, why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

Genetic factors probably play some role in making a person susceptible to the disease process leading to multiple sclerosis. In particular, abnormalities in the human leukocyte antigen (HLA) region located on chromosome 6 appear to be more prevalent among people with MS. Researchers theorize, however, that a combination of genes (not a single gene) is implicated in the development of MS, and the risk for someone inheriting all of these genetic factors is less than 5%. Advanced techniques called microarray technologies are now making it possible to scan hundreds of genes and identify those most likely to be contributors to MS. Genetic research may also pave the way for the development of new drugs to treat this disease. For example, researchers have recently identified the Olig1 gene as a key regulator in repairing damaged myelin-producing cells.

Infectious organisms, most likely viruses, are the top suspects for triggering the autoimmune response in people genetically susceptible to MS. There are a number of reasons for this belief:

The geographical distribution of the disease. The number of MS cases increases the further one gets from the equator in either direction.
Multiple sclerosis clusters. Four separate clusters of multiple sclerosis outbreaks occurred between 1943 - 1989 in the Faroe Islands, located between Iceland and Scandinavia. During World War II, this region was occupied by British troops. The incidence of MS increased each year for 20 years after the war, leading some researchers to think that the troops might have brought with them some disease-causing organism. In fact, one theory suggests that these findings offer evidence that MS is a sexually transmitted infection that occurs during adolescence. For example, the disease clusters observed in the Faroe Islands could be related to high sexual activity between the troops and local young women. A high incidence of MS is found in countries with a high degree of sexual permissiveness. MS is very rare in traditional cultures, but increases in people from these regions when they immigrate to industrialized Western nations.
Viral similarity to myelin. Some viruses are strikingly similar to the myelin protein and may therefore cause confusion in the immune system, causing the T cells to continue to attack their own protein rather than the viral antigen. More than one antigen may be involved; some may trigger the disease, and others may keep the process going.

Infectious Organisms Under Suspicion. Although many infectious microorganisms have been investigated, no one organism has emerged as a proven trigger. It is possible that different patients may be affected by different organisms, and that infections cause some, but not all, cases of MS. Organisms that are at the top of the suspect list are those that can affect the central nervous system. The following are three primary suspects:

HHV-6. Herpesvirus 6 (a form of herpesvirus that causes roseola, a benign disease in children) is also known to cause encephalitis (brain inflammation) in patients with impaired immune systems. A number of studies have reported higher than normal rates of HHV-6 infection in patients, and some experts believe that may be important in MS. Other experts argue, however, that nearly everyone harbors this virus and there is still no evidence of a causal relationship. Other herpes viruses can also infect brain cells. They include herpes simplex 1 and 2 (the causes of oral and genital herpes), varicella-zoster virus (the cause of chicken pox and shingles), and cytomegalovirus.
Epstein-Barr virus (EBV). Evidence suggests an association between EBV, the cause of mononucleosis, and MS. EBV is an extremely common virus and another member of the herpes virus family. Nearly all people have been exposed to EBV. However, researchers have discovered that people who are especially sensitive to the virus and have unusually high levels of EBV antibodies may have a greater risk of developing MS. Scientists are still uncertain if EBV is a cause of MS. EBV has also been linked to other autoimmune diseases such as lupus.
Chlamydia Pneumoniae. This atypical bacterium has been associated with persistent inflammation. A few studies have reported significantly higher rates of previous Chlamydia infection in patients with MS than in individuals without MS. An important group of 2000 studies reported no connection at all between Chlamydia and MS, and any experts now believe there is no strong evidence linking the microbe to MS. It is still possible, however, that the infection, which can cause widespread inflammation, plays a role early in the course of the disease in some individuals.

Other viruses that have been investigated include measles virus, adenovirus, and the retroviruses (HIV, HTLV-I, and HTLV-II), but none have emerged as having any importance.

Note on Vaccinations: Concerns about a link between the hepatitis B vaccine and MS led France to halt a major vaccination program in 1998. Subsequent research investigating whether the hepatitis B vaccine is indeed associated with an increased risk of MS has yielded mixed results. It appears that the vaccine would be, at most, a contributing -- but not the sole -- factor in MS development. At present, the evidence has not warranted any change in American immunization policies. Research has ruled out a link between any other vaccinations, such as or influenza or tetanus, and relapses of MS.

Risk Factors

An estimated 400,000 Americans and 2.5 million people worldwide suffer from MS.

Age. Onset occurs between the ages of 20 - 40 years in 70% of patients with the average age being 30 and the peak incidence occurring in the mid-twenties. The disease can still occur in both younger and older individuals. It rarely develops before age 15 or after age 60, however.

Gender. MS is more common among women than men. The gender gap is strongest among people who develop MS at a younger age. According to research presented at the 2007 American Academy of Neurology annual conference, the ratio between women to men has been growing. Researchers found that in the 1940s, the ratio of women to men with MS was 2 to 1. By 2000, the ratio had grown to 4 to 1. However, some research indicates that men may be more disabled by the disease than women.

Ethnicity. Multiple sclerosis occurs worldwide but is most common in Caucasian people of northern European origin, especially those of Scottish descent. It is extremely rare among Asians, Africans, and Native Americans. Specific groups (gypsies, Eskimos, Bantus) have never reported a case. While the risk of MS for African-Americans is around half of that for Caucasians, a recent study suggested that African-Americans are more likely to develop a more aggressive form of the disease and to suffer impaired mobility.

Geography. The risk for MS is higher in different regions of the world. In general, MS is more prevalent in temperate regions than in the tropics. Specifically, prevalence is highest in northern and central Europe (except northern Scandinavia), Italy, southern Australia, and northern regions of North America. Middle-risk areas include southern Europe (except Italy), southern US, northern Australia, and northern Scandinavia. Low-risk areas include parts of Africa and Asia, the Caribbean, Mexico, and possibly northern South America. It is unclear whether this pattern is attributable to environmental factors, genetics, or both.

Family History. A family history of the disease also puts people at risk for MS, although the risk for someone inheriting all the genetic factors contributing to MS is only about 2 - 4%. A 2007 study indicated that family members who have MS tend to develop the disease at around the same age. However, family history does not predict whether one family member will experience the same disease severity as another family member.

Cow's Milk During Early Infancy. Breast milk contains factors that may help regulate the immune response, and there is some evidence that infants fed only on cow's milk may have a higher risk for either diabetes type 1 (another type of autoimmune disease) or multiple sclerosis later in life. Studies on national differences in diabetes suggest that the risk may vary with different milk proteins, suggesting that not all cow's milk is the same and that some proteins carry higher risks than others.

The Hygiene Theory: Early Infections as Protection Against Allergies and Autoimmune Diseases. Over the past decades, there has been a dramatic increase in asthma, allergies, and autoimmune diseases, such as multiple sclerosis, Crohn's disease, and type 1 diabetes. One theory blames this rise on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. Studies supporting this have observed a higher incidence of allergies and autoimmune diseases, including MS, among populations with good hygiene and in animals that have been raised in a germ-free environment. The basic theory rests on the idea that early infections stimulate production of specific immune factors that protect against allergies and autoimmune diseases. The exact mechanisms of these effects are as yet unknown.

Vitamin D. Higher blood levels of vitamin D have been associated with a lower risk for MS, at least among Caucasians. (Studies have not shown that vitamin D has a protective effect for other racial groups.) However, there is not yet enough evidence to indicate that taking vitamin D supplements can help prevent MS.

Exposure to Sunlight. In a 2003 study, higher exposure to sunlight during childhood and early adolescence was associated with a lower risk for MS, perhaps because UV radiation produces higher levels of vitamin D, which has been associated with protection against MS. The effect of sunlight during winter seemed to be more protective than summer light. Unfortunately, higher exposure to sunlight also coincides with a higher risk for skin cancer, which is far more common than MS.

Estrogen and Oral Contraceptives. Higher estrogen levels may temporarily lower the risk of developing multiple sclerosis. Studies indicate that oral contraceptives (which contain estrogen) and pregnancy delay the onset of multiple sclerosis. The risk for a first clinical attack increases, however, in the 6 months after a woman gives birth.

Complications

Multiple sclerosis is not a fatal disease. Some data suggest that it shortens the average life span by only about 6 or 7 years. Still, in about half of MS cases, patients die of complications of the disease, and the disease has significant negative emotional and physical consequences. Suicide rates among patients with MS are higher than average.

The severity of the disease varies widely from patient to patient and is unpredictable. About 20% of patients remain asymptomatic or become only mildly symptomatic after an initial clinical event. Another 20% experience a rapidly progressive condition. Most patients, however, will experience some degree of progression.

Women tend to have a better outlook than men. Factors the determine a higher risk for a severe condition include:

Age over 40 years at the time of onset of symptoms
Initial symptoms that affect motor control, mental functioning, or urinary control, or initial symptoms affect multiple regions
Attacks in the first years that are frequent or interval between the first two attacks is short
Incomplete remissions
Rapid progression to disability
MS that is progressive from the beginning or becomes progressive shortly after the onset

Doctors and researchers often use a scale called the Kurtzke Disability Status Scale to assess and predict future disability. The system uses a score of 1 to 10 to rate the degree of walking disability. Experts have used the scale to attempt to predict average times for progression from one stage to the next depending on whether patients have relapsing-remitting or chronic progressive MS.


Score	Disability Description	Relapsing-Remitting MS: Average time until onset of symptoms*	Chronic Progressive MS: Average time until onset of symptoms*
1	No disability and minimal neurologic symptoms.	11.4 years from Score 1 to Score 4	0 years from Score 1 to Score 4
2	Minimal disability in one or two functional areas. Slight weakness or stiffness, mild walking impairment or visual disturbances
3	Moderate disability in one functional area, such as vision or the urinary tract, and possibly more than one minimal disability in several others. Either a part of one of the limbs or a whole side can be partially paralyzed. May stagger at times.
4	Disability is relatively severe but there is full ability to walk without aid. Patients are self-sufficient and can be active 12 hours a day and carry on normal activities. Can walk without aid or rest for 300 to 500 meters.
5	Disability is severe enough to impair or even preclude a full day's activities. Able to walk unaided and without rest for 100 to 200 meters.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
6	Can walk unaided for about 100 meters only with assistance or devices, such as two canes, crutches, or braces.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
7	Mostly restricted to wheelchair, although can manage the wheelchair and leave it unassisted. Can walk with aids no further than about five meters.	33.1 years from Score 1 to Score 7	13.4 years form Score 1 to Score 7
8	Mostly restricted to wheelchair or even bed, but still has effective use of arms remains and able to perform many self-care functions.	(Data not available)	(Data not available)
9	Bedridden. Patient can communicate or eat.
10	Fatality occurs from complications.
* Data taken from Relapses and Progression of Disability in Multiple Sclerosis, The New England Journal of Medicine, November 16, 2000, Vol. 343, No. 20

Because the effects of nerve injury are widespread, complications can be very severe and affect all parts of the body. Although not all patients experience all of the following problems, any of them can negatively impair quality of life.

