diabetes mellitus

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A disease in which glucose (sugar) is not adequately taken up from the bloodstream by the cells of the body and therefore cannot be metabolized to produce energy or stored in the liver. It is caused by an abnormality in the synthesis and secretion of the hormone insulin. Diabetes mellitus is characterized by high concentrations of glucose in the blood (hyperglycaemia) and in the urine, with symptoms of thirst, loss of weight, tiredness, and an excessive production of urine.

People affected with insulin-dependent (or type I) diabetes mellitus have little or no ability to produce the hormone and depend on daily injections of insulin. This type of diabetes can also be referred to as juvenile-onset diabetes because it usually starts during childhood or adolescence. The dosage of insulin must be carefully controlled and matched to the dietary intake of glucose. If cells receive insufficient glucose, fats may be used as an alternative source of energy, which can lead to alteration of the acidity of the blood, the accumulation of ketones (formed when fats are metabolized) in the bloodstream (ketoacidosis), and eventually to diabetic coma. Type II (noninsulin-dependent or maturity-onset) diabetes mellitus develops in adults, usually over 40 years old, because of a decrease in the production of natural insulin, although the pancreas still functions to some extent; alternatively, the body becomes resistant to the effect of insulin. This condition occurs more often in people who are overweight; it is usually treated by diet, weight reduction, and oral hypoglycaemic drugs, but some patients may need insulin instead.

All people with diabetes, regardless of which type, must pay attention to their diet, in which the amount of carbohydrate should be carefully controlled to suit their body's needs, and be aware of the importance of monitoring blood glucose concentrations. Very low blood glucose (hypoglycaemia) may be caused by excessive dosage of insulin or some oral antidiabetic drugs or by missing a meal. Good control of blood sugar is necessary to prevent such long-term consequences of diabetes as atherosclerosis (giving rise to heart disease), poor circulation in the extremities (causing foot ulcers), impairment of eyesight, and kidney damage.

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Definition

Diabetes mellitus is a chronic disease in which the body is not able to correctly process glucose for cell energy due to either an insufficient amount of the hormone insulin or a physical resistance to the insulin the body does produce. Without proper treatment through medication and/or lifestyle changes, the high blood glucose (or blood sugar) levels caused by diabetes can cause long-term damage to organ systems throughout the body.

Description

There are three types of diabetes mellitus: type 1 (also called juvenile diabetes or insulin-dependent diabetes), type 2 (also called adult-onset diabetes), and gestational diabetes. While type 2 is the most prevalent, consisting of 90 to 95 percent of diabetes patients in the United States, type 1 diabetes is more common in children. Gestational diabetes occurs in pregnancy and resolves at birth.

Every cell in the human body needs energy in order to function. The body's primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (primarily sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for any cells that need it. However, glucose requires insulin in order to be processed for cellular energy.

Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin bonds to a receptor site on the outside of a cell. It acts like a key to open a doorway into the cell through which glucose can enter. When there is not enough insulin produced (as is the case with type 1 diabetes) or when the doorway no longer recognizes the insulin key (which happens in type 2 and gestational diabetes), glucose stays in the bloodstream rather entering the cells. The high blood glucose, or blood sugar, levels that result are known as hyperglycemia.

Type 1 Diabetes

Type 1 diabetes occurs when the beta cells of the pancreas are damaged and stop producing the hormone insulin. While the exact cause of this cell damage is not completely understood, it is thought to be a combination of environmental and autoimmune factors. Despite the name juvenile diabetes, type 1 diabetes can be diagnosed at any stage of life, although diagnosis in childhood through young adulthood is most common.

Children who develop type 1 diabetes must eventually take regular insulin injections to keep blood glucose levels under control and do the job of the pancreas. Regular home testing of blood sugar levels is also important to make sure that the treatment is working effectively and to avoid a diabetic emergency such as hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar).

Type 2 Diabetes

The hallmark characteristic of type 2 diabetes is insulin resistance. The pancreas typically produces enough insulin (often too much insulin); however, cells are resistant to the insulin and it may not work as effectively. Type 2 is the most common form of diabetes, and most individuals with the disease are adults. However, children and adolescents can develop type 2 diabetes too, particularly if they are overweight and have a history of type 2 diabetes in their family.

Type 2 diabetes is treated with diet, exercise, and in some cases, oral medication and/or insulin. Self-monitoring of blood glucose levels is also important to assess how well treatment is working.

Demographics

An estimated 18.2 million Americans live with diabetes, and over 5 million of those remain undiagnosed. Up to 95 percent of diabetes patients in the United States have type 2 diabetes; the vast majority of Americans with diabetes are over 20 years of age. Those under 20 represent only 206,000 of the total cases of diabetes in the United States.

While type 2 diabetes is a growing problem among American youth due to climbing obesity rates and more sedentary lifestyles, type 1 diabetes is more prevalent in children and adolescents. An estimated one in 400 to 500 children have type 1 diabetes.

The American Diabetes Association reports that in 2002, diabetes cost Americans an estimated $132 billion in direct medical costs and indirect expenses such as lost productivity and disability payments.

Causes and Symptoms

The causes of diabetes are not completely understood; however, there seem to be both genetic and environmental factors involved in the development of both type 1 and type 2 diabetes, meaning that a person may have a genetic predisposition to developing diabetes, but it takes an environmental factor such as a viral infection or excessive weight gain to actually make the disease surface.

Research has shown that some people who develop diabetes have common genetic markers. In type 1 diabetes, the immune system, the body's defense system against infection, is believed to be triggered by a virus or another microorganism that causes an autoimmune reaction that eventually destroys the insulin-producing cells (i.e., beta cells) in the pancreas. Up to 90 percent of cases of type 1 diabetes are the autoimmune subtype, sometimes called type 1A or immune-mediated diabetes.

