INFO GURU

Alzheimer's disease (AD) is a progressive disease of the brain that is characterized by impairment of memory and a disturbance in at least one other thinking function (for example, language or perception of reality). Many scientists believe that AD results from an increase in the production or accumulation of a specific protein (beta-amyloid protein) that leads to nerve cell death. Loss of nerve cells in strategic brain areas, in turn, causes deficits in the neurotransmitters, which are the brain's chemical messengers.

What is Alzheimer's disease?

Alzheimer's disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of memory and eventually by disturbances in reasoning, planning, language, and perception. Many scientists believe that Alzheimer's disease results from an increase in the production or accumulation of a specific protein (beta-amyloid protein) in the brain that leads to nerve cell death.

The likelihood of having Alzheimer's disease increases substantially after the age of 70 and may affect around 50% of persons over the age of 85. Nonetheless, Alzheimer's disease is not a normal part of aging and is not something that inevitably happens in later life. For example, many people live to over 100 years of age and never develop Alzheimer's disease.

Who develops Alzheimer's disease?

The main risk factor for Alzheimer's disease is increased age. As a population ages, the frequency of Alzheimer's disease continues to increase. Ten percent of people over 65 years of age and 50% of those over 85 years of age have Alzheimer's disease. Unless new treatments are developed to decrease the likelihood of developing Alzheimer's disease, the number of individuals with Alzheimer's disease in the United States is expected to be 14 million by the year 2050.

There are also genetic risk factors for Alzheimer's disease. Most patients develop Alzheimer's disease after age 70. However, 2%-5% of patients develop the disease in the fourth or fifth decade of life (40s or 50s). At least half of these early onset patients have inherited gene mutations associated with their Alzheimer's disease. Moreover, the children of a patient with early onset Alzheimer's disease who has one of these gene mutations has a 50% risk of developing Alzheimer's disease.

There is also a genetic risk for late onset cases. A relatively common form of a gene located on chromosome 19 is associated with late onset Alzheimer's disease. In the majority of Alzheimer's disease cases, however, no specific genetic risks have yet been identified.

Other risk factors for Alzheimer's disease includehigh blood pressure (hypertension), coronary artery disease, diabetes, and possibly elevated blood cholesterol. Individuals who have completed less than eight years of education also have an increased risk for Alzheimer's disease. These factors increase the risk of Alzheimer's disease, but by no means do they mean that Alzheimer's disease is inevitable in persons with these factors.
All patients with Down syndrome will develop the brain changes of Alzheimer's disease by 40 years of age. This fact was also a clue to the "amyloid hypothesis of Alzheimer's disease"

Symptoms

The onset of Alzheimer's disease is usually gradual, and it is slowly progressive. Memory problems that family members initially dismiss as "a normal part of aging" are in retrospect noted by the family to be the first stages of Alzheimer's disease. When memory and other problems with thinking start to consistently affect the usual level of functioning; families begin to suspect that something more than "normal aging" is going on.

Problems of memory, particularly for recent events (short-term memory) are common early in the course of Alzheimer's disease. For example, the individual may, on repeated occasions, forget to turn off an iron or fail to recall which of the morning's medicines were taken. Mild personality changes, such as less spontaneity, apathy, and a tendency to withdraw from social interactions, may occur early in the illness.

As the disease progresses, problems in abstract thinking and in other intellectual functions develop. The person may begin to have trouble with figures when working on bills, with understanding what is being read, or with organizing the day's work. Further disturbances in behavior and appearance may also be seen at this point, such as agitation, irritability, quarrelsomeness, and a diminishing ability to dress appropriately.

Later in the course of the disorder, affected individuals may become confused or disoriented about what month or year it is, be unable to describe accurately where they live, or be unable to name a place being visited. Eventually, patients may wander, be unable to engage in conversation, erratic in mood, uncooperative, and lose bladder and bowel control. In late stages of the disease, persons may become totally incapable of caring for themselves. Death can then follow, perhaps from pnuemonia or some other problem that occurs in severely deteriorated states of health. Those who develop the disorder later in life more often die from other illnesses (such as heart disease) rather than as a consequence of Alzheimer's disease.