Fatigue. Fatigue is one of the most common and debilitating MS symptoms and affects at least two-thirds of patients with MS. Fatigue specifically attributed to MS and not to other causes is defined as abnormal fatigue that lasts at least half of the time or more than 6 weeks. It causes a general lack of energy that significantly limits daily functioning regardless of any neurologic symptoms or specific muscle weaknesses. Up to 40% of patients describe fatigue as the most disabling MS symptom, which is higher than weakness, spasticity, motor control, or bowel or urinary problems. Many conditions that are common in MS (sleep disorders, depression, hypersensitivity to sensation, hypothyroidism, medications, heat) may contribute to fatigue. None fully explain the consistent presence or severity of this problem in MS. Researchers using imaging techniques have identified possible changes in part of the brain in MS that may play a role in the fatigue of MS.

Loss of Mobility and Spasticity. Nearly every patient loses some mobility, which may take the form of less or impaired motor control, muscle weakness, impaired balance, and, importantly, spasticity. Spasticity is one of the primary symptoms of MS. It is characterized by weakness, loss of dexterity, and the inability to control specific movements. It is usually more severe in the legs and torso. (Ironically, mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking.) Mobility can be affected by many non-physical factors, including mental well-being, social networks, fatigue, and even the weather.

Pain. About two-thirds of patients experience pain at some point during the course of the disease, and 40% are never pain free. MS causes many pain syndromes; some are acute while others are chronic. Some worsen with age and disease progression. Pain syndromes associated with MS are trigeminal (facial) pain, powerful spasms and cramps, optic neuritis (pain in the eye), pressure pain, stiffened joints, and a variety of sensations, including feelings of itching, burning, and shooting pain.

Bowel Dysfunction. Bowel dysfunction, which can include constipation or fecal incontinence, is a serious problem for many patients. Constipation may be caused by the disorder itself or by medications used to treat spasms or other symptoms.

Sexual Dysfunction. Sexual dysfunction is a common problem, occurring in over 70% of patients. Men are likely to have impotence and women, problems with vaginal lubrication. It appears to be highly associated with urinary dysfunction.

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal function. When there is CNS damage, the function of these organs and tissues may be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems and sexual dysfunction.

Urinary Dysfunction. Urinary problems from bladder dysfunction occur in two-thirds of patients. Some patients have difficulties in urinating at will, called urinary retention. Often it takes the form of urge incontinence (also called hyperactive or irritable bladder). People with urge incontinence need to urinate frequently or are unable to reach the bathroom before leakage. In such cases, the bladder is overactive. Complications in the urinary tract also produce a high rate of urinary tract infections.

Difficulty Swallowing. A third to a half of patients experience difficulty in chewing or swallowing, problems that may be caused or made worse by many MS medications.

Speech and Hearing Problems. Problems in speech may occur because of difficulty in controlling the quality of the voice and articulating words. (Problems with language itself, however, are very rare in MS.) Hearing problems also occur in MS and may affect speech.

Problems in the Lungs. As the muscles that control breathing weaken, the ability to cough is impaired and the patient is at higher risk for pneumonia and other complications in the lungs.

Osteoporosis. Osteoporosis (loss of bone density) and subsequent fractures are common and under-recognized problems among patients. Osteoporosis is caused and worsened by immobility and by some MS medications. Fractures caused by falls can be far more serious in patients than in the normal population, leading to problems, including deconditioning or even inability to walk, obstruction of the intestines (from pain-relieving medications), and respiratory complications.

Cognitive problems, such as having trouble concentrating and solving problems, affect about half of patients. More people with MS leave work because of such cognitive difficulties than because of physical problems, according to a 2000 study. In about 10% of cases, mental dysfunction may be severe and resemble dementia. The severity of such mental changes appears to be associated with the degree of loss of brain tissue. This offers another argument for early treatment as interferon medications may improve these symptoms.

Between 40 - 60% of patients suffer from depression at some point over the course of the illness, and studies have reported risks for suicide ranging from 3 - 15%. Some evidence suggests that depression in multiple sclerosis is not only due to the social and psychologic impact of MS but also to the disease process itself. Depression may have biologic effects, such as increasing production of inflammatory cytokines, that could exacerbate the disease itself. Doctors should assess patients for depression, even if there are no obvious signs of it. The risk for suicide may be present even in patients who are not obviously depressed. People at highest risk for suicide are those who live alone, those with a history of an emotional disorder (depression, anxiety, alcohol abuse), a family history of mental illness, and people with high social stress.

Diagnosis

Multiple sclerosis is characterized by recurring neurologic episodes that are due to multiple lesions (injured areas) in different locations in the central nervous system. The diagnostic challenges in multiple sclerosis are two-fold:

Making an initial diagnosis as early as possible in order to slow down the disease progression. Most patients first seek medical help after an initial inflammatory event (known as a clinically isolated syndrome) originating from demyelination in the eye, the spinal cord, or the brain. About 30% of these individuals will develop progressive MS within the year. At this time, however, experts cannot predict who among these patients are at highest risk for rapid progression.
Predicting the severity of the disease. Once MS has been diagnosed, the pattern of the disease is uncertain. It can be very benign to rapidly progressive and severe. Magnetic resonance imaging (MRI) is able to detect lesions in the brain indicating MS. But, the severity of the disease does not appear related to the number of lesions, the rate of their appearance, or their location. Researchers are hoping to identify some biologic marker, possibly certain antibodies, that will enable doctors to accurately determine the onset and severity of the problem once a diagnosis has been made.

The McDonald Criteria. There is no single test that can accurately diagnose MS, and a number of other conditions may mimic its symptoms. Some doctors use a set of factors, called the McDonald criteria, for diagnosing multiple sclerosis in early stages. The criteria include the presence of specific symptoms, spinal fluid evaluation, and magnetic resonance imaging techniques for detecting lesions within the central nervous system and tracking them over time. The criteria show high reliability in identifying MS in patients with a variety of disease stages or states, including having only one episode, a typical relapsing-remitting course, or a slow insidious progression without clear attacks or remissions. Depending on the MRI and other findings, the patient is then categorized as having MS, possible MS, or no MS.

The symptoms of MS are similar to a number of other diseases, which must be ruled out. These include stroke, alcoholism, emotional disorders, Lyme disease, chronic fatigue syndrome, fibromyalgia, AIDS, and certain other autoimmune disorders (hypothyroidism, scleroderma, Sjögren syndrome, and systemic lupus erythematosus).

Doctors and investigators generally use a test called the Expanded Disability Status Scale (EDSS) to rate the severity of symptoms. It is also used after a diagnosis to gauge the status of the disease, and score the effectiveness of treatments. The scale ranges from 0 to 10 with higher scores indicating more severe symptoms. These are subjective ratings that require doctor observation skills.

Objections to the use of the EDSS are that it assesses only limp and walking problems and does not assess other important complications, including fatigue, sexual function, and mental function.

No reliable single laboratory procedure or test can establish the diagnosis of multiple sclerosis. Several are necessary before a diagnosis can be made.

Analysis of Cerebrospinal Fluid (CFS). Obtaining a sample of spinal fluid requires a lumbar puncture, or spinal tap. Testing spinal fluid is becoming increasingly important for detecting abnormal proteins, tiny fragments of myelin, or specific white blood cells that can help in making a diagnosis. For example, high levels of the immunoglobulin IgG is useful for making a diagnosis and may be a marker for disease progression. (Immunoglobulins are protein chains that are part of the immune system.)

A lumbar puncture, or spinal tap, is a procedure to collect cerebrospinal fluid to check for the presence of disease or injury. A spinal needle is inserted, usually between the 3rd and 4th lumbar vertebrae in the lower spine. Once the needle is properly positioned in the subarachnoid space (the space between the spinal cord and its covering, the meninges), pressures can be measured and fluid can be collected for testing.

Evoked Potential (EP) Test. This is a simple and painless electrical test of nerve function that assesses how long it takes nerve impulses from the eye, ear, or skin to reach the brain.

Magnetic resonance imaging (MRI) scans are important diagnostic tools in MS and are used for diagnosing multiple sclerosis, tracking changes over time, and helping to determine treatment effectiveness.

Click the icon to see an image of a brain MRI.

Making a Diagnosis and Tracking the Disease. Magnetic resonance imaging (MRI) scans can detect bright patches that indicate injured tissue (lesions) caused by MS. Such lesions may also indicate other conditions, such as infections, migraines, or clots. Importantly, a very sensitive MRI technique using enhancement by a contrast material called gadolinium can indicate recent activity by showing if the blood-brain barrier has been broken down (the first step in the development of MS lesions). Detecting lesions and treating MS early in the disease process may help reduce progression. Many experts therefore now advocate performing a brain MRI as soon as symptoms appear.

Once diagnosed, periodic follow-up MRIs can be used to track the disease and effectiveness of treatments in two ways:

By distinguishing new lesions from old ones
Revealing increasing or decreasing numbers of lesions within the central nervous system over time

Unfortunately, neither the rate nor the number of new or growing lesions necessarily predicts whether symptoms will worsen or if the patient will develop secondary progressive MS.

Measuring Atrophy in Brain and Spinal Cord. As myelin, axons, oligodendrocytes, and neurons are destroyed, the brain begins to shrink. Processing MRI images to determine brain volume may be a useful way to monitor progression and treatment effects. MRI can also detect shrinkage in the spinal cord, which is proving to be a very strong marker of disease progression. A variation of MRI, magnetic resonance spectroscopy (MRS), provides information on the biochemistry of the brain, and may be particularly helpful in detecting this destructive aspect of MS.

Detecting Black Holes.Severe disease progression can be gauged by the presence of so-called "black holes.” These are lesions in the brain that emit very low signals on an MRI scan. Some evidence suggests that they may represent iron deposits in the brain.

Researchers are continuously searching for biologic markers that might help make an accurate diagnosis, predict outcome, or both. Promising markers are antibodies that target two key protein components of myelin: Myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). If future studies confirm the predictive value of these antibodies, scientists may be able to develop a blood test for MOG and MBP.