The other subtype of type 1 diabetes is called idiopathic, or type 1B diabetes. People who have idiopathic type 1 diabetes also experience beta cell destruction, but it is due to a chromosomal abnormality or an unknown cause rather than any autoimmune process. Only tests for islet cell antibodies and other autoimmune markers can differentiate between the two subtypes, and because testing can be costly and treatment for both is the same (i.e., insulin), a physician may not necessarily order tests for autoimmunity.

Finally, damage caused by diseases of the pancreas (such as pancreatitis), endocrine disorders (e.g., endocrine tumors), and drugs or toxins can also destroy beta cell function.

In type 2 diabetes, family history, age, weight, activity level, and ethnic background can all play a role in the genesis of the disease. Individuals who are at high risk of developing type 2 diabetes mellitus include the following groups:

• people who are overweight or obese (more than 20 percent above their ideal body weight)
• people who have a parent or sibling with type 2 diabetes
• those who belong to a high-risk ethnic population (African-American, Native American, Asian-American, Hispanic, or Pacific Islander)
• people who live a sedentary lifestyle (i.e., exercise less than three times a week)
• women who have been diagnosed with gestational diabetes or have delivered a baby weighing more than 9 lbs (4 kg)
• people with high blood pressure (140/90 mmHg or above)
• people with high density lipoprotein cholesterol (HDL, or "good" cholesterol) level less than or equal to 35 mg/dl and/or a triglyceride level greater than or equal to 250 mg/dl

Several common medications can cause chronic high blood sugar levels and/or promote insulin resistance. These include atypical antipsychotics, beta blockers, corticosteroids, diuretics, estrogens, lithium, protease inhibitors, niacin, and some thyroid preparations.

Both type 1 and type 2 diabetes share similar symptoms caused by chronically high blood glucose levels.

Symptoms of both type 1 and type 2 diabetes include:

• excessive thirst
• frequent urination
• weight loss
• increased appetite
• unexplained fatigue
• slow healing cuts, bruises, and wounds
• frequent or lingering infections (e.g., urinary tract infection)
• mood swings and irritability
• blurred vision
• headache
• high blood pressure
• dry and itchy skin
• tingling, numbness, or burning in hands or feet

Symptoms of diabetes can develop suddenly (over days or weeks) in previously healthy children or adolescents, or can develop gradually, particularly in the case of type 2 diabetes.

Children and adolescents sometimes develop a condition known as diabetic ketoacidosis (DKA) at the time of their diagnosis. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins for energy. When blood sugars are high (i.e., over 249 mg/dl, or 13.8 mmol/L) for prolonged periods of time, ketones build up in the bloodstream to dangerous levels. Symptoms of DKA include abdominal pain, excessive thirst, nausea and vomiting, rapid breathing, extreme lethargy, and drowsiness. Patients with ketoacidosis will also have a fruity or sweet breath odor. Left untreated, this condition can lead to coma and has the potential to be fatal. DKA is more common in people with type 1 diabetes, although it can occur in type 2 diabetes as well.

Symptoms of type 2 diabetes can begin so gradually that a person may not know that he or she has it. It is not unusual for type 2 diabetes to be detected while a patient is seeing a doctor about another health concern that is actually being caused by the yet undiagnosed diabetes, such as heart disease, chronic infections (e.g., urinary tract infections, yeast infections), blurred vision, numbness in the feet and legs, or slow-healing wounds.

When to Call the Doctor

If left untreated, diabetes is a life-threatening condition. Any child displaying symptoms of diabetes should be taken to a doctor or emergency care facility for evaluation immediately.

Diagnosis

Diagnosis of diabetes is suspected based on symptoms and confirmed by blood tests that measure the level of glucose in blood plasma. Dipstick or reagent test strips that measure glucose in the urine can only detect glucose levels above 180 mg/dl and are non-specific, so they are not useful in the diagnosis of diabetes. However, they are a non-invasive way to obtain a fast and simple reading that a physician might use as a basis for ordering further diagnostic blood tests for diabetes, particularly in children.

Blood tests are the gold standard for the diagnosis of both type 1 and type 2 diabetes in children and adults. The American Diabetes Association recommends that a random plasma glucose, fasting plasma glucose, or oral glucose tolerance test (OGTT) be used for diagnosis of diabetes. The OGTT is commonly used as a screening measure for gestational diabetes. Fasting plasma glucose is the test of choice unless a child is exhibiting classic symptoms of diabetes, in which case a random (or casual) plasma glucose test is acceptable.

Unless hyperglycemia is obvious (e.g., blood glucose levels are extremely high or the child experiences DKA), the fasting or random plasma glucose test should be confirmed on a subsequent day with a repeat test.

Fasting Plasma Glucose Test

Blood is drawn from a vein in the child's arm following an eight-hour fast (i.e., no food or drink), usually in the morning before breakfast. The red blood cells are separated from the sample and the amount of glucose is measured in the remaining plasma. A fasting plasma glucose level of 126 mg/dl (7.0 mmol/l) or higher indicates diabetes (with a confirming retest on a subsequent day).

Random Plasma Glucose Test

Blood is drawn at any time of day, regardless of whether the patient has eaten. A random plasma glucose concentration of 200 mg/dl (11.1 mmol/l) or higher in the presence of symptoms indicates diabetes.

Oral Glucose Tolerance Test

Blood samples are taken both before and several times after a patient drinks 75 grams of a glucose-based beverage. If plasma glucose levels taken two hours after the glucose drink is consumed are 200 mg/dl (11.1 mmol/L) or higher, the test is diagnostic of diabetes (and should be confirmed on a subsequent day if possible).

Although the same diagnostic blood tests are used for both types of diabetes, whether a child is diagnosed as type 1 or type 2 can typically be determined based on her personal and medical history. The majority of children diagnosed in childhood are type 1, but if blood test results indicate prediabetes and a child is significantly overweight and has a history of type 2 diabetes in her family, type 2 is a possibility.