Causes of Alzheimer's disease

The cause(s) of Alzheimer's disease is (are) not known. The "amyloid cascade hypothesis" is the most widely discussed and researched hypothesis about the cause of Alzheimer's disease. The strongest data supporting the amyloid cascade hypothesis comes from the study of early-onset inherited (genetic) Alzheimer's disease. Mutations associated with Alzheimer's disease have been found in about half of the patients with early-onset disease. In all of these patients, the mutation leads to excess production in the brain of a specific form of a small protein fragment called ABeta (Aβ). Many scientists believe that in the majority of sporadic (for example, non-inherited) cases of Alzheimer's disease (these make up the vast majority of all cases of Alzheimer's disease) there is too little removal of this Aβ protein rather than too much production. In any case, much of the research in finding ways to prevent or slow down Alzheimer's disease has focused on ways to decrease the amount of Aβ in the brain.

Risk factors for Alzheimer's disease

The biggest risk factor for Alzheimer's disease is increased age. The likelihood of developing Alzheimer's disease doubles every 5.5 years from 65 to 85 years of age. Whereas only 1%-2% of individuals 70 years of age have Alzheimer's disease, in some studies around 40% of individuals 85 years of age have Alzheimer's disease. Nonetheless, at least half of people who live past the 95 years of age do not have Alzheimer's disease.

Common forms of certain genes increase the risk of developing Alzheimer's disease, but do not invariably cause Alzheimer's disease. The best-studied "risk" gene is the one that encodes apolipoprotein E (apoE). The apoE gene has three different forms (alleles) -- apoE2, apoE3, and apoE4. The apoE4 form of the gene has been associated with increased risk of Alzheimer's disease in most (but not all) populations studied. The frequency of the apoE4 version of the gene in the general population varies, but is always less than 30% and frequently 8%-15%. Persons with one copy of the E4 gene usually have about a two to three fold increased risk of developing Alzheimer's disease. Persons with two copies of the E4 gene (usually around 1% of the population) have about a nine-fold increase in risk. Nonetheless, even persons with two copies of the E4 gene don't always get Alzheimer's disease. At least one copy of the E4 gene is found in 40% of patients with sporadic or late-onset Alzheimer's disease.

This means that in majority of patients with Alzheimer's disease, no genetic risk factor has yet been found. Most experts do not recommend that adult children of patients with Alzheimer's disease should have genetic testing for the apoE4 gene since there is no treatment for Alzheimer's disease. When medical treatments that prevent or decrease the risk of developing Alzheimer's disease become available, genetic testing may be recommended for adult children of patients with Alzheimer's disease so that they may be treated.

Many, but not all, studies have found that women have a higher risk for Alzheimer's disease than men. It is certainly true that women live longer than men, but age alone does not seem to explain the increased frequency in women. The apparent increased frequency of Alzheimer's disease in women has led to considerable research about the role of estrogen in Alzheimer's disease. Recent studies suggest that estrogen should not be prescribed to post-menopausal women for the purpose of decreasing the risk of Alzheimer's disease. Nonetheless, the role of estrogen in Alzheimer's disease remains an area of research focus.

Some studies have found that Alzheimer's disease occurs more often among people who suffered significant traumatic head injuries earlier in life, particularly among those with the apoE 4 gene.

In addition, many, but not all studies, have demonstrated that persons with limited formal education – usually less than eight years – are at increased risk for Alzheimer's disease. It is not known whether this reflects a decreased "cognitive reserve" or other factors associated with a lower educational level.

Treatment and management options are available for Alzheimer's disease

The management of Alzheimer's disease consists of medication based and non-medication based treatments. Two different classes of pharmaceuticals are approved by the FDA for treating Alzheimer's disease: cholinesterase inhibitors and partial glutamate antagonists. Neither class of drugs has been proven to slow the rate of progression of Alzheimer's disease. Nonetheless, many clinical trials suggest that these medications are superior to placebos (sugar pills) in relieving some symptoms.