Treatment

Patients diagnosed with multiple sclerosis face great uncertainty, since the course of the illness varies so widely among patients. Experts recommend a multidisciplinary approach to the disease, which might involve a neurologist, a nurse or social worker expert in MS, and possibly a specialist in mental health (since depression is so common and the suicide rate is higher than average).

Evidence now strongly suggests that the most destructive changes from multiple sclerosis in the brain occur very early on in the disease process -- and may cause considerable damage even before symptoms begin.

Many experts are now urging treatment after a first episode of relapsing MS (a clinically isolated syndrome) using medication called disease-modifying drugs. They include three interferons -- IFN1b (Betaseron) and IFN1a (Avonex, Rebif) -- and glatiramer (Copaxone). These drugs are all effective and may help slow down or even prevent progression in some patients. Definitive studies comparing them are ongoing.

The best current approach is to use specific findings from advanced MRI techniques to help determine which patients are at highest risk for progression and would be likely candidates for early treatment with disease modifying drugs.

Interferons and other disease-modifying drugs can have significant side effects and are expensive. Furthermore, a significant number of patients have a mild course that can be managed with less toxic drugs. Nevertheless, strong evidence suggests that delaying treatment in most patients increases the risk for severe disability.

Corticosteroids are the standard drugs for treating an acute relapse and hastening recovery. Typically, intravenous methylprednisolone (IVMP) is given once a day for 3 days. Sometimes this is followed by oral prednisolone for a few days.

Disease Modifying Drugs. Since the introduction of disease modifying drugs -- interferons beta (Betaseron) and alpha (Avonex, Rebif) and glatiramer (Copaxone) -- relapsing-remitting multiple sclerosis is now considered a treatable disease. In patients with very active MS, some experts start with Betaseron or Rebif. For patients with possible or probable MS, they begin with Avonex. This drug is slightly less effective than Rebif and Betaseron but has fewer side effects. Copaxone is also a reasonable choice for early mild MS. It appears to have the fewest side effects, longer relapse-free rates than interferons, and its benefits persist for years.

The newest drug, the monoclonal antibody natalizumab (Tysabri), was approved in November 2004 for treatment of relapsing forms of MS. The FDA withdrew it from the market, however, in February 2005 following reports of serious neurological events. In June 2006, the FDA allowed natalizumab back on the market but with special restrictions (see Drug Treatment section).

Other Approaches. Some research has reported benefits from the use of pulsed administration of intravenous methylprednisolone (IVMP) or intravenous immunoglobulin, although there is not enough evidence for either approach to recommend them as first-line choices. Other drugs showing promise include azathioprine (an immunosuppressant) and laquinimod (an oral immune-modulating drug).

Treating Secondary Progressive Multiple Sclerosis (SPMS). Interferons and other standard treatments for relapsing-remitting MS may be helpful for patients with SPMS who are still experiencing relapses. It is not clear if they help those whose condition has become continuously progressive.

Mitoxantrone (Novantrone) was the first drug approved for SPMS. The drug is an immunosuppressant and is proving to delay relapse and progression. Side effects, however, can be serious in some cases. Some experts recommend using mitoxantrone when evidence suggests progression to SPMS, and continuing the interferons Betaseron or Rebif for maintenance.

Other immunosuppressants, such as cyclophosphamide, methotrexate, and cladribine, may help some patients with SPMS. They can have very toxic side effects, however, and there must be clear treatment indications for patients who take these drugs.

Treating Primary Progressive Multiple Sclerosis. No treatments have been proven yet to slow progressive multiple sclerosis. Studies using interferons and glatiramer are under way.

A number of treatments are available for managing symptoms and complications.

Drug Treatment

Corticosteroids (commonly called steroids) are mainstay treatments for acute relapses patients with relapse-remitting MS. High-dose methylprednisolone given intravenously (IVMP) is typically administered for major relapse, often followed by oral prednisone for a few days. Steroids reduce inflammation in the central nervous system and may help suppress the immune system's attack on myelin and even improve electrical conduction.

Steroids, in general, do not improve the long-term course of the disease and can lose effectiveness if overused. They are not generally used for maintenance therapy. Some research, however, is reporting benefits from the use of pulsed administration of intravenous methylprednisolone. Such an approach typically administers the steroid daily for 5 days every 4 months for 3 years, then every 6 months for 2 years. Some research suggests that this approach might reduce destruction in central nervous system, although more evidence is needed before it can be recommended. They can also have considerable adverse effects when used over time.

Side Effects. Side effects of long-term use of steroids include weight gain and facial fullness, hypertension, diabetes, osteoporosis, cataracts, intestinal bleeding, and increased susceptibility to infections. In addition, side effects of steroids on the central nervous system (sleeplessness, memory loss, anxiety, and depression) can be particular problems for patients. It is extremely important to taper withdrawal very carefully after continuously taking steroids for a prolonged period of time. This gives the body time to recover its own ability to produce natural steroids. A serious condition known as adrenal insufficiency can otherwise develop.

Interferons (so-called because they “interfere” with viral replication) both suppress important inflammatory factors in the immune system and have anti-viral properties. Interferons specifically block immune factors known as class II MHC molecules, which are associated with the attack on myelin and the breach in the blood-brain barrier that allows the destructive T cells to pass through.

Specific Interferons Used for MS. Interferon drugs used for MS are IFN1b (Betaseron) and IFN1a (Avonex, Rebif). They are now the treatments of choice for relapsing-remitting MS. Expert organizations urge that they be used early in the course of the disease and continued indefinitely, unless they produce no benefits or have severe side effects.

Successes and Drawbacks. Interferons can reduce flare-ups overall by 30% and have an even greater effect on reducing major relapses. Disease activity, as measured by MRI scanning, is reduced by over 80%. They appear to be about equal in reducing disability. To date, only Avonex has demonstrated slowing progression of mental impairment. It also appears to be better tolerated than other interferons. Studies on their effects on quality of life are limited. None of the interferons are a cure, in any case, and when the drug is discontinued, disease activity may increase. All of these drugs need to be injected. (Oral forms are under investigation.)

Side Effects and Complications. Side effects include:

Pain at the injection site. Many patients taking Betaseron complain of severe pain at the injection site caused by damaged tissue. Experts recommend taking acetaminophen (Tylenol) before the injection and then every 6 hours after each injection for 24 hours during the first 6 months of treatment.
Skin injury at the injection site. Black dead tissue may form around the site, and many patients taking Betaseron have reported severe skin eruptions. These skin injuries heal after the drug is withdrawn, but scarring can occur. This side effect is least severe with Avonex, followed by Rebif.
Other physical side effects. Both drugs cause flu-like symptoms, nausea, vomiting, headaches, and dizziness. Such side effects usually fade after 2 - 3 months.
Depression. Early studies associated taking interferon with a higher risk for depression during the first 2 - 6 months following initial therapy. More recent studies, however, have reported no greater risk for depression in patients taking any of these drugs. MS itself, in any case, is highly associated with depression.
Thyroid abnormalities. Interferon has been associated with autoimmune thyroiditis, a cause of hypothyroidism. Some experts recommend monitoring for thyroid function, particularly in the first year and in those with a history of thyroid problems. If there is no evidence of the condition during that period, the risk for its occurrence appears to be very low.
Liver damage. Interferon may cause liver damage and, in rare cases, liver failure. Patients should avoid alcohol and have regular liver function tests while taking this drug

Neutralizing Antibodies That Reduce Effectiveness. Over time, people taking interferons develop antibodies to the drugs, some of which can neutralize their effects. The risk for neutralizing antibodies (NAbs) increases with higher doses and greater frequency of use. Interferons injected under the skin (Betaseron, Rebif) are more likely to produce neutralizing antibodies than Avonex, which is injected into a muscle. Patients who experience this, however, often can be effectively treated with an alternative interferon or with glatiramer, which has an extremely low risk, for NAbs. In many cases, after switching drugs, NAb levels decline, and the patient may be able to return to the original interferon.

Glatiramer acetate (Copaxone) is a synthetic molecule that resembles a basic protein found in myelin. It is used as a decoy to trick white blood cells into attacking it instead of myelin. It is approved to help reduce the frequency of relapses in patients with relapse-remitting MS. The best results are in patients in early stages, but the longer patients remain on the drug, the greater the improvement. Benefits have persisted for years. Glatiramer acetate can also help reduce the number of new brain lesions.

Glatiramer acetate is also being studied for its effects in patients with primary progressive MS. A 2007 study indicated that while the drug had little benefit for most patients with this type of MS, it may help slow disease progression and delay disability in men with primary progressive MS.

Side Effects. Side effects occur in about 15% of patients, usually right after the injection. They include pain at the injection site, chest pain, rapid heartbeat, flushing, anxiety, and shortness of breath.

Monoclonal antibodies (MAbs) are drugs that target specific antibodies involved with the immune response. In 2004, natalizumab (Tysabri) became the only MAb approved for treatment of MS. Shortly afterwards, reports emerged of progressive multifocal leukoencephalopathy (PML) occurring among patients who took natalizumab for more than 2 years. PML is a rare neurological disease that can affect people with compromised immune systems. Based on these reports, the FDA suspended marketing of natalizumab in February 2005 and recommended that patients discontinue its use.

In June 2006, the FDA allowed natalizumab to return to the market with certain safety restrictions. Doctors can prescribe the drug only to patients who have failed to respond to or who cannot tolerate other MS treatments. Natalizumab can only be taken alone, not in combination with other immune-modifying drugs. Patients who take natalizumab must enroll in a special program called TOUCH, which is run by the drug’s manufacturer. Patients need to get magnetic resonance imaging (MRI) brain scans before they begin taking the drug, and they are evaluated regularly during drug treatment to make sure they are not at risk of developing PML. In the year after these restrictions were implemented, no new cases of PML were reported.

Clinical trials indicate that natalizumab’s benefits may outweigh its risks. Several studies published in 2006 in the New England Journal of Medicine showed that natalizumab, alone or in combination with IFN1a (Avonex) can help prevent disability in patients with multiple sclerosis. Another study suggested that the risk of PML is very low if patients use natalizumab for less than 18 months.

Natalizumab is also being studied for treating complications associated with MS. In a 2007 study, natalizumab helped reduce vision loss in patients with relapsing MS. Vision loss is one of the most common symptoms associated with MS.

Other MAbs under investigation for MS include daclizumab (Zenapax), alemtuzumab (Campath), and rituximab (Rituxan). Results from a 2005 phase II trial for alemtuzumab indicated that the drug helped prevent relapse but also caused serious side effects. Patients who took the drug had a high risk for developing a serious bleeding disorder caused by a low blood platelet count. Daclizumab is currently in phase II trials as is rituximab. Unlike other MAbs, which affect T cells, rituximab targets and depletes B cells. In several studies presented at the 2007 meeting of the American Academy of Neurology, rituximab showed promising results in reducing relapse frequency and number of brain lesions in patients with relapse-remitting MS.