Further blood tests can help to differentiate between type 1 and type 2 when the diagnosis is unclear. One of these is an assessment of c-peptide levels, a protein released along with insulin that can help a physician determine whether or not a patient is producing sufficient amounts of insulin. The other is a GAD (Glutamic Acid Decarboxylase) autoantibody test. The presence of GAD autoantibodies may indicate the beginning of the autoimmune process that destroys pancreatic beta cells.

Treatment

Children with type 1 diabetes must take insulin injections or infusions. Their dosage needs may change over time. Sometimes children will experience a decreased need for insulin once blood sugars are brought under control following diagnosis. Their insulin needs may go down, and in some cases, they can stop taking injections for a time. This phenomenon, known as the honeymoon period, can last anywhere from a few days to months.

Children with diabetes and their parents should learn to operate a home blood glucose monitor. Home testing can prevent dangerous highs and lows and help parents and children understand how food and exercise impact blood sugar levels. Blood glucose levels taken before meals are also used to calculate dose size of insulin. A small needle or lancet is used to prick the finger or alternate site and a drop of blood is collected on a test strip that is inserted into a monitor. The monitor then calculates and displays the blood glucose reading on a screen. Although individual blood glucose targets should be determined by a medical professional in light of a child's medical history, the general goal is to keep them as close to normal (i.e., 90 to 130 mg/dl or 5 to 7.2 mmol/L before meals) as possible.

Insulin

Children with type 1 diabetes need daily injections of insulin to help their bodies use glucose. The amount and type of insulin required depends on the height, weight, age, food intake, and activity level of the individual diabetic patient. Some patients with type 2 diabetes may also need to use insulin injections if their diabetes cannot be controlled with diet, exercise, and oral medication. Injections are given subcutaneously, that is, just under the skin, using a small needle and syringe, an insulin pen injector, an insulin infusion pump, or a jet injector device. Injection sites can be anywhere on the body where there is a layer of fat available, including the upper arm, abdomen, or upper thigh.

Insulin may be given as an injection of a single dose of one type of insulin once a day, or different types of insulin can be mixed and given in one dose or split into two or more doses during a day. Patients who require multiple injections over the course of a day may be able to use an insulin pump that administers small doses of insulin on demand. The small battery-operated pump is worn outside the body and is connected to a cannula (a thin, flexible plastic tube) that is inserted into the abdomen called an insertion set. Pumps are programmed to infuse a small, steady infusion of insulin (called a basal dose) throughout the day, and larger doses (called boluses) before meals. Because of the basal infusion, pumps can offer many children much tighter control over their blood glucose levels and more flexibility with their diet than insulin shots afford them.

Regular insulin is fast-acting and starts to work within 15 to 30 minutes, with its peak glucose-lowering effect about two hours after it is injected. Its effects last for about four to six hours. NPH (neutral protamine Hagedorn) and Lente insulin are intermediate-acting, starting to work within one to three hours and lasting up to 18 to 26 hours. Ultra-lente is a long-acting form of insulin that starts to work within four to eight hours and lasts 28 to 36 hours. Peakless, or basal-action insulin (insulin glargine, or Lantus) starts working in 15 minutes and has a duration of between 18 and 26 hours.

Nutritional Concerns

Because dietary carbohydrates are the primary source of glucose for the body (the other source being the liver), it is very important that children with diabetes learn to read labels and be aware of the amount of carbohydrates in the foods they eat. Children and their parents are usually advised to consult a registered dietitian (RD) to create an individualized, easy to manage food plan that fits their family's health and lifestyle needs. A well-balanced, nutritious diet provides approximately 50 to 60 percent of calories from carbohydrates, approximately 10 to 20 percent of calories from protein, and less than 30 percent of calories from fat. The number of calories required depends on age, weight, and activity level. An RD can also teach the family how to use either the dietary exchange lists or carbohydrate counting system to monitor food intake.

Each food exchange contains a known amount of calories in the form of protein, fat, or carbohydrate. A patient's diet plan will consist of a certain number of exchanges from each food category (meat or protein, fruits, breads and starches, vegetables, and fats) to be eaten at meal times and as snacks. Patients have flexibility in choosing which foods they eat as long as they stick with the number of exchanges prescribed by their RD based on their caloric requirements.

Carbohydrate counting involves totaling the grams of carbohydrates in the foods your child eats to ensure the child does not exceed her goal for the day. In the simple-carb counting method, one carbohydrate choice or unit equals 15 grams of carbohydrates (which is equivalent to one starch or fruit exchange in the exchange method). The number of carb choices allowed daily is based on caloric requirements.

Children with type 1 diabetes who use fast-acting insulin before meals may find that carb counting gives them tighter control of their blood glucose levels, since they can compute the number of insulin units based on both their carbohydrate intake (called the carbohydrate to insulin ratio) and before-meal blood glucose readings.

Dietary changes and moderate exercise are usually the first treatments implemented in type 2 diabetes. Weight loss may be an important goal in helping overweight children and adolescents control their blood sugar levels. Exercise helps keep blood glucose levels down and has other health benefits, as well.

Oral Medications

Children with type 2 diabetes may be prescribed oral medications if they are unable to keep their blood glucose levels under control with dietary and exercise measures. As of 2004, metformin was the only oral medication approved by the U.S. FDA for use in children over age ten. Metformin (trade name Glucophage) is in the biguanide class of drugs and works by reducing the amount of glucose the liver produces and the amount of circulating insulin in the body. Other adult type 2 diabetes medications, such as sulfonylureas and meglitinide drugs, which work by increasing insulin production, may be prescribed off-label for pediatric use.

Transplants

Transplantation of a healthy pancreas into a patient with type 1 diabetes can eliminate the need for insulin injections; however, this transplant is typically done only if a kidney transplant is performed at the same time. Although a pancreas transplant is possible, it is not clear if the potential benefits outweigh the risks of the surgery and life-long drug therapy needed to prevent organ rejection, particularly in the case of children.