Cholinesterase inhibitors

In patients with Alzheimer's disease there is a relative lack of a brain chemical neurotransmitter called acetylcholine. (Neurotransmitters are chemical messengers produced by nerves that the nerves use to communicate with each other in order to carry out their functions.) Substantial research has demonstrated that acetylcholine is important in the ability to form new memories. The cholinesterase inhibitors (ChEIs) block the breakdown of acetylcholine. As a result, more acetylcholine is available in the brain, and it may become easier to form new memories.

Four ChEIs have been approved by the FDA, but onlydonepezil hydrochloride (Aricept), rivastigmine (Exelon), and galantamine (Razadyne - previously called Reminyl) are used by most physicians because the fourth drug, tacrine (Cognex) has more undesirable side effects than the other three. Most experts in Alzheimer's disease do not believe there is an important difference in the effectiveness of these three drugs. Several studies suggest that the progression of symptoms of patients on these drugs seems to plateau for six to 12 months, but inevitably progression then begins again.
Of the three widely used AchEs, rivastigmine and galantamine are only approved by the FDA for mild to moderate Alzheimer's disease, whereas donepezil is approved for mild, moderate, and severe Alzheimer's disease. It is not known whether rivastigmine and galantamine are also effective in severe Alzheimer's disease, although there does not appear to be any good reason why they shouldn't.
The principal side effects of ChEIs involve the gastrointestinal system and include nausea, vomiting, cramping, and diarrhea. Usually these side effects can be controlled with change in size or timing of the dose or administering the medications with a small amount of food. Between 75% and 90% of patients will tolerate therapeutic doses of ChEIs.

Partial glutamate antagonists

Glutamate is the major excitatory neurotransmitter in the brain. One theory suggests that too much glutamate may be bad for the brain and cause deterioration of nerve cells. Memantane (Namenda) works by partially decreasing the effect of glutamate to activate nerve cells. It has not been proven that memantine slows down the rate of progression of Alzheimer's disease. Studies have demonstrated that some patients on memantine can care for themselves better than patients on sugar pills (placebos). Memantine is approved for treatment of moderate and severe dementia, and studies did not show it was helpful in mild dementia. It is also possible to treat patients with both AchEs and memantine without loss of effectiveness of either medication or an increase in side effects.

Non-medication based treatments

Non-medication based treatments include maximizing patients' opportunities for social interaction and participating in activities such as walking, singing, dancing that they can still enjoy. Cognitive rehabilitation, (whereby a patient practices on a computer program for training memory), may or may not be of benefit. Further studies of this method are needed.

Treatment of psychiatric symptoms

Symptoms of Alzheimer's disease include agitation, depression, hallucinations, anxiety, and sleep disorders. Standard psychiatric drugs are widely used to treat these symptoms although none of these drugs have been specifically approved by the FDA for treating these symptoms in patients with Alzheimer's disease. If these behaviors are infrequent or mild, they often do not require treatment with medication. Non-pharmacologic measures can be very useful.

Nevertheless, frequently these symptoms are so severe that it becomes impossible for caregivers to take care of the patient, and treatment with medication to control these symptoms becomes necessary. Agitation is common, particularly in middle and later stages of Alzheimer's disease. Many different classes of agents have been tried to treat agitation including:

• antipsychotics,
  
  
• mood-stabilizing anticonvulsants,
  
  
• trzadone (Desyrel),
  
  
• anxiolytics,
  
  