Intravenous immunoglobulin treatments are monthly infusions of natural antibodies. They appear to have some modest benefits for relapsing-remitting MS. Studies suggests that intravenous immunoglobulin reduces relapse rates and occurrences of new lesions and slows disease progression in relapsing-remitting MS. It does not appear to reduce disability. It is extremely expensive and does not appear to have any benefits for patients with secondary progressive MS.

Many drugs being investigated for chronic progressive multiple sclerosis are immunosuppressants, which block certain factors in the immune system that contribute to the inflammatory process. Each of these drugs can produce serious side effects, including susceptibility to infection. Evidence on benefits is uncertain, mainly because of high toxicity or study limitations. Still, some immunosuppressants may help certain patients with severe MS. Among immunosuppressant drugs or procedures that have been investigated with little or no obvious benefits or unacceptably high side effects are total lymphoid irradiation, sulfasalazine, cyclosporine, acyclovir, and oral bovine myelin.

Mitoxantrone. Mitoxantrone (Novantrone) was the first drug approved specifically for secondary progressive MS. Studies suggest that it may help reduce progression and relapse rates. Cumulative doses can have toxic effects on the heart, however, so the drug is only used for a limited period. Mitoxantrone is also being studied in combination with glatiramer acetate. In one preliminary study, initial treatment with mitoxantrone, followed by maintenance treatment with glatirimer acetate, helped reduce relapses for up to 5 years.

Methotrexate. In some patients, low doses of the immunosuppressant methotrexate may slow the course of chronic-progressive MS, particularly in those with secondary progressive MS. To date, studies have found beneficial effects only on the upper body, however. Although this drug, like all immunosuppressants, can have toxic side effects, it may be taken in low doses for MS and so side effects are generally minimal.

Cyclophosphamide. Cyclophosphamide (Cytoxan) blocks cell growth and also suppresses the immune system. Some studies, but not all, have reported benefits for patients with chronic progressive MS. Small studies suggest that monthly intravenous administration or a combination with interferon-beta may help some patients with rapidly deteriorating MS. Cyclophosphamide has many side effects, including hair loss, nausea, vomiting, infertility, lung scarring, and blood abnormalities, and should be used for patients who do not respond to methotrexate.

Azathioprine. Azathioprine (Imuran) is designed to suppress the immune system and reduce the number of cells attacking the CNS myelin. It is used with or without steroids and is sometimes used as an alternative to patients with relapsing-remitting MS who do not respond to either interferon beta or glatiramer acetate. One study reported that 40% of patients had not experienced a relapse after taking the drug for 3 years, although others report only modest benefits. The drug has no effect on progression of disability.

Cladribine. Cladribine (Leustatin) may be effective in delaying progression in patients with chronic progressive MS. It has no significant effect on relapsing-remitting MS.

A number of treatments are under investigation that may prove to be helpful for multiple sclerosis. Those discussed below are only some of them.

Immune-Modulating Drugs. Most MS drugs are injected, but researchers are developing several new drugs that can be taken by mouth. Four of the most promising candidates are cladibrine (Mylinax), fingolimod (FTY720), teriflunomide, and fumarate (BG00012). In late-stage clinical trials, these drugs have shown positive results in the treatment of relapse-remitting MS.

Sex Hormones. Women with MS have a reduced risk of experiencing relapses during pregnancy, probably because of their high levels of the female sex hormones estrogen and progesterone. Because of this association, researchers have investigated whether oral estrogen therapy (estriol) can help prevent relapses. Some small studies have indicated that estriol treatment may help reduce lesions and disease activity, but the overall evidence is still inconclusive. The male sex hormone testosterone is also being studied as a treatment for men with relapse-remitting MS. A small 2007 pilot study suggested that treatment with testosterone gel is safe and may help improve cognitive function, slow brain degeneration, and increase muscle mass.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis), which may have properties that protect nerve cells. Cannabis has been found to improve pain, mobility, tremor, mood, appetite, fatigue, vision, sexual and urinary function, and memory. In a 2003 study, patients reported less pain and improved mobility (although spasticity itself did not improve). Not all patients respond. The drug may also worsen balance and posture in patients with spasticity. Synthetic versions are being investigated that allow rapid delivery without the unwanted side effects of natural cannabis.

Potassium Channel Blockers. Aminopyridines are potassium-blocking compounds that appear to improve nerve conduction through demyelinated areas. In small, preliminary trials, 4–aminopyridine (also called AP) was associated with mild-to-marked improvement in vision, strength, and coordination and was well tolerated. Beneficial effects, however, lasted only a few hours. A related compound, 3,4–diaminopyridine, or DAP, is being studied for relieving fatigue associated with MS.

Statins. Statins are currently the most important drugs for lowering cholesterol. They are also showing additional possible benefits, including anti-inflammatory and nerve protecting properties, which may help patients with neurologic conditions, including multiple sclerosis.

Plasmapheresis. Plasmapheresis with plasma exchange is a procedure in which blood is removed from the body. Blood cells are separated from plasma (the liquid portion of blood) and mixed with replacement plasma, which is then returned to the body. The replacement plasma is thought to dilute antibodies and other immunologically active substances that may trigger MS. Small studies suggest this procedure may have significant benefits for some patients with severe MS, particularly if they are younger and have an early response to this treatment. Side effects include risk of infection and blood clotting problems.

Stem Cell Transplantation. Investigators are studying the benefits of stem-cell transplantation procedures. Stem cells are produced in the bone marrow and are the early forms for all blood cells in the body (including red, white, and immune cells). Early studies indicate that stem cell transplantation may slow progression, although at this point it is not a cure.

Oligodendrocyte Implants. A newly developed, minimally invasive method to transplant modified oligodendrocyte cells directly into the brain is under investigation. Such cells stimulate nerve and axon growth. If feasible, this approach might be helpful in patients whose MS is not caused by an autoimmune response (where the new cells would be attacked, just as the patient's own cells were).

Other Treatments

Nearly 60% of patients try some form of nontraditional remedies. Research on any benefits is slim, and there may be some danger with many remedies commonly used by patients. The following are a few alternative remedies sometimes used for MS.

Relaxation and Meditation Techniques. Generally harmless, and possibly helpful, nontraditional therapies for MS are relaxation and meditation techniques and Eastern martial art exercises. Such techniques include biofeedback, music therapy, yoga, tai chi, and massage therapy.

Acupuncture. Some patients report benefit from acupuncture, which does carry a very small risk, usually for infection.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Electromagnetic Stimulation. A few centers have studied pulses of weak electromagnetic fields applied to the brain. Very small studies have reported improvement in fatigue, tremors, depression, and other symptoms in patients who were severely affected by MS. In one controlled study, this approach relieved symptoms more effectively than placebo. The effect was small however and more research is needed.

Linoleic Acid. Linoleic acid, commonly known as evening primrose oil, is a polyunsaturated fatty acid believed by some people to be helpful because myelin is composed of fatty acids. No study has proven that it is beneficial, but supplements sold in health food stores do not appear to be harmful.

Oral Enzymes. Oral drugs containing various natural enzymes, including bromelain, trypsin, papain, and rutin, have been used overseas to treat arthritic pain. They appear to reduce inflammation and are also being studied in patients with MS. Such enzymes have been marketed alone and in combinations (Wobenzym, Phlogenzym). In one small study, Phlogenzym was associated with a decline in complications and longer remission. They are not painkillers; any benefits derived from them may take several weeks. As with any natural remedy, there are few clinical studies on these products and no U.S. regulation of quality, safety, or effectiveness.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements

The following warnings are of particular importance for people with multiple sclerosis:

Antioxidants. Some patients use antioxidant vitamins or supplements (A, E, C, Q10, pycnogenol, OPC, grape seed extract), since the destruction in the MS disease process may be partly due to oxidation (chemical damage from particles called oxygen-free radicals). Theoretically, however, antioxidants can trigger T cells and macrophages (inflammatory components of the immune system) and, therefore, may pose some danger to patients. Small studies to date have not found any worsening of the disease from taking vitamin supplements, but patients should be cautious. No vitamins studied for MS, including carotenoids, vitamin C, vitamin E, B12 injections or vitamin D, have been proven to be beneficial.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses. Ginkgo can also interact with high doses of vitamin E, anti-clotting medications, aspirin, and NSAIDs. Large doses have also been known to cause convulsion. Commercial gingko preparations may contain colchicine, a drug that can be harmful in pregnant women and people with kidney or liver problems.

Bee Venom. For years, anecdotal reports have claimed that bee stings relieve some MS symptoms, although a study on mice indicated that it may worsen MS. Bee venom contains many chemicals, some of which can cause severe and sometimes deadly allergic reactions in some people.

Other Remedies. Herbal or natural remedies that supposedly boost the immune system (echinacea, ginseng, garlic, zinc) may worsen MS. Melatonin has been associated with worsening of some autoimmune diseases. Toxic effects have also been reported with herbal remedies such as borage seed oil, chaparral, and comfrey.

Treating the Complications

Fatigue affects at least two-thirds of patients. It is among the most disabling problems in MS and is difficult to treat. Treating any problem (depression, hypothyroidism) that may be causing fatigue is important. Aerobic exercise programs scheduled early in the day have been helpful for patients who can participate. Preventing overheating can improve fatigue.

Modafinil (Provigil, Alertec) is a promising drug that promotes long-lasting wakefulness and is currently used in narcolepsy. Small studies report that it is effective in reducing fatigue and sleepiness, with lower doses (200 mg) being more effective than higher ones. Studies also suggest that the antiviral drug amantadine (Symmetrel) may be helpful.

Managing pain and spasticity in the lower limbs can be difficult. Although many drugs are used to reduce spasticity and lower-limb pain, most studies investigating these drugs have been poorly designed and no treatment has emerged as a front-runner.

Exercise. Mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking. This benefit can be lost with drug treatment. Mild spasticity, then, should be treated with exercises several times a day that improve range of motion.

Drugs Used for Spasticity.