A second type of transplant procedure, as of 2004 in experimental clinical trials and not available to children, is an islet cell transplant. In this type of treatment, insulin-producing islet cells are harvested from a donor pancreas and injected into the liver of a recipient, where they attach to new blood vessels and (ideally) begin producing insulin. A lifetime regimen of immunosuppressive drugs is required to prevent rejection of the transplanted cells.

Prognosis

As of 2004 diabetes is a chronic and incurable disease. While stem cell research holds great promise for future therapies and potential cures, as of the early 2000s the best hope for keeping children well with diabetes and avoiding long-term complications is maintaining good blood glucose control. The landmark Diabetes Control and Complications Trial (DCCT) found that patients with type 1 diabetes who kept their blood sugar levels as close to normal as possible reduced their risk for developing diabetic eye disease by 76 percent, for diabetic kidney disease by 50 percent, and for diabetic neuropathy by 60 percent.

Diabetes and its related complications was the sixth leading cause of death in 2000. According to the National Institutes of Health, cardiovascular, or heart and blood vessel disease, is the leading cause of diabetes-related death. Uncontrolled diabetes is a leading cause of blindness, end-stage renal disease, and limb amputations. Eye problems including cataracts, glaucoma, and diabetic retinopathy also are more common in people with diabetes.

Diabetic neuropathy is the result of nerve damage caused by uncontrolled diabetes. Autonomic neuropathy affects the autonomic nervous system and can cause gastroparesis (nerve damage of the stomach), neurogenic bladder (nerve damage of the urinary bladder), and a host of other problems with involuntary functions of the nervous system.

In peripheral neuropathy (PN), nerve damage in the extremities (e.g., the legs and feet) causes numbness, pain, and burning. Diabetic foot ulcers are a particular problem since frequently the patient does not feel the pain of a blister, callous, or other minor injury. Poor blood circulation in the legs and feet contribute to delayed wound healing. The inability to sense pain along with the complications of delayed wound healing can result in minor injuries, blisters, or calluses becoming infected and difficult to treat. The most serious consequence of this condition is the potential for amputation of toes, feet, or legs due to severe infection.

Diabetic kidney disease is another common complications of diabetes. Long-term complications may include the need for kidney dialysis or a kidney transplant due to kidney failure. Diabetes is the number one cause of chronic kidney failure in America.

Children and adults with the autoimmune form of type 1 diabetes are also at greater risk for other autoimmune disorders, including thyroid disease, celiac sprue (sometimes called gluten intolerance), autoimmune hepatitis, myasthenia gravis, and pernicious anemia.

Prevention

As of 2004 research continues on diabetes prevention and improved detection of those at risk for developing diabetes. While the onset of type 1 diabetes is unpredictable, the risk of developing type 2 diabetes may be reduced by maintaining ideal weight and exercising regularly. Both physical and emotional stress can cause increases in blood glucose levels, so getting regular immunizations and well-child check-ups, practicing good sleep and hygiene habits, encouraging emotional and social growth, and maintaining a stress-controlled lifestyle is important for children with type 1 or type 2 diabetes.

Parental Concerns

Parents of children with diabetes must work with their child's teachers and school administrators to ensure that their child is able to test her blood sugars regularly, take insulin as needed, and have access to food or drink to treat a low. Someone at school should also be trained in how to administer a glucagon injection, an emergency treatment for a hypoglycemic episode when a child loses consciousness.

Section 504 of the Rehabilitation Act of 1973 enables parents to develop both a Section 504 plan (which describes a child's medical needs) and an individualized education plan (IEP) (which describes what special accommodations a child requires to address those needs). An IEP should cover such issues as blood glucose monitoring, dietary plans, and treating highs and lows. If school staff has little to no experience with diabetes, bringing in a certified diabetes educator (CDE) to offer basic training may be useful.

Children with diabetes can lead an active life and enjoy most of the activities and foods their peers do, with a few precautions to avoid blood sugar highs or lows. A certified diabetes educator that has experience working with children can help them understand the importance of regular testing as well as methods for minimizing discomfort. Diabetes summer camps, where children can learn about diabetes care in the company of peers and counselors who also live with the disease, may be useful from both a health and a social standpoint. In addition, peer support groups can sometimes help children come to terms with their diabetes.

Hypoglycemia, or low blood sugar, can be caused by too much insulin, too little food (or eating too late to coincide with the action of the insulin), alcohol consumption, or increased exercise. A child with symptoms of hypoglycemia may be hungry, cranky, confused, and tired. The patient may become sweaty and shaky. Left untreated, a child can lose consciousness or have a seizure. This condition is sometimes called an insulin reaction and should be treated by giving the patient something sweet to eat or drink like candy, juice, glucose gel, or another high sugar snack. A child who loses consciousness due to a low should never be given food or drink due to the risk of choking. In these cases, a glucagon injection should be administered and the child should be taken to the nearest emergency care facility.

While exercise can lower blood glucose levels, children with diabetes can and do excel in sports. Proper hydration, frequent testing, and a before-game or practice snack can prevent hypoglycemia. Coaches or another onsite adult should be aware of a child's medical condition and be prepared to treat a hypoglycemic attack if necessary.

The other potential danger to a child with diabetes—diabetic ketoacidosis—is uncommon and most likely to occur prior to a diagnosis. It may also happen if insulin is discontinued or if the body is under stress due to illness or injury. Ketones in the urine can be detected using dipstick tests (e.g., Ketostix), or detected using a home ketone blood monitor. Early detection facilitates early treatment and can prevent full-blown DKA.

Because the symptoms of DKA can mimic the flu, and the flu can increase blood sugar levels, a child who comes down with a flu-like illness should be monitored closely and tested regularly. An increase in insulin may also be necessary; parents of children with diabetes should talk with their pediatrician about a sick day plan for their child before they need it.