Studies are conflicting about the usefulness of these different drug classes. It was thought that newer, atypical antipsychotic agents such as clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa, Zydis), quetiapine (Seroquel), and ziprasidone (Geodon) might have advantages over the older antipsychotic agents because of their fewer and less severe side effects and the patients' ability to tolerate them. However, more recent studies have not demonstrated superiority of the newer antipsychotics. Some research shows that these newer antipsychotics may be associated with increased risk of stroke or sudden death than the older antipsychotics, but many physicians believe this question is still not resolved.
Apathy and difficulty concentrating occur in most Alzheimer's disease patients and should not be treated with antidepressant medications. However, many Alzheimer's disease patients have other symptoms of depression including sustained feelings of unhappiness and/or inability to enjoy their usual activities. Such patients may benefit from a trial of antidepressant medication. Most physicians will try selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft), citalopram (Celexa), or fluoxetine (Prozac), as first-line agents for treating depression in Alzheimer's disease.
Anxiety is another symptom in Alzheimer's disease that occasionally requires treatment. Benzodiazepines such as diazepam (Valium) or lorazepam (Ativan) may be associated with increased confusion and memory impairment. Non-benzodiazepine anxiolytics, such as buspirone (Buspar) or SSRIs, are probably preferable.
Difficulty sleeping (insomnia) occurs in many patients with Alzheimer's disease at some point in the course of their disease. Many Alzheimer's disease specialists prefer the use of sedating atypical antidepressants such as trazodone (Desyrel). However, other specialists may recommend other classes of medications. Sleep improvement measures, such as sunlight, adequate treatment of pain, and limiting nighttime fluids to prevent the need for urination, should also be implemented.

• Diabetes is a chronic condition associated with abnormally high levels of sugar (glucose) in the blood.
• Insulin produced by the pancreas lowers blood glucose.
• Absence or insufficient production of insulin causes diabetes.
• The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent).
• Symptoms of diabetes include increased urine output, thirst and hunger as well as fatigue.
• Diabetes is diagnosed by blood sugar (glucose) testing.
• The major complications of diabetes are both acute and chronic.
  • Acutely: dangerously elevated blood sugar, abnormally low blood sugar due to diabetes medications may occur.
  • Chronically: disease of the blood vessels (both small and large) which can damage the eye, kidneys, nerves, and heart may occur
• Diabetes treatment depends on the type and severity of the diabetes. Type 1 diabetes is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes is first treated with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, insulin medications are considered.

What is diabetes?

Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar (glucose) levels, which result from defects in insulin secretion, or action, or both. Diabetes mellitus, commonly referred to as diabetes (as it will be in this article) was first identified as a disease associated with “sweet urine," and excessive muscle loss in the ancient world. Elevated levels of blood glucose (hyperglycemia) lead to spillage of glucose into the urine, hence the term sweet urine. Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to normalize the glucose level. In patients with diabetes, the absence or insufficient production of insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.

What is the impact of diabetes?

Over time, diabetes can lead to blindness, kidney failure, and nerve damage. These types of damage are the result of damage to small vessels, referred to as microvascular disease. Diabetes is also an important factor in accelerating the hardening and narrowing of the arteries (atherosclerosis), leading to strokes, coronary heart disease, and other large blood vessel diseases. This is referred to as macrovascular disease. Diabetes affects approximately 17 million people (about 8% of the population) in the United States. In addition, an estimated additional 12 million people in the United States have diabetes and don't even know it. From an economic perspective, the total annual cost of diabetes in 1997 was estimated to be 98 billion dollars in the United States. The per capita cost resulting from diabetes in 1997 amounted to $10,071.00; while healthcare costs for people without diabetes incurred a per capita cost of $2,699.00. During this same year, 13.9 million days of hospital stay were attributed to diabetes, while 30.3 million physician office visits were diabetes related. Remember, these numbers reflect only the population in the United States. Globally, the statistics are staggering.
Diabetes is the third leading cause of death in the United States after heart disease and cancer.

What causes diabetes?

Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as "insulin resistance." This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. For more, please read the Insulin Resistance article. Essentially, if someone is resistant to insulin, the body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycemia develops.
Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilized. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, the cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine.
Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).

What are the different types of diabetes?