Baclofen (Lioresal) has long been the drug of choice to alleviate more severe spasticity. It is available both orally and infused through an implanted pump. Distressing side effects include confusion, drowsiness, and a rubbery-like sensation in the legs that makes it hard to stand.
Antiseizure medications, such as gabapentin (Neurontin) or levetiracetam (Keppra), may help reduce spasticity without increasing fatigue or impairing concentration. Studies on gabapentin also suggest that it also have other specific benefits for patients, including reducing facial pain and improving vision.
Tizanidine (Zanaflex) is an oral drug that works after one week. In one study, 75% of patients taking tizanidine reported improvement without the leg-muscle weakness experienced using baclofen. The drug does not appear to be any more effective than baclofen, however. Side effects include dizziness, drowsiness, dry mouth, and fatigue. Liver function must be monitored.
Diazepam (Valium) is also used for spasticity and may be particularly useful for patients who also experience anxiety. Drug dependence is the primary problem with diazepam, as well as dizziness, drowsiness, and confusion. The medication should not be used by people who are seriously depressed.
Botulinum toxin (Dysport) injections are being investigated for spasticity in specific regions such as the hip.
Dantrolene (Dantrium) may be an effective alternative for patients who cannot tolerate diazepam or baclofen. Because dantrolene causes muscle weakness, however, it is best suited for either patients who are wheelchair bound but still suffer from spasticity, or for those whose muscles are still strong so that the drug-induced weakness isn't unduly debilitating. It also causes nausea, vomiting, and anorexia, and with high dosages it can cause dangerous liver damage.

Surgery. In very severe cases where medication and exercise are not helpful, surgery may be considered. In such cases, the surgeon cuts the tendons that are involved with spasticity.

Spinal Injections. In very severe cases, administering phenol using spinal injections in the lower back may reduce pain and spasms for some patients with severe conditions. Most patients are not appropriate candidates for this approach.

Other Treatments. Researchers are also investigating non-drug treatments for spasticity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that uses a magnet placed on the scalp to generate a magnetic field that stimulates the cortex of the brain. In a small 2007 study, rTMS showed promise in improving lower-limb spasticity in patients with relapse-remitting MS.

Urge Incontinence. Urge incontinence (the need to urinary frequently) is common in patients. To help reduce social difficulties, patients should not drink fluids before going to places where restrooms are not easily available. When possible, they should urinate every 3 - 4 hours. A number of medications are available for urge incontinence, including anticholinergic drugs, such as propantheline bromine (Pro-Banthine), tolterodine (Detrol), or oxybutynin (Ditropan). Sacral nerve stimulation (InterStim) sends electrical pulses to help retrain nerves in the pelvic area, and is also proving to be helpful. Botulinum toxin injection into the urinary tract muscles is being investigated and may be helpful for incontinence caused by spasticity. [See In-Depth Report #50: Urinary incontinence.]

Urinary Retention. Urinary retention occurs in some patients. Sometimes urination can be stimulated simply by pressing the bladder area with the fist or hand, by tapping against it, or by straining. Drugs being tried with some success for this problem are desmopressin (DDAVP), ordinarily used for bed wetting in children, and maprotiline (Ludiomill), an antidepressant. If medication is ineffective, a catheter may be needed, either one used intermittently by the patient or placed in the urinary tract. Various new surgical procedures that reconstruct the bladder or divert urine flow may be effective in severe cases of bladder dysfunction. Because urinary symptoms usually remain intermittent for years, treatment approaches for bladder dysfunction should be limited to medications and other reversible therapies, for as long as possible.

Urinary Tract Infections. Urinary tract infection is common in patients, and a urinalysis should be performed with any symptom flare-ups, fever, or change in bladder symptoms. Treatment uses appropriate antibiotic regimens. Some evidence suggests that cranberry juice may help prevent infections. [See In-Depth Report #36: Urinary tract infection.]

In addition to maintaining a high-fiber diet and drinking plenty of fluids, bulk fiber such as psyllium (Metamucil), with or without a stool softener, may be needed. Going to the bathroom the same time every day, particularly after a meal and waiting there for a movement, reduces the risk of losing control later in the day. Exercise helps patients avoid becoming dependent on laxatives, enemas, or colonic irrigation, which can eventually slow down the bowel and cause imbalances in electrolytes. Biofeedback techniques may be helpful in some patients with limited multiple sclerosis.

Major tremors can be very distressing and are particularly hard to treat. Carbamazepine and glutethimide have some possible benefits, but in general drug therapy has been disappointing. Weight applied to the affected limb has been beneficial in about 20% of cases. Surgery is very controversial.

Trigeminal neuralgia is facial pain, usually on one side, that can be very severe and may be triggered by an event as mild as a breeze or teeth brushing. If nonprescription painkillers fail to alleviate facial pain, it can be treated with anticonvulsive medications. Carbamazepine (Tegretol) is currently the drug of choice. Carbamazepine is also effective on other types of MS pain and spasm-related symptoms, including itching and aching. Another antiseizure drug, gabapentin (Neurontin), however, may be particularly effective for MS. This drug also appears to improve blurred vision associated with MS and may help spasticity in general.

Other drugs used for this symptom include phenytoin (Dilantin), diazepam (Valium), or pimozide (Orap), and the antidepressant amitriptyline (Elavil). If severe pain persists and interferes with function, some patients elect to have a section of a nerve surgically removed or blocked. This relieves pain but causes numbness. Before patients commit to such a procedure, they should ask the doctor to temporarily block the nerve with an anesthetic in order to experience the effect of numbness before undergoing irreversible surgery.

A small percentage of patients suffer from pseudobulbar affect (uncontrollable laughing or crying). Neurodex is an investigative drug that is showing promise in controlling these symptoms. The drug combines dextromethorphan (an ingredient contained in many cough suppressants) and the enzyme inhibitor quinidine.

Sildenafil (Viagra) may help improve sexual dysfunction in some patients. Corticosteroids, which are sometimes used for other MS symptoms, also improve sexual function. Other treatments are available that might be very beneficial. Patients should not be shy about discussing sexuality with their doctor. [See In-Depth Report # 15: Erectile dysfunction.]

Techniques for helping patients with swallowing problems include using specific head and tongue positions to assist swallowing, and preparing pureed food. Patients may need to work with otolaryngologists (doctors specializing in ear, nose, and throat disorders) to address swallowing problems. Left untreated, swallowing problems can increase a patient's risk of aspiration pneumonia, malnutrition, dehydration, and other problems.

MS is a strong risk factor for osteoporosis. In addition to calcium and vitamin D supplements, a number of drugs are now available to help prevent bone loss and reduce the risk of fractures due to osteoporosis. [See In-Depth Report #18: Osteoporosis.]

Treating Depression. Treating depression may not only improve mood but may also have direct benefits for patients.

Antidepressants known as tricyclics may have specific benefits for MS in addition to managing severe depression. Amitriptyline (Elavil), for example, may be effective in alleviating the extreme mood swings that frequently occur in patients. This “emotional incontinence,” the inability to control emotions, can distress some patients more than physical symptoms. Other tricyclics include desipramine (Norpramin, Pertofrane) and imipramine (Tofranil), which have additional effects that improve bladder symptoms in some patients. These drugs, however, can have severe side effects.
Newer antidepressant drugs, known as SSRIs (serotonin-reuptake inhibitors), which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), may be better tolerated. A study on sertraline suggested that it may also reduce the immune system's inflammatory response.

Stress Reduction and Supportive Measures. Stress can worsen symptoms, and may worsen the disease itself. Reducing stress is an important part of general health maintenance. Studies on methods for reducing stress report improved well-being in patients. A sense of control and connection appears to be extremely important for patients. Relaxation or meditation exercises can be beneficial, although cognitive-behavioral methods may be more effective in these patients. [See In-DepthReport # 31: Stress.]

Support for Caregivers. Many patients require long-term physical, financial, and psychological support from family and friends. The physical and mental health of the caregiver are critical. In one study, caregivers reported that among the most distressing aspects were the psychological impact of MS on the patient and the incurability of the disease. Most caregivers identified the best form of support to be practical help, cooking, cleaning, and better availability of medical and financial advice. Therapeutic help for family members may also be helpful.

Interferon, used to treat MS, may improve mental function. Other medications and therapies may also be helpful. For example, drugs called cholinesterase inhibitors, such as donepezil (Aricept), which are used for Alzheimer's disease, may help improve mental functioning. Vocational programs for the patient may also be helpful. Therapeutic programs for both patients and their families can help them better understand and cope with cognitive weaknesses such as concentration and problem solving.

Lifestyle Changes

People with multiple sclerosis should make every effort to preserve their general health. A healthy diet, sufficient rest, establishing priorities to conserve energy, and developing emotional support networks can all be very helpful.

Some dietary suggestions for patients with MS include:

Drink two quarts of water a day and avoid caffeine-containing beverages, which are actually dehydrating. This helps avoid constipation (although may cause difficulties in patients who also have urge incontinence).
Eat a diet rich in fiber, particularly from whole grains (especially bran, oats, or flax), fruits (particularly prunes), and vegetables.
Low-fat diets have not proven to have much effect on MS but are, in any case, generally healthy.
Fish and fish oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation and some reduction in symptoms in people with various autoimmune conditions. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however. Some experts recommend that people with MS eat three fish meals a week.

Special diets, such as those that are gluten- or yeast-free, have not shown to have any direct effect on the symptoms or course of MS.

Exercise is an important component in managing MS. An active patient with MS is less likely to develop certain complications, such as bladder and bowel dysfunction, osteoporosis, permanent muscle contractions, ulcerations of the skin, or abnormal blood clotting. MS symptoms can temporarily worsen during physical activity, however, so any program must be planned carefully. A health professional should be consulted to determine the best form of physical activity. One study reported that physical rehabilitation for 3 weeks in a hospital setting was significantly more effective in achieving functional independence than home exercise. It is not known if the same benefits can be achieved with a similar program outside the hospital.

Some suggestions include:

Exercise programs must be designed to stimulate working muscles, but at the same time avoid overload and overheating, which can block nerve conduction.
Stretching and range-of-motion exercises are important because they can relieve muscle spasticity.
Pool exercises are particularly helpful. Water supports the body, and cool water dissipates heat.
Specific exercises that strengthen and increase the endurance of muscles that control breathing functions may be helpful. However, it is unclear if such exercises reduce lung complications over the long-term.
Gradually, patients may be able to build up to more complex exercise programs.

Body overheating causes demyelinated nerves to function less efficiently than usual. Although this effect is resolved within a few hours of regaining normal body temperature, active cooling can help reduce fatigue and improve stability. As a result, researchers are studying the effectiveness of cooling suits.

The following measures may be helpful:

Use air conditioners in the summer.
Keep the home slightly cool in winter.
Avoid swimming in heated pools.
A portable helmet that uses cold liquid to cool the head and neck and therefore lower core body temperatures may help MS symptoms during daily activities.