See also Hypoglycemia.

Resources

Books

The American Diabetes Association Complete Guide to Diabetes, 3rd ed. Alexandria, VA: American Diabetes Association, 2002.

Brackenridge, Betty, and Richard Rubin. Sweet Kids: How to Balance Diabetes Control and Good Nutrition with Family Peace, 2nd ed. Alexandria, VA: American Diabetes Association, 2002.

Ford-Martin, Paula, with Ian Blumer. The Everything Diabetes Book. Avon, MA: Adams Media, 2004.

Organizations

American Diabetes Association. 1701 North Beauregard St., Alexandria, VA 22311. Web site: www.diabetes.org.

American Dietetic Association. 216 W. Jackson Blvd., Chicago, IL 60606–6995. Web site: www.eatright.org.

Children with Diabetes. 5689 Chancery Place, Hamilton, OH 45011. Web site: www.childrenwithdiabetes.org.

Juvenile Diabetes Research Foundation. 120 Wall St., 19th Floor, New York, NY 10005. Web site: www.jdrf.org.

National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892–3560. Web site: www.niddk.nih.gov/health/diabetes/ndic.htm.

Web Sites

"2004 Clinical Practice Recommendations." Diabetes Care, January, 2004. Available online at (accessed December 26, 2004).

Ford-Martin, Paula. "About Diabetes" Available online at (accessed December 26, 2004).

Mendosa, David. David Mendosa's Diabetes Directory. Available online at www.mendosa.com/diabetes.htm (accessed December 26, 2004).

[Article by: Paula Ford-Martin Altha Roberts Edgren Teresa G. Odle]

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The term "diabetes mellitus" represents a group of conditions characterized by abnormally high blood glucose levels (hyperglycemia). In 1997, nearly 16 million people in the United States had diabetes; approximately 10.3 million were diagnosed with the conditions, while an estimated 5.4 million were undiagnosed. Diabetes may be complicated by uncontrolled hyperglycemia, and treated diabetes may be complicated by abnormally low blood glucose levels (hypoglycemia). Maternal diabetes is associated with an increased incidence of major birth defects. Over time, diabetes may cause complications involving the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy). Diabetes is also associated with an increased incidence of cardiovascular disease, including stroke, heart attack, and peripheral vascular disease. In the United States today, diabetes is a leading cause of birth defects, blindness, kidney failure, and nontraumatic leg amputations. It is also a major contributor to cardiovascular disease. Diabetes is the seventh leading cause of death in the United States, and medical care for people with diabetes is estimated to cost over $100 billion per year.

When diabetes is associated with marked hyperglycemia, it produces characteristic symptoms and signs; particularly increased thirst (polydipsia), increased urination (polyuria), and unexplained weight loss. At other times, hyperglycemia sufficient to cause changes in the eyes, kidneys, and nerves, and to increase the risk of cardiovascular disease, may be present without clinical symptoms. During this asymptomatic period, an abnormality in glucose metabolism may be demonstrated by measuring fasting venous glucose or venous glucose after an oral glucose challenge.

Diagnosis

When a patient is symptomatic and the plasma glucose is unequivocally elevated, a diagnosis of diabetes presents no difficulty. When a patient is without clinical symptoms, a diagnosis of diabetes is more difficult. According to a 1997 American Diabetes Association (ADA) report, there are three ways to diagnose diabetes (see Table 1). All require measurement of venous plasma glucose, and each must be confirmed on a subsequent day by any one of the three methods. In general, the oral glucose tolerance test is not recommended for routine clinical use and is performed only in patients with elevated but nondiagnostic fasting plasma-glucose levels with a high index of suspicion for diabetes.

Classification

Once a diagnosis of diabetes mellitus is established, it is necessary to differentiate the various forms of the syndrome. Prior to 1979, diabetes was

Table 1

Criteria for the Three Methods Diagnosis of Diabetes Mellitus in Nonpregnant Adults
* In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day. The third measure (OGTT) is not recommended for routine clinical use.
SOURCE: Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997). Diabetes Care 20:1183-1197.
Symptoms of diabetes plus casual plasma glucose concentration ≥200 mg/dL (11.1 mmol/L).* Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. Fasting Plasma Glucose ≥ 126 mg/dL (7.0 mmol/L).* Fasting is defined as no caloric intake for at least 8 hours. 2-hour Plasma Glucose ≥ 200 mg/dL (11.1 mmol/L) during an Oral Glucose Tolerance Test (OGTT).* The test should be performed using a glucose load containing the equivalent of 75 g. anhydrous glucose dissolved in water.

classified on the basis of age at diagnosis as either juvenile-onset diabetes mellitus (JODM) or adult-onset diabetes mellitus (AODM). In the late 1970s and early 1980s, a new classification system recognized two major forms of diabetes: insulin-dependent diabetes mellitus (IDDM or type I diabetes) and non-insulin-dependent diabetes mellitus (NIDDM or type II diabetes). In 1997, the American Diabetes Association recommended modifications to this classification system that eliminated the terms "insulin-dependent diabetes mellitus" and "non-insulin-dependent diabetes mellitus" and their acronyms. The terms "type 1" and "type 2" were retained, with Arabic numerals replacing the Roman numerals. Other specific types of diabetes were also recognized.

Type 1 diabetes is caused by pancreatic beta cell (B-cell) destruction. Immune-mediated type 1 diabetes results from cell-mediated autoimmune destruction of the B-cells of the pancreatic islets. This type of diabetes also has strong genetic or human leukocyte antigen (HLA) associations that can be either predisposing or protective. Another form of type 1 diabetes, termed "idiopathic" type 1 diabetes, is strongly inherited but lacks immunologic evidence for B-cell autoimmunity and is not HLA-associated. Most patients with

Table 2

Incidence of Diagnosed Diabetes per 1,000 Population by Age, United States, 1994.
Age Group
0–4	45–64	65+	Total
SOURCE: Centers for Disease Control and Prevention (1997). Diabetes Surveillance, 1997. Atlanta, GA: CDC.
1.59	7.20	8.84	3.61

idiopathic type 1 diabetes are of African or Asian descent.