There are two major types of diabetes, called type 1 and type 2. Type 1 diabetes was also called insulin dependent diabetes mellitus (IDDM), or juvenile onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in the majority of patients with type 1 diabetes. Antibodies are proteins in the blood that are part of the body's immune system. The patient with type 1 diabetes must rely on insulin medication for survival.
In autoimmune diseases, such as type 1 diabetes, the immune system mistakenly manufactures antibodies and inflammatory cells that are directed against and cause damage to patients' own body tissues. In persons with type 1 diabetes, the beta cells of the pancreas, which are responsible for insulin production, are attacked by the misdirected immune system. It is believed that the tendency to develop abnormal antibodies in type 1 diabetes is, in part, genetically inherited, though the details are not fully understood. Exposure to certain viral infections (mumps and Coxsackie viruses) or other environmental toxins may serve to trigger abnormal antibody responses that cause damage to the pancreas cells where insulin is made. These antibodies can be measured in the majority of patients, and may help determine which individuals are at risk for developing type 1 diabetes.
At present, the American Diabetes Association does not recommend general screening of the population for type 1 diabetes, though screening of high risk individuals, such as those with a first degree relative (sibling or parent) with type 1 diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean individuals, usually before 30 years of age, however, older patients do present with this form of diabetes on occasion. This subgroup is referred to as latent autoimmune diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Of all the patients with diabetes, only approximately 10% of the patients have type 1 diabetes and the remaining 90% have type 2 diabetes.
Type 2 diabetes was also referred to as non-insulin dependent diabetes mellitus (NIDDM), or adult onset diabetes mellitus (AODM). In type 2 diabetes, patients can still produce insulin, but do so relatively inadequately for their body's needs, particularly in the face of insulin resistance as discussed above. In many cases this actually means the pancreas produces larger than normal quantities of insulin. A major feature of type 2 diabetes is a lack of sensitivity to insulin by the cells of the body (particularly fat and muscle cells). In addition to the problems with an increase in insulin resistance, the release of insulin by the pancreas may also be defective and suboptimal. In fact, there is a known steady decline in beta cell production of insulin in type 2 diabetes that contributes to worsening glucose control. (This is a major factor for many patients with type 2 diabetes who ultimately require insulin therapy.) Finally, the liver in these patients continues to produce glucose through a process called gluconeogenesis despite elevated glucose levels. The control of gluconeogenesis becomes compromised.
While it is said that type 2 diabetes occurs mostly in individuals over 30 years old and the incidence increases with age, we are seeing an alarming number patients with type 2 diabetes who are barely in their teen years. In fact, for the first time in the history of humans, type 2 diabetes is now more common than type 1 diabetes in childhood. Most of these cases are a direct result of poor eating habits, higher body weight, and lack of exercise.
While there is a strong genetic component to developing this form of diabetes, there are other risk factors - the most significant of which is obesity. There is a direct relationship between the degree of obesity and the risk of developing type 2 diabetes, and this holds true in children as well as adults. It is estimated that the chance to develop diabetes doubles for every 20% increase over desirable body weight.
Regarding age, data shows that for each decade after 40 years of age regardless of weight there is an increase in incidence of diabetes. The prevalence of diabetes in persons 65 to 74 years of age is nearly 20%. Type 2 diabetes is also more common in certain ethnic groups. Compared with a 6% prevalence in Caucasians, the prevalence in African Americans and Asian Americans is estimated to be 10%, in Hispanics 15%, and in certain Native American communities 20% to 50%. Finally, diabetes occurs much more frequently in women with a prior history of diabetes that develops during pregnancy (gestational diabetes - see below).
Diabetes can occur temporarily during pregnancy. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 25-50% of women with gestational diabetes will eventually develop Type 2 diabetes later in life, especially in those who require insulin during pregnancy and those who remain overweight after their delivery. Patients with gestational diabetes are usually asked to undergo an oral glucose tolerance test about 6 weeks after giving birth to determine if their diabetes has persisted beyond the pregnancy, or if any evidence (such as impaired glucose tolerance) is present that may be a clue to the patient's future risk for developing diabetes.
"Secondary" diabetes refers to elevated blood sugar levels from another medical condition. Secondary diabetes may develop when the pancreatic tissue responsible for the production of insulin is destroyed by disease, such as chronic pancreatitis (inflammation of the pancreas by toxins like excessive alcohol), trauma, or surgical removal of the pancreas. Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production (acromegaly) and Cushing's syndrome. In acromegaly, a pituitary gland tumor at the base of the brain causes excessive production of growth hormone, leading to hyperglycemia. In Cushing's syndrome, the adrenal glands produce an excess of cortisol, which promotes blood sugar elevation.
In addition, certain medications may worsen diabetes control, or "unmask" latent diabetes. This is seen most commonly when steroid medications (such as prednisone) are taken and also with medications used in the treatment of HIV infection (AIDS).