MS symptoms worsen during a cold or the flu, probably because of increased immune system activity. Experts recommend that patients with MS receive a flu shot in the fall. However, experts warn that patients should not take the nasal spray version of the flu vaccine (FluMist Intranasal). Unlike the flu injection vaccine, which uses an inactivated virus, FluMist contains a live virus. Live virus vaccinations may be harmful for people with MS, especially those who take immune-suppressing drugs.

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.msaa.com -- Multiple Sclerosis Association of America
www.nmss.org -- National Multiple Sclerosis Society
www.msfacts.org -- Multiple Sclerosis Foundation
www.www.fda.gov/cder/drug/infopage/natalizumab -- FDA information on natalizumab (Tysabri)
www.myelin.org -- The Myelin Project
www.abledata.com -- National database of assistive devices and rehabilitation equipment

References

Balcer LJ, Galetta SL, Calabresi PA, Confavreux C, Giovannoni G, Havrdova E, et al. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology. 2007 Apr 17;68(16):1299-304.

Boggild M. .Rationale and experience with combination therapies in multiple sclerosis. J Neurol. 2006 Nov;253 Suppl 6:vi45-vi51.

Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27;68(13):1045-50.

Correale J, Fiol M, Gilmore W. The risk of relapses in multiple sclerosis during systemic infections. Neurology. 2006 Aug 22;67(4):652-9. Epub 2006 Jul 26.

Hensiek AE, Seaman SR, Barcellos LF, Oturai A, Eraksoi M, Cocco E, et al. Familial effects on the clinical course of multiple sclerosis. Neurology. 2007 Jan 30;68(5):376-83.

Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40.

Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.

Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64:683-688.

Wolinsky JS, Narayana PA, O'Connor P, Coyle PK, Ford C, Johnson K, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007 Jan;61(1):14-24.

Review Date:
5/26/2007
Reviewed By:
Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

adam.com

Food allergy

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

Overview

Signs and Symptoms
Risk Factors
Diagnosis
Preventive Care
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

About two out of five Americans believe that they are allergic to certain foods. However, fewer than 1% of them have true food allergies. A food allergy occurs when the body's immune system reacts to otherwise harmless substances in certain foods. This is different from a food intolerance, which does not involve the immune system. While most food allergies are mild, in some cases they can cause anaphylactic shock, a serious, sometimes life-threatening reaction. Food allergies affect mostly young children. With the exception of peanut allergy, the majority of children outgrow their food sensitivities.

Signs and Symptoms

Many people who think they have food allergies actually have food intolerances. Symptoms of a true food allergy usually involve the skin and intestines and typically begin just after eating and not longer than 2 hours following ingestion of the particular food. Common symptoms include:

Hives, itching, or eczema
Nausea and vomiting, stomach cramps, indigestion, or diarrhea
Swelling of the eyelids, face, lips, tongue, throat, or other parts of the body (called angioedema)
Wheezing, nasal congestion, or trouble breathing
Lightheadedness, dizziness, or fainting

When the symptoms listed above are extreme, they can be life-threatening. Call a medical emergency response unit if you see the following signs of extreme allergic reaction (anaphylactic shock):

Swelling of the throat and difficulty swallowing
Difficulty breathing
Rapid pulse
Dizziness, lightheadedness, or loss of consciousness
Blue color to the skin and nails

Causes

In most cases, allergies occur when an individual who has a genetic sensitivity to certain allergens is exposed to the substance. Foods frequently responsible for food allergies include:

Shellfish, such as shrimp, crab, and lobster
Tree nuts, including walnuts, almonds, and pecans
Peanuts
Fruits, particularly strawberries, but also melons, pineapple, and other tropical fruits
Tomatoes
Fish
Food additives such as dyes, thickeners, and preservatives. Monosodium glutamate (MSG) is a common food allergy in this category.

Foods that may cause intolerance include:

Wheat and other gluten-containing grains
Cows milk and other dairy products
Corn products

Risk Factors

Family history of allergies increases your risk of having allergies, including food allergies. If both parents have food allergies, you have a 75% chance of having one yourself. If one parent has food allergies, you have a 30 - 40% chance. If neither parent has allergies, you have a 10 - 15% chance.

Excessive exposure to a particular food -- for example, in Japan where rice is a staple, rice is a common food allergen. In Scandinavia, the common allergen is codfish, and in India, chickpeas.

Diagnosis

Your health care provider will take a comprehensive history to find out what symptoms you experience after eating and how soon after eating they occur. Your doctor will also want to know how often you have the reaction and what type of medical treatment you received. Even if your symptoms seem clearly related to a specific food, your doctor may still want to do some tests to be sure that you have a true food allergy and to verify the food or foods responsible for your reaction.

The food causing the allergy can sometimes be identified by the following techniques:

Elimination and re-challenging diet (also called elimination and provocation diet). This technique involves eliminating suspected foods from the diet one at a time until the symptoms disappear. If there is still a question about what may be causing the symptoms, then individual foods are reintroduced one at a time to see if an allergic reaction develops. (Note: this would not be done if the allergic reaction is dangerous or life threatening.) This method is not definitive, but may help narrow the list of suspected foods.
Skin testing. A diluted amount of the food allergen is placed under the skin; if allergic, a raised, red skin lesion will appear, generally within 15 - 20 minutes.
Blood tests (RAST and ELISA). These look for antibodies against the particular food allergens.

Preventive Care

Guidelines from reputable health agencies suggest some steps parents can take to reduce their child's chances of having food and other allergies, although there are no guarantees of success. If either or both parents have a personal or family history of allergy [for example, asthma, eczema, hay fever, perennial allergic rhinitis (allergy to animals, dust mites, or molds)] the following is recommend:

Avoid common allergenic foods, in particular peanuts and tree nuts, during pregnancy and while nursing -- peanut protein, as well as components of cow's milk, eggs, and wheat, are secreted into breast milk
Breast-feed exclusively -- give your baby only breast milk for the first 6 months of life using hypoallergenic formulas to supplement breast-feeding if necessary

Note: Not all studies agree on exclusive breast-feeding. The latest and largest study investigating the relationship between breast-feeding and allergies, particularly asthma, suggests that breast-feeding in the early months of life can prevent allergies until your child is 2 years old.

However, breast-feeding may increase the risk of allergies once your child is older than 2 years. Since delaying foods allows the child's gastrointestinal tract to mature, the following strategies may be helpful:

Delay giving your infant solid food until 6 months of age.
Delay giving your child common allergenic foods as follows: dairy until age 1 year; eggs until age 2 years; peanuts, nuts, and fish until 3 years.
If an allergy develops, carefully avoid the offending food.

Treatment

The goals of treatment are to reduce symptoms and avoid future allergic reactions. Once you are aware of the allergy, the best way to avoid a reaction is by not eating that food. Treatment at the time of a reaction varies according to the severity and type of symptoms. Mild symptoms may go away without treatment. Doctors generally recommend over-the-counter or prescription antihistamines to relieve mild itching, swelling, rash, runny nose, or headache. Soothing skin creams may provide some relief of rashes. Severe allergic reactions (anaphylactic shock) can come on suddenly and accelerate quickly; in this case, emergency treatment is needed. In some instances, survival may depend on an injection of epinephrine (adrenaline). Food allergy sufferers routinely learn to self-administer epinephrine, which may save their life. Avoiding the offending food is the best way to prevent future allergic reactions.

Lifestyle

Avoid offending foods. Read of all package ingredients carefully (many foods are processed with peanuts, eggs, or milk products such as whey). Call ahead when eating out. Take your own food with you on trips.

If you have a history of anaphylactic shock, you should keep a preloaded syringe of epinephrine with you. Your doctor will teach you and a close family member how to use it should the need arise. You should wear a medical bracelet or necklace indicating your particular food allergies.

Medications

Antihistamines are recommended for mild itching, swelling, rash, runny nose, or headache. They are available both by prescription and over the counter in many cold, sinus, and allergy remedies. These include diphenhydramine (Benadryl), cetirizine (Zyrtec), clemastine (Tavist), chlorpheniramine (Chlor Trimeton), desloratadine, fexofenadine (Allegra), hydroxyzine (Atarax), and loratadine (Claritin). Possible side effects include drowsiness, irritability, dry mouth, and heart palpitations.

Skin creams can help soothe rashes.

Epinephrine injection is used to prevent anaphylactic shock. If you have a food allergy that causes such a serious reaction, your doctor will have you carry an injectable epinepherine pen and teach you, and those with whom you spend a lot of time, how to use it in an emergency.

Nutrition and Dietary Supplements

Although you should avoid foods that provoke an allergic reaction, you do not need to restrict variety in your diet. Studies show that the vast majority of people are allergic to only one or two foods. However, you should be aware of the families of foods to which you are allergic. For example, if you are allergic to walnuts, you may also be allergic to pecans and almonds. An allergy to shrimp may also indicate an allergy to crab.

Following these nutritional tips may help reduce symptoms:

Eliminate all suspected food allergens, including dairy, wheat (gluten), soy, chocolate, corn, preservatives and food additives. Your health care provider may want to test for food sensitivities.
Eat more antioxidant rich foods (such as green leafy vegetables) and fruits (such as blueberries, pomegranates and cherries).
Avoid refined foods, such as white breads, pastas, and sugar.
Eat fewer red meats and more lean meats, cold-water fish, or beans for protein.
Use healthy cooking oils, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise moderately at least 30 minutes daily, 5 days a week.

You may address nutritional deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc, and selenium.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 - 3 tablespoonfuls oil, one to three times daily, to help decrease inflammation and help with immunity. Cold-water fish, such as salmon or halibut, are good sources, but are not substitutes for supplementation.
Vitamin C, 500 - 1,000 mg, one to three times daily, as an antioxidant and for immune support.
L-glutamine, 500 - 1,000 mg three times daily, for support of gastrointestinal health and immunity.
Probiotic supplement (containing Lactobacillus acidophilus), 5 - 10 billion CFUs (colony forming units) a day, when needed for maintenance of gastrointestinal and immune health. Some products may require refrigeration -- check labels carefully.
Grapefruit seed extract (Citrus paradisi), 100 mg capsule or 5 - 10 drops (in favorite beverage) three times daily when needed, for antibacterial, antifungal, and antiviral activity, and for immunity.
Resveratrol (from red wine), 50 - 200 mg daily, to help decrease inflammation and for antioxidant effects.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant and immune activity.

Herbs

Herbs are generally available as standardized, dried extracts (pills, capsules, or tablets), teas, or tinctures/liquid extracts (alcohol extraction, unless otherwise noted). Mix liquid extracts with favorite beverage. Dose for teas is 1 - 2 heaping teaspoonfuls/cup water steeped for 10 - 15 minutes (roots need longer).