Type 1 diabetes accounts for approximately 5 percent of diagnosed diabetes in the United States—approximately 500,000 Americans have type 1 diabetes. Type 1 diabetes commonly occurs in childhood and adolescence, but it can occur at any age. Patients with type 1 diabetes are prone to ketoacidosis (decompensated diabetes with hyperglycemia and presence of abnormal acids [ketones] in the blood). Many affected patients have no family history of diabetes. Although most patients with type 1 diabetes are lean when they are diagnosed, the presence of obesity is not incompatible with the diagnosis.

Type 2 diabetes is characterized by both impairment of insulin secretion and defects in insulin action. It is often unclear which abnormality is the primary cause of hyperglycemia. Although patients with this type of diabetes may have insulin levels that appear normal or elevated, insulin levels are always low relative to the elevated plasma glucose levels. Thus, insulin secretion is defective in these patients and insufficient to compensate for the degree of insulin resistance. Although the specific origin of type 2 diabetes is not known, autoimmune destruction of B-cells does not occur. Although type 2 diabetes is associated with a strong genetic predisposition, the genetics of this form of diabetes are complex and not clearly defined.

Type 2 diabetes accounts for approximately 95 percent of diagnosed diabetes in the United States (9.8 million cases), and for the vast majority of the cases of undiagnosed diabetes. The risk of type 2 diabetes increases with age, obesity, and physical inactivity. As such, it is often regarded as a disease associated with a modern Western lifestyle. Type 2 diabetes occurs more frequently in women with prior gestational diabetes and in individuals with hypertension and dyslipidemia. Affected patients often have a family history of diabetes. Type 2 diabetes is more common in African Americans, Hispanic Americans, and Native Americans than in non-Hispanic white Americans. Ketoacidosis seldom occurs spontaneously in type 2 diabetes, but it may arise in association with the stress of another illness. Approximately 70 percent of patients with type 2 diabetes are obese.

Treatment

Large, prospective, randomized, controlled clinical trials in both type 1 and type 2 diabetes have demonstrated that normal or near-normal blood glucose control can delay or prevent the development of major birth defects and the development and progression of complications affecting the eyes, kidneys, and nerves. Accordingly, the goals for management for both type 1 and type 2 diabetes are to achieve glucose levels as close to the nondiabetic range as possible while minimizing the side-effects of treatment (hypoglycemia and weight gain).

In nondiabetic subjects, blood glucose levels are between 70 and 90 mg/dl (milligrams per deciliter) in the fasting state and rise to 120 to 140 mg/dl one to two hours after meals. These values reflect normal glucose tolerance. Average glucose levels may be assessed by measurement of glycosylated hemoglobin (hemoglobin A1c), is a measure of the average blood glucose level over the previous two to four months. In nondiabetic subjects, hemoglobin A1c is generally less than 6.1 percent, and in poorly controlled diabetic subjects, it may rise to 12 percent or higher.

In general, the goals of treatment are to achieve blood glucose and hemoglobin A1c levels as close to the nondiabetic range as possible with diet, physical activity, and medications.

Diet. In type 1 diabetes, diet is designed to provide adequate nutrients for growth and development and for the maintenance of ideal body weight. The recommended diet includes approximately 20 percent of daily calories from protein, 30 percent from fat, and 50 percent from complex carbohydrates. Simple sugars are limited to prevent excessive glucose excursions, and carbohydrate content is distributed into regular meals and

Table 3

Prevalence of diagnosed diabetes per 1,000 population by age, sex, and race, United States, 1994
Age Group
Population	0–44	45–64	65–74	75+	Total
From Centers for Disease Control and Prevention. Diabetes Surveillance, 1997. Atlanta, GA. U.S. Department of Health and Human Services, 1997.
white males	7.8	57.7	96.0	106.8	28.4
black males	10.6	120.8	171.8	120.6	35.9
white females	7.9	51.9	97.2	89.2	30.5
black females	12.1	134.5	171.8	173.5	47.9
Total	8.3	62.2	101.5	103.3	30.8

snacks so that a similar quantity of carbohydrate is consumed at approximately the same time each day.

In type 2 diabetes, caloric content is adjusted to achieve and maintain an ideal body weight or, in those who are obese, to produce gradual weight loss or at least weight maintenance. Dietary composition may also be adjusted in light of intercurrent conditions. For example, sodium may be restricted for patients with hypertension, and both total fat and saturated fat may be restricted for those with high cholesterol.

Exercise. Exercise lowers blood glucose and improves glucose tolerance in diabetics. Other benefits of exercise are reductions in LDL cholesterol and triglycerides levels, and improvements in HDL cholesterol, improvements in blood pressure, improved cardiovascular fitness, and an increased sense of well-being and quality of life. Because exercise may potentiate the hypoglycemic effect of injected insulin and may, paradoxically, result in elevated blood glucose levels and the rapid development of ketosis in type 1 diabetic patients in poor metabolic control, the goal of management in type 1 diabetes is to permit people to enjoy and participate safely in physical and sport activities. In type 2 diabetes, exercise is frequently prescribed as an adjunct to reduced-calorie diets for weight reduction and to improve insulin resistance.

Medications. Because patients with type 1 diabetes are absolutely insulin deficient, treatment requires insulin injections. Although one or two injections per day are often adequate to prevent symptoms of hyperglycemia, intensive therapy employing three or four insulin injections per day, or continuous subcutaneous insulin infusion, may be necessary to achieve near-normal glucose control.