What are diabetes symptoms?

The early symptoms of untreated diabetes are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration. Dehydration causes increased thirst and water consumption. The inability of insulin to perform normally has effects on protein, fat and carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that encourages storage of fat and protein. A relative or absolute insulin deficiency eventually leads to weight loss despite an increase in appetite. Some untreated diabetes patients also complain of fatigue, nausea and vomiting. Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas. Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated glucose levels can lead to lethargy and coma.

How is diabetes diagnosed?

The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a doctor's office using a glucose meter.
Normal fasting plasma glucose levels are less than 100 milligrams per deciliter (mg/dl). Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes. A random blood glucose test can also be used to diagnose diabetes A blood glucose level of 200 mg/dl or higher indicates diabetes.
When fasting blood glucose stays above 100mg/dl, but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere.
The oral glucose tolerance test
Though not routinely used anymore, the oral glucose tolerance test (OGTT) is a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes. With an oral glucose tolerance test, the person fasts overnight (at least eight but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose (100 grams for pregnant women). There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the blood glucose.
For the test to give reliable results, the person must be in good health (not have any other illnesses, not even a cold). Also, the person should be normally active (not lying down, for example, as an inpatient in a hospital) and should not be taking medicines that could affect the blood glucose. For three days before the test, the person should have eaten a diet high in carbohydrates (150- 200 grams per day). The morning of the test, the person should not smoke or drink coffee.
The classic oral glucose tolerance test measures blood glucose levels five times over a period of three hours. Some physicians simply get a baseline blood sample followed by a sample two hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.
People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT). People with impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1-5% of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes. Recent studies have shown that impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians are now understanding that impaired glucose tolerance is nor simply a precursor of diabetes, but is its own clinical disease entity that requires treatment and monitoring.

Evaluating the results of the oral glucose tolerance test

Glucose tolerance tests may lead to one of the following diagnoses:

• Normal response: A person is said to have a normal response when the 2-hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl.
• Impaired glucose tolerance: A person is said to have impaired glucose tolerance when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.
• Diabetes: A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high.
• Gestational diabetes: A woman has gestational diabetes when she has any two of the following: a 100g OGTT, a fasting plasma glucose of more than 95 mg/dl, a 1-hour glucose level of more than 180 mg/dl, a 2-hour glucose level of more than 155 mg/dl, or a 3-hour glucose level of more than 140 mg/dl.

Why is blood sugar checked at home?