Green tea (Camelia sinensis) standardized extract, 250 - 500 mg daily, for inflammation, and for antioxidant and immune effects. Use caffeine free products. You may also prepare teas from the leaf of this herb.
Milk thistle (Silybum marianum) seed standardized extract, 80 - 160 mg two to three times daily, for detoxification support.
Bromelain (Ananus comosus) standardized, 40 mg three times daily, for inflammation.
Turmeric (Curcuma longa) standardardized extract, 300 mg three times a day, for inflammation.
Cat's claw (Uncaria tomentosa) standardized extract, 20 mg three times a day, for inflammation.

Acupuncture

The American Academy of Medical Acupuncture endorses the use of acupuncture for allergies such as food allergies. Acupuncture can help restore normal immune function.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider individualized remedies for the treatment of food allergy based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type -- your physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for a particular individual.

Other Considerations

Pregnancy

Women who have a food allergy or a partner with a food allergy may be able to reduce the risk of allergy in their child by avoiding common allergenic foods during pregnancy and nursing.

Prognosis and Complications

Food allergies may cause symptoms ranging from mild abdominal discomfort to life-threatening anaphylaxis. Avoiding offending foods may be easy if the food is uncommon or easily identified. However, successful avoidance of offending foods requires strict reading of all ingredients in a package and detailed inquiries when eating away from home. Children may outgrow food allergies (particularly to milk or soy), but adults are unlikely to lose their allergies.

Supporting Research

Carey CF, Lee HH, Woeltje KF, eds. The Washington Manual of Medical Therapeutics. 29th ed. New York, NY: Lippincott-Raven; 1998:216-217, 223-225.

Chandra RK. Food allergy. Indian J Pediatr. 2002;69(3):251-255.

Friedrich MJ. A bit of culture for children: probiotics may improve health and fight disease. JAMA. 2000;284(11):1365-1366.

Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomized placebo controlled trial. Lancet. 2001;357(9262):1076-1079.

Knight AK, Bahna SL. Diagnosis of food allergy. Pediatr Ann. 2006;35(10):709-14.

Kukkonen K, Savilahti E, Haahtela T, et al. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2007;119(1):192-8.

Hill DJ, Roy N, Heine RG, et al. Effect of a low-allergen maternal diet on colic among breastfed infants: a randomized, controlled trial. Pediatrics. 2005;116(5):e709-15.

Host A, Halken S. Primary prevention of food allergy in infants who are at risk. Curr Opin Allergy Clin Immunol. 2005;5(3):255-9.

Hourihane JO. Recent advances in peanut allergy. Curr Opin allergy Clin Immunol. 2002;2(3):227-231.

Noh G, Ahn HS, Cho NY, Lee S, Oh JW. The clinical significance of food specific IgE/IgG4 in food specific atopic dermatitis. Pediatr Allergy Immunol. 2007;18(1):63-70.

Osborn D, Sinn J. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev. 2007;4:CD006475.

Patil SP, Napihadkar PV, Bapat MM. Chickpea: a major food allergen in the Indian subcontinent and its clinical and immunochemical correlation. Ann Allergy Asthma Immunol. 2001;87(2):140-145.

Ring J, Mohrenschlager M. Allergy to peanut oil - clinically relevant? J Eur Acad Dermatol Venereol. 2007 Apr;21(4):452-5.

Sampson HA. Clinical practice. Peanut allergy. N Engl J Med. 2002;346(17):1294-1299.

Sampson HA. Food allergy. JAMA. 1997; 278:1888-1894.

Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet. 2002;360:901-907.

Seppo L, Korpela R, Lonnerdal B, et al. A follow-up study of nutrient intake, nutritional status, and growth in infants with cow milk allergy fed either a soy formula or an extensively hydrolyzed whey formula. Am J Clin Nutr. 2005;82(1):140-5.

Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007;62(11):1261-1269.

Vadas P, Wai Y, Burks W, Perelman B. Detection of peanut allergens in breast milk of lactating women. JAMA. 2001;285(13):1746-1748.

Vlieg-Boerstra BJ, van der Heide S, Bijleveld CM, et al. Placebo reactions in double-blind, placebo-controlled food challenges in children. Allergy. 2007;62(:905-12.

Review Date:
11/30/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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Infantile colic

FitSugar — Wed, 08 Oct 2008 17:35:25 -0700

Overview

Signs and Symptoms
What Causes It?
What to Expect at Your Provider's Office
Treatment Options
Following Up
Special Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Colicky babies cry constantly and hard at about the same time each day at least 3 days a week. About one in five babies develops colic. It is more common in boys and in firstborn children. It usually begins at about 2 weeks of age and goes away by the fourth month.

Signs and Symptoms

Your baby cries for more than 3 hours on at least three occasions a week, but is otherwise healthy.
Your baby kicks a lot, pulls their legs up close, and makes tight fists.
Your baby's tummy seems hard, and the baby burps and passes gas often.
The crying sounds like your baby is in great pain.
Your baby spits up frequently after feeding.

What Causes It?

Abdominal discomfort appears to be present, but one knows what actually causes colic. Possible causes include one or more of the following:

The baby's nervous or digestive system may be immature.
The baby needs comforting, or is over- or under-stimulated.
The baby swallows air, especially when feeding
The baby may be reacting to something in the mother's diet (if the baby is breastfed).
The baby has allergies to some foods, such as milk (if the baby is on formula).

What to Expect at Your Provider's Office

Your health care provider will ask if the baby is eating well and gaining weight or has diarrhea, fever, or unusual stools. If you are breastfeeding, your health care provider may ask about foods you have eaten. If your health care provider decides your baby has colic, you can work together to find ways to relieve your baby's discomfort.

Your health care provider will also encourage you to take care of yourself, like taking a break or getting help if you are afraid you will harm your baby. Remember that colic usually disappears between 4 - 6 months of age. If the treatments you choose do not work, your baby's health care provider may check for other problems, such as a digestive problem or allergy.

Treatment Options

If breastfeeding, nurse on demand, usually every 2 - 3 hours. Avoid caffeine, dairy products, citrus fruits, soy products, and spicy foods. Elevate the infant's head during and after feedings.
If bottle-feeding, ask your health care provider to recommend a formula that is not based on cow's milk and that is not iron-fortified. Keep the baby in a sitting position when feeding, and massage their back to get rid of gas bubbles. Burp after every ounce of formula.
Do not offer your baby solid foods before age 6 months.
Try the "colic carry" -- Place the baby, chest down, on your extended forearm, with their head supported by your hand and legs on either side of your elbow. Use your other hand to provide additional support and walk around with the baby.
Hold your baby close, offer a pacifier, try rocking or rubbing the back, give your baby a warm bath, take a car ride with the baby, play soft music, or use an infant swing to ease the crying.

Drug Therapies

No drugs are recommended, although simethicone, an over-the-counter gas remedy, may be helpful.

Complementary and Alternative Therapies

Eliminating gas-producing foods and using supportive herbal or homeopathic therapies may help reduce or eliminate infantile colic. Colic may be caused by a hidden food allergy. As a result, you may need to switch formula or food. A qualified natural health care provider can help you find nutritious hypo-allergenic foods for your child. If you are breastfeeding, eliminating gas-producing and potentially allergic foods from your diet may help. In addition, playing soft music, rocking the infant, or using "white noise" (for example, a dryer or even a vacuum cleaner) may be helpful in soothing the infant. Reducing stimuli and placing the infant in a dim, quiet room may help calm the baby.

Nutrition and Supplements

Acidophilus (especially Bifidusspp. ) can be given to both a breastfeeding mother and infant who takes a bottle, whether of breast milk or formula. Use 1 capsule (containing 5 - 10 billion CFUs per capsule) with meals three times per day for adults. Use one capsule per day for infants (break capsule open and add to bottle in divided doses throughout the day). Use acidophilus formulas specifically formulated for infants, such as Baby Jarrow-Dophilus. Some acidophilus products may need refrigeration. It is important to read the label carefully.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems, although many herbs that may be safe for adults may NOT be suitable for infants. As with any therapy, you should work with the baby's health care provider to get the problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas) or glycerites (glycerine extracts). Because of the alcohol content, do not give tinctures (alcohol extracts) to infants unless directed by your health care provider. Unless otherwise indicated, make teas with 1 tsp. hof erb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink two to four cups per day.

Inform your child's pediatrician about any herbs you may be using for your child and work with a qualified health care provider to develop the safest and most effective home remedy kit for your family.

You may give a tea made from fennel seed (Foeniculum vulgare) directly to the infant (1 tsp. before and after feedings) after it cools, or a breastfeeding mohter can drink it (1 cup three to six times per day). Fennel acts as a gastrointestinal relaxant and helps expel gas.

Teas and liquids made with the following herbs may also help:

Chamomile (Matricaria recutita ), vervain (Verbena officinalis ), fennel (Foeniculum vulgare ), and lemon balm (Melissa officinalis). Give about 1/2 cup of tea up to three times per day.
Caraway (Carum carvi) helps reduce intestinal cramping. Combine 1 teaspoon of caraway seed with 8 ounces boiled water and steep for 10 minutes. Add 3 ounces of vegetable glycerin. Strain and give a 1/2 teaspoon 15 minutes before feeding.
Other herbs that may help reduce calm the baby or reduce gas include linden (Tilia cordata), catnip (Nepeta cataria), peppermint (Mentha piperita), and dill (Anethum graveolens ). They can be combined with the teas above.
Slippery elm bark (Ulmus fulva) helps soothe the digestive system and can be used as a tea. You can also combine the powdered bark with water and make a meal of slippery elm “gruel," similar in consistency to instant oatmeal. Check with your child's pediatrician first before using slippery elm gruel in your child’s diet.

Homeopathy

Few studies have examined the effectiveness of specific homeopathic remedies. However, a professional homeopath may recommend one or more of the following treatments for infantile colic based on their knowledge and clinical experience.

Viburcol, a proprietary homeopathic medicine often used in Europe, can be very effective for acute colic. It contains Chamomilla, Belladonna, Dulcamara, Plantago major, Pulsatilla, and Calcium carbonicum Hahnemanni.