Both oral medications and injected insulin are used for the treatment of type 2 diabetes. Four groups of oral agents are currently available: insulin secretagogues, which enhance nutrient-stimulated insulin secretion; the biguanides, which suppress abnormal glucose production by the liver; the thiazolidinediones, which reduce insulin resistance at the level of muscle and fat; and the alpha-glucosidase inhibitors, which slow the breakdown and absorption of carbohydrates and reduce postprandial glucose excursions. To the extent that these four groups of oral medications have different mechanisms of action, they can be used clinically in combination. When oral agents are ineffective in controlling hyperglycemia or achieving glycemic goals, insulin is added or substituted.

Monitoring

Self-monitoring of blood glucose is integral to modern diabetes therapy. A lancet is used to obtain a small drop of blood, which is placed on a reagent strip and inserted in a small battery-powered meter. The meter reports the blood glucose level in less than a minute. Results of self-monitoring of blood glucose are used to guide adjustments in diet, exercise, and medications, for the monitoring and treatment of hypoglycemia, and in the home management of intercurrent illness.

Incidence and Prevalence

The number of people developing diabetes and the number of people with diabetes are increasing worldwide. In 2000, it was estimated that 154 million persons, or 4.2 percent of the world's population, twenty years of age and older had diabetes. By the year 2025, it is estimated that nearly 300 million persons, or 5.4 percent of the world's population, twenty years of age and older will have diabetes. The major part of this increase will occur in developing countries due to the aging of the population and increasing urbanization (associated with increased body weight and decreased physical activity).

In 1994, there were 939,000 Americans newly diagnosed with diabetes, with a disproportionate number among the elderly and minority populations. The incidence of diagnosed diabetes was3.61 cases per 1,000 persons per year in 1994 (see Table 2).

In 1994, about 8 million persons in the United States (3.1 percent of the population) reported that they had diabetes. The prevalence of diagnosed diabetes increases with age (see Table 3).

Mortality

Diabetes is the seventh leading cause of deaths in the United States. The highest death rates due to diabetes are observed in older Americans and in minority populations. Death certificates underestimate diabetes mortality because of underreporting of diabetes. Only about 10 percent of people with diabetes who die have diabetes listed as the underlying cause of death on their death certificates, and only about 40 percent have it listed anywhere on their death certificates. Diabetes was the underlying cause of death for approximately 57,000 Americans in 1994, and diabetes was recorded on the death certificate of approximately 182,000 Americans. In 1994, black women had the highest death rates due to diabetes, followed by white women and men. That same year, 44 percent of all diabetes-related deaths (80,000 deaths) had cardiovascular disease listed as the underlying cause. Of these deaths, approximately 60 percent were caused by ischemic heart disease and 15 percent by stroke.

Complications and Comorbidities Associated With Diabetes

Diabetic Ketoacidosis (DKA). Ketoacidosis is an acute metabolic complication of diabetes associated with hyperglycemia, nausea, vomiting, abdominal pain, dehydration, ketonemia, and acidosis. In 1994, DKA was the primary diagnosis for 89,000 hospital discharges and a listed diagnosis for 113,000 hospital discharges. Clinical trials have demonstrated that improved education in self-management and improved access to care can prevent up to 70 percent of DKA hospitalizations.

Adverse Outcomes of Pregnancy. Each year in the United States, type 1 diabetes complicates approximately 7,000 pregnancies and type 2 diabetes complicates approximately 12,000 pregnancies. Up to 1,700 infants (9%) of mothers with pregnancies complicated by diabetes (in the U.S.) are born with birth defects affecting the brain, spinal cord, heart, kidneys, and skeleton. Clinical trials have demonstrated that with intensive glycemic control before conception and during the first trimester, the incidence of major birth defects may be reduced to 2 percent, the rate that occurs in infants of nondiabetic mothers.

Diabetic Eye Disease. Diabetes is the leading cause of new cases of legal blindness in Americans between twenty and seventy-four years of age. As many as 40,000 Americans become blind each year as a result of diabetes. In type 1 diabetes, most legal blindness is due at least in part to diabetic retinopathy. Timely diagnosis and appropriate laser treatment can prevent up to 90 percent of blindness due to diabetic retinopathy. In type 2 diabetes, cataract, glaucoma, and senile macular degeneration are more frequent causes of blindness.

Diabetic Kidney Disease. Diabetic nephropathy is characterized by hypertension, proteinuria, and progressive renal insufficiency. Diabetes is now the leading cause of end-stage renal disease (kidney failure requiring dialysis or kidney transplant for survival). In 1997, over 33,000 Americans developed end-stage renal disease due to diabetes. Early detection, aggressive blood pressure control, and treatment with angiotensin-converting enzyme inhibitors can reduce the progression of diabetic nephropathy by about 60 percent.

Amputations. Diabetic neuropathy, peripheral vascular disease, and infection predispose people with diabetes to gangrene and amputations. More than half of all nontraumatic lower extremity amputations (LEAs) occur in people with diabetes. In 1994, there were approximately 67,000 diabetes-related hospital discharges with LEA reported as a procedure in the United States. Clinical trials have demonstrated that early detection of insensitive and deformed feet and multidisciplinary foot-care programs can reduce the rate of amputation by more than 50 percent.

Cardiovascular Disease Cardiovascular disease (CVD) is the leading cause of morbidity and

Table 4

Incidence of hospital discharge for cardiovascular disease per 1,000 diabetic population by age and sex, United States, 1994
Age Group
Population	0–44	45–64	65–74	75+	Total
From Centers for Disease Control and Prevention. Diabetes Surveillance, 1997. Atlanta, GA. U.S. Department of Health and Human Services, 1997.
males	34.3	110.6	228.3	264.9	146.3
females	18.3	101.8	191.3	245.8	139.6
Total	26.1	105.8	207.4	253.0	142.7

mortality in people with diabetes. Stroke, heart attack, and peripheral vascular disease are two to four times more common in people with diabetes than in people without diabetes. In 1994, there were 1,144,000 diabetes-related hospital discharges that had CVD listed as the primary discharge diagnosis (see Table 4). Part of the increased incidence of cardiovascular disease in people with diabetes is due to the greater prevalence of cardiovascular risk factors, including hypertension, dyslipidemia, and cigarette smoking. Clinical trials have demonstrated that pharmacologic treatments for hypertension and dyslipidemia are as effective, if not more effective, in people with diabetes compared to people without diabetes.