Home blood sugar (glucose) testing is an important part of controlling blood sugar. One important goal of diabetes treatment is to keep the blood glucose levels near the normal range of 70 to 120 mg/dl before meals and under 140 mg/dl at two hours after eating. Blood glucose levels are usually tested before and after meals, and at bedtime. The blood sugar level is typically determined by pricking a fingertip with a lancing device and applying the blood to a glucose meter, which reads the value. There are many meters on the market, for example, Accu-Check Advantage, One Touch Ultra, Sure Step and Freestyle. Each meter has its own advantages and disadvantages (some use less blood, some have a larger digital readout, some take a shorter time to give you results, etc). The test results are then used to help patients make adjustments in medications, diets, and physical activities.
There are some interesting developments in blood glucose monitoring. Currently, at least three continuous glucose sensors are being considered for approval in the United States (Dexcom, Medtronic and Navigator). The new continuous glucose sensor systems involve an implantable cannula placed just under the skin in the abdomen or in the arm. This cannula allows for frequent sampling of blood glucose levels. Attached to this is a transmitter that sends the data to a pager-like device. This device has a visual screen that allows the wearer to see, not only the current glucose reading, but also the graphic trends. In some devices, the rate of change of blood sugar is also shown. There are alarms for low and high sugar levels. Certain models will alarm if the rate of change indicates the wearer is at risk for dropping or rising blood glucose too rapidly. The Medtronic version is specifically designed to interface with their insulin pumps. However, at this time the patient still must manually approve any insulin dose (the pump cannot blindly respond to the glucose information it receives, it can only give a calculated suggestion as to whether the wearer should give insulin, and if so, how much). All of these devices need to be correlated to fingersticks for a few hours before they can function independently. The devices can then provide readings for 3-5 days.
Diabetes experts feel that these blood glucose monitoring devices give patients a significant amount of independence to manage their disease process; and they are a great tool for education as well. It is also important to remember that these devices can be used intermittently with fingersticks. For example, a well-controlled patient with diabetes can rely on fingerstick glucose checks a few times a day and do well. If they become ill, if they decide to embark on a new exercise regimen, if they change their diet and so on, they can use the sensor to supplement their fingerstick regimen, providing more information on how they are responding to new lifestyle changes or stressors. This kind of system takes us one step closer to closing the loop, and to the development of an artifical pancreas that senses insulin requirements based on glucose levels and the body's needs and releases insulin accordingly - the ultimate goal.

Hemoglobin A1c (A1c)

To explain what an A1c is, think in simple terms. Sugar sticks, and when it's around for a long time, it's harder to get it off. In the body, sugar sticks too, particularly to proteins. The red blood cells that circulate in the body live for about three months before they die off. When sugar sticks to these cells, it gives us an idea of how much sugar is around for the preceding three months. In most labs, the normal range is 4-5.9 %. In poorly controlled diabetes, its 8.0% or above, and in well controlled patients it's less than 7.0% (optimal is <6.5%).>

While there are no guidelines to use A1c as a screening tool, it gives a physician a good idea that someone is diabetic if the value is elevated. Right now, it is used as a standard tool to determine blood sugar control in patients known to have diabetes.

A1c(%)	Mean blood sugar (mg/dl)
6	135
7	170
8	205
9	240
10	275
11	310
12	345

The American Diabetes Association currently recommends an A1c goal of less than 7.0%. Other Groups such as the American Association of Clinical Endocrinologists feel that an A1c of <> Of interest, studies have shown that there is about a 10% decrease in relative risk for microvascular disease for every 1 % reduction in A1c. So, if a patient starts off with an A1c of 10.7 and drops to 8.2, though there are not yet at goal, they have managed to decrease their risk of microvascular complications by about 20%. The closer to normal the A1c, the lower the absolute risk for microvascular complications. Data also suggests that the risk of macrovascular disease decreases by about 24% for every 1% reduction in A1c values.
It should be mentioned here that there are a number of conditions in which an A1c value may not be accurate. For example, with significant anemia, the red blood cell count is low, and thus the A1c is falsely low as is similarly in cases of sickle cell disease and other hemoglobinopathies.

How is diabetes treated?

The major goal in treating diabetes is to minimize any elevation of blood sugar (glucose) without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with insulin,exercise and a diabetic diet. Type 2 diabetes is treated first with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, treatment with insulin is considered.