Aethusa -- for infants who cannot digest milk, who vomit, and have diarrhea.
Belladonna -- for colic with spasms that come and go quickly. The abdomen may feel warm to the touch and symptoms may coincide with constipation. Bending forward may relieve pain.
Bryonia -- for pain worsened by movement and pressure. This remedy is most appropriate for irritable infants who lie still with knees drawn up.
Carbo vegetabilis-- for colic with a distended abdomen and burping or belching. The face may be pale, and hands and feet feel cold.
Chamomilla -- for excessively irritable and screaming infants who are relieved by constant holding and rocking. Infants for whom this remedy is appropriate are often teething and have green, foul-smelling diarrhea.
Colocynthis -- for restless, irritable infants whose symptoms of colic are relieved by firm pressure. In these infants, diarrhea and pain may occur after eating fruit. Infant tends to bring knees up to their abdomen.
Lycopodium -- for infants who can not stand pressure on the abdomen (even diapers must be worn loosely). Symptoms tend to worsen between 4 and 8 p.m., and then again after midnight.
Magnesia phos -- for infants whose symptoms of colic are relieved with gentle pressure or warmth applied to the abdomen, or while they are bent over. Belching does not relieve pain.
Natrum phos --for colic with no other distinguishing symptoms.
Nux vomica --for colic that occurs when a breastfeeding mother eats rich food, drinks alcohol, or coffee. The infant may arch its back and appear angry.
Pulsatilla --for infants with bloated abdomens after eating, and constipation alternating with diarrhea. May be aggravated by warm rooms, heat, or if the diet of the breastfeeding mother includes fruits, fats, pastries, or ice cream. Relieved by rocking.

Chiropractic

Chiropractors frequently treat infantile colic with a form of gentle spinal manipulation specially modified for infants. The duration of treatment is generally brief, consisting of three to four visits over a period of 2 weeks. Studies examining the effectiveness of chiropractic for infantile colic have produced mixed results, however.

Physical Medicine

Warm baths may help relax and soothe colicky infants. Add three to four drops of essential oil of lavender or lemon balm to enhance the benefit.

Gently pinching or squeezing the acupressure point between the baby's thumb and finger (on the webbing) may help to calm a fussy child.

Massage

Clockwise abdominal massage may help relieve spasm and expel gas. Use three to five drops of tincture of catnip in 1 - 2 tsp. of almond or olive oil to enhance effectiveness. Apply warmth.

Following Up

Use whatever works, and remember that your baby will outgrow the colic in a few weeks or months. Keep in mind, however, that colicky babies often grow up to have other allergy-related health problems, such as ear infections, asthma, and digestive problems.

Special Considerations

Never shake your baby. This can cause serious or fatal brain damage. If you are feeling overwhelmed, try the following steps:

Have someone else watch your baby while you get away for a while.
Join a support group.
Call your baby's health care provider.

Supporting Research

Alexandrovich I, Rakovitskaya O, Kolmo E, et al. The effect of fennel (Foeniculum vulgare) seed oil emulsion in infantile colic: a randomized, placebo-controlled study. Altern Ther Health Med. 2003;9:58-61.

Boericke W. Materia Medica. 9th ed. Santa Rosa, Calif: Boericke and Tafel; 1927:151.

Crotteau CA, Wright ST, Eglash A. Clinical inquiries. What is the best treatment for infants with colic? J Fam Pract. 2006;55(7):634-6.

Gupta SK. Update on infantile colic and management options. Curr Opin Investig Drugs. 2007;8(11):921-6.

Herman M, Le A. The crying infant. Emerg Med Clin North Am. 2007;25(4):1137-59, vii.

Howard CR, Lanphear N, Lanphear BP, Eberly S, Lawrence RA. Parental responses to infant crying and colic: the effect on breastfeeding duration. Breastfeed Med. 2006;1(3):146-55.

Pina DI, Llach XB, Arino-Armengol B, Iglesias VV. Prevalence and dietetic management of mild gastrointestinal disorders in milk-fed infants. World J Gastroenterol. 2008;14(2):248-54.

Rosen LD, Bukutu C, Le C, Shamseer L, Vohra S. Complementary, holistic, and integrative medicine: colic. Pediatr Rev. 2007;28(10):381-5.

Savino F, Cresi F, Castagno E, et al. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officialis (ColiMil) in the treatment of breast-fed colicky infants. Phytother Res. 2005;19:335-40.

Savino F. Focus on infantile colic. Acta Paediatr. 2007;96(9):1259-64.

Wade S. Infantile colic. Clin Evid. 2006;(15):439-47.

Zwart P, Vellema-Goud MG, Brand PL. Characteristics of infants admitted to hospital for persistent colic, and comparison with healthy infants. Acta Paediatr. 2007;96(3):401-5.

Review Date:
2/12/2008
Reviewed By:
Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network. Also reviewed by Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources,

A.D.A.M. Copyright

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Aprotinin/calcium chloride/fibrinogen/thrombin (On the skin)

admin — Thu, 04 Sep 2008 20:13:44 -0700

Overview

Introduction
Brand Name(s)
When This Medicine Should Not Be Used
How to Use This Medicine
Drugs and Foods to Avoid
Warnings While Using This Medicine
Possible Side Effects While Using This Medicine

HEALTH GUIDE REFERENCE FROM A.D.A.M

Introduction

Controls bleeding during surgery.

Brand Name(s)

There may be other brand names for this medicine.

When This Medicine Should Not Be Used

You should not receive this medicine if you have had an allergic reaction to aprotinin, calcium chloride, fibrinogen, thrombin, or bovine proteins (from animals such as oxen or cows).

How to Use This Medicine

Kit

A nurse or other trained health professional will give you this medicine.

Drugs and Foods to Avoid

Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

Warnings While Using This Medicine

Make sure your doctor knows if you are pregnant or breastfeeding.
This medicine is made from donated human blood. Some human blood products have transmitted certain viruses to people who have received them. The risk of getting a virus from human blood products has been greatly reduced because all donated blood must be tested before any products are made. Talk with your doctor if you have any concerns about this risk.

Possible Side Effects While Using This Medicine

Call your doctor right away if you notice any of these side effects:

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.
Fast or slow heartbeat.
Fever or chills.
Joint pain.
Lightheadedness or fainting.
Nausea.
Skin rash.
Warmth or redness in your face, neck, arms, or upper chest.

Review Date: 8/4/2008

A.D.A.M. Copyright

adam.com

Source Doc: 45_5600

Pegademase bovine (Injection)

admin — Thu, 04 Sep 2008 20:10:23 -0700

Overview

Introduction
Brand Name(s)
When This Medicine Should Not Be Used
How to Use This Medicine
How to Store and Dispose of This Medicine
Drugs and Foods to Avoid
Warnings While Using This Medicine
Possible Side Effects While Using This Medicine

HEALTH GUIDE REFERENCE FROM A.D.A.M

Introduction

Pegademase Bovine (peg-A-de-mase BOE-vine)

Replaces enzymes in adenosine deaminase (ADA) deficiency.

Brand Name(s)

Adagen

There may be other brand names for this medicine.

When This Medicine Should Not Be Used

You should not use this medicine if you have had an allergic reaction to pegademase bovine or to any product made from a cow. You should not use this medicine if you have severe thrombocytopenia.

How to Use This Medicine

Injectable

Your doctor will tell you how much of this medicine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.
Your doctor will prescribe your exact dose and tell you how often it should be given. This medicine is given as a shot into one of your muscles.
A nurse or other trained health professional will give you this medicine.
You may be taught how to give your medicine at home. Make sure you understand all instructions before giving yourself an injection. Do not use more medicine or use it more often than your doctor tells you to.
Use a new needle and syringe each time you inject your medicine.

If a dose is missed:

Call your doctor or pharmacist for instructions.

How to Store and Dispose of This Medicine

If you store this medicine at home, keep it in the refrigerator. Do not freeze.
Keep all medicine away from children and never share your medicine with anyone.
Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any leftover medicine, containers, and other supplies. You will also need to throw away old medicine after the expiration date has passed.

Drugs and Foods to Avoid

Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

Make sure your doctor knows if you are using medicine to treat viral infection such as vidarabine.
Make sure your doctor knows about all other medicines you are using.

Warnings While Using This Medicine

Make sure your doctor knows if you are pregnant or breast feeding.
Make sure your doctor knows if you have bleeding problems, or if you ever had a bone marrow transplant.
There are many other drugs that can interact with pegademase bovine. Make sure your doctor knows about all other medicines you are using.
Your doctor will need to check your blood at regular visits while you are using this medicine. Be sure to keep all appointments.

Possible Side Effects While Using This Medicine

Call your doctor right away if you notice any of these side effects:

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.

If you notice these less serious side effects, talk with your doctor:

Headache.
Pain, itching, burning, swelling, or a lump under your skin where the shot is given.

Review Date: 8/4/2008

A.D.A.M. Copyright

adam.com

Source Doc: 45_5354

Thrombin (On the skin)

admin — Thu, 04 Sep 2008 20:08:00 -0700

Overview

Introduction
Brand Name(s)
When This Medicine Should Not Be Used
How to Use This Medicine
Drugs and Foods to Avoid
Warnings While Using This Medicine
Possible Side Effects While Using This Medicine

HEALTH GUIDE REFERENCE FROM A.D.A.M

Introduction

Thrombin (THROM-bin)

Controls minor bleeding or bleeding during surgery.

Brand Name(s)

Recothrom, Thrombin-JMI

There may be other brand names for this medicine.

When This Medicine Should Not Be Used

You should not receive this medicine if you have had an allergic reaction to thrombin or other human blood products. This medicine should not be given as an injection or used to treat severe bleeding.

How to Use This Medicine

Kit, Liquid, Powder for Solution

A nurse or other trained health professional will give you this medicine.
This medicine is applied only to your skin or incision during surgery. It may be used with a sponge.

Drugs and Foods to Avoid

Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

Warnings While Using This Medicine

Make sure your doctor knows if you are pregnant or breastfeeding, or if you have ever had an allergic reaction to any bovine (animals such as ox or cow) products.
This medicine is made from donated human blood. Some human blood products have transmitted certain viruses to people who have received them. The risk of getting a virus from medicines made of human blood has been greatly reduced in recent years. This is the result of required testing of human donors for certain viruses, and testing during manufacture of these medicines. Although the risk is low, talk with your doctor if you have concerns.
Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain medical tests.

Possible Side Effects While Using This Medicine

Call your doctor right away if you notice any of these side effects:

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.
Chest pain, shortness of breath, or coughing up blood.
Numbness or weakness in your arm or leg, or on one side of your body.
Pain in your lower leg (calf).
Sudden or severe headache, problems with vision, speech, or walking.

If you notice these less serious side effects, talk with your doctor:

Itching where the medicine is applied.

Review Date: 8/4/2008

A.D.A.M. Copyright

adam.com

Source Doc: 45_5176