Adherence to a diabetic diet is an important aspect of controlling elevated blood sugar in patients with diabetes. The American Diabetes Association (ADA) has provided guidelines for a diabetic diet. The ADA diet is a balanced, nutritious diet that is low in fat, cholesterol, and simple sugars. The total daily calories are evenly divided into three meals. In the past two years, the ADA has lifted the absolute ban on simple sugars. Small amounts of simple sugars are allowed when consumed with a complex meal. For more, please read the Diabetic Diet article.
Weight reduction and exercise are important treatments for diabetes. Weight reduction and exercise increase the body's sensitivity to insulin, thus helping to control blood sugar elevations

Based on what is known, medications for type 2 diabetes are designed to:

1. Increase the insulin output by the pancreas.

2. Decrease the amount of glucose released from the liver.

3. Increase the sensitivity (response) of cells to insulin.

4. Decrease the absorption of carbohydrates from the intestine.

5. Slow emptying of the stomach to delay the presentation of carbohydrates for digestion and absorption in the small intestine.

When selecting therapy for type 2 diabetes, consideration should be given to:

1. The magnitude of change in blood sugar control that each medication will provide.

2. Other coexisting medical conditions (high blood pressure, high cholesterol, etc.)

3. Adverse effects of the therapy

4. Contraindications to therapy

5. Issues that may affect compliance (timing of medication, frequency of dosing)

6. Cost to the patient and the healthcare system

It's important to remember that if a drug can provide more than one benefit (lower blood sugar and have a beneficial effect on cholesterol, for example), it should be preferred. It's also important to bear in mind that the cost of drug therapy is relatively small compared to the cost of managing the long-term complications associated with poorly controlled diabetes.

Varying combinations of medications also are used to correct abnormally elevated levels of blood glucose in diabetes. As the list of medications continues to expand, treatment options for type 2 diabetes can be better tailored to meet an individuals needs. Not every patient with type 2 diabetes will benefit from every drug, and not every drug is suitable for each patient. Patients with type 2 diabetes should work closely with their physicians to achieve an approach that provides the greatest benefits while minimizing risks.

Patients with diabetes should never forget the importance of diet and exercise. The control of diabetes starts with a healthy lifestyle regardless of what medications are being used.

Treatment of diabetes with insulin

Insulin is the mainstay of treatment for patients with type 1 diabetes. Insulin is also important in type 2 diabetes when blood glucose levels cannot be controlled by diet, weight loss, exercise, and oral medications.

Ideally, insulin should be administered in a manner that mimics the natural pattern of insulin secretion by a healthy pancreas; however, the complex pattern of insulin secretion by the pancreas is difficult to duplicate. Still, adequate blood glucose control can be achieved with careful attention to diet, regular exercise, home blood glucose monitoring, and multiple insulin injections throughout the day.

In the past, the insulin was being derived from animal sources, particularly cows and pigs. Not only was there a problem with enough supply of insulin to meet the demand, but beef and pork insulin also had specific problems. Originating from animals, these types of insulin caused immune reactions in some people. Patients would become intolerant or resistant to animal insulin. With the acceleration of scientific research in the latter half of the twentieth century, beef and pork insulin were replaced by human insulin. In 1977, the gene for human insulin was cloned, and through modern technology, manufactured human insulin was made available. Human insulin is now widely used.

Insulin now comes in a variety of preparations that differ in the amount of time following injection until they begin to work and the duration of their action. Because of these differences, combinations of insulin are often used to allow for a more tailored regimen of blood sugar control. The table below lists the most common types of insulin currently in use in the U.S. and their specific properties.

Name of Insulin	Onset of Action	Peak Effect After Injection
Humalog and Novolog//Very Short Acting	5-15 minutes	30-60 minutes
Regular/Short Acting	30 minutes	2-5 hours
NPH/Intermediate Acting	1-2.5 hours	8-14 hours
Lente/Intermediate Acting	1-2.5 hours	8-12 hours
Ultra Lente/Long Acting	4-6 hours	10-18 hours
Lantus	2-3 hours	Stable from 2-3 hours to @20 hours
Detemir	3-4 hours	Dose dependent (longer acting at higher doses)
Combinations - 75/25, 70/30, 50/50	30 minutes	7-12 hours

For example, a patient may take an injection of Lantus in the morning and evening to provide a baseline of insulin throughout a 24-hour period. In addition, the same patient may take an injection of Humalog just before meals to cover the increase in carbohydrate load after eating.