Costs of Diabetes

Health care costs incurred by people with diabetes include non-diabetes-related and diabetes-related costs. In the United States, in 1992, the direct cost of non-diabetes-related and diabetes-related medical care incurred by people with diabetes was estimated to be $105.2 billion. The direct cost of medical care attributable to diabetes was estimated to be $45.2 billion and the indirect cost of diabetes was estimated to be $46.6 million (see Table 5).

In 1992, per capita health care expenditures for people with diabetes averaged $9,493, compared to $2,604 for people without diabetes. When adjusted for age, per capita health care expenditures for people with diabetes were approximately

Table 5

Costs of diabetes mellitus in the United States, 1992 ($ billion)
Type of Cost	Setting	Attributable to diabetes*	Among People with diabetes**
*From Fox-Ray N, Wills S, Thamer M: Direct and Indirect Costs of Diabetes in the United States in 1992. Alexandria, VA: American Diabetes Association, pp. 1-27, 1993.
**From Rubin RJ, Altman WM, Mendelson DN: Health care expenditures for people with diabetes mellitus, 1992. J Clin Endocrinol Metab 78:809A-809F, 1994.
Direct	Hospital	37.2	65.2
	Nursing home	1.8	—
	Office	1.1	11.0
	Outpatient	2.9	12.5
	Emergency room	0.2	1.3
	Drugs	1.7	9.9
	Home health	0.0	4.0
	Dental	—	1.4
	Total	45.2	105.2
Indirect	Illness	8.5	—
	Disability	11.2	—
	Death	27.0	—
	Total	46.6

$3,800 higher for people with diabetes than for people without diabetes ($6,425 versus $2,604).

The fact that 62 percent of direct health care costs among people with diabetes and 82 percent of costs directly attributable to diabetes are incurred in the hospital setting suggests that the majority of costs are associated with the treatment of the late, chronic complications of diabetes.

Screening for Type 2 Diabetes

One-third of diabetes in the United States is undiagnosed, and one-third to one-half of all diabetes worldwide is undiagnosed. This finding, combined with the fact that glycemic management can prevent or delay the development of complications, and the fact that diabetic patients may already have complications at clinical diagnosis, have lead some to call for public health screening for type 2 diabetes. In general, screening is appropriate in asymptomatic populations when six specific conditions are met (see Table 6).

Table 6

Characteristics of Diseases that Warrant Diabetes Screening
SOURCE: Engelgau, M. M.; Venkat Narayan, K. M.; and Herman, W. H. (2000). "Screening for Type 2 Diabetes." Diabetes Care 23:1563–1580.
The disease represents an important health problem The natural history of the disease is understood The disease has a recognizable preclinical stage during which it may be diagnosed Early treatment confers greater benefit than later treatment Reliable and acceptable tests exist which can detect the preclinical disease The costs of case-finding and treatment are reasonable

Diabetes imposes substantial morbidity and mortality on the population. The natural history of type 2 diabetes is well understood, and with systematic testing, diabetes can be diagnosed in asymptomatic, preclinical, subjects. Unfortunately, although it is clear that intensified management can improve outcomes, no studies have demonstrated the effectiveness or safety of early treatment. Likewise, there is no consensus as to the optimal approach to screening for type 2 diabetes. Ideally, a screening test should be both sensitive and specific. Generally, however, trade-offs must be made between sensitivity and specificity (increasing sensitivity reduces specificity, and increasing specificity reduces sensitivity). In some health systems, the costs of screening and treatment are reasonable, but in others they are simply unaffordable. Finally, although it is recognized that screening must be an ongoing process, no empirical data exist to indicate the optimal screening frequency.

Questionnaires that use self-reported demographic, behavioral, and past medical history to assign a person to a higher or lower risk group; fasting, random, and postprandial urine glucose tests; fasting, random, and postprandial capillary whole blood and capillary plasma glucose tests; fasting, random, and postprandial venous whole blood and plasma glucose tests; and hemoglobin A1c have all been evaluated as screening tests for diabetes. In general, questionnaires perform rather poorly as screening tests for diabetes. Measurement of glycosuria using a cut-off point greater than or equal to a trace value generally has a low sensitivity and a high specificity. Capillary or venous whole blood or plasma glucose determinations have generally performed better than urine glucose testing. With both urine and blood testing, random, postprandial, and glucose-loaded tests perform better than fasting tests. There is little consensus, however, as to optimal cut-points for defining positive tests. Screening with hemoglobin A1c has suffered from lack of standardization of the assay. Even as this problem has been addressed, the test has generally been found to be specific but less sensitive than glucose measurements.

Accordingly, the American Diabetes Association has recommended that clinicians should be vigilant and recognize clinical histories and signs suggestive of diabetes that warrant testing. Generally, screening of high-risk individuals for type 2 diabetes should be performed only as part of ongoing medical care, understanding that the evidence is incomplete and questions remain as to the benefits and risks of early treatment, the optimal screening methods and cut-points, and screening frequency. Community-based screening for diabetes is generally associated with a low yield and poor follow-up, and it probably does not represent a good use of resources.

(SEE ALSO: Cardiovascular Diseases; Glycosylated Hemoglobin; Noncommunicable Disease Control; Nutrition; Screening)

Bibliography

Centers for Disease Control and Prevention (1997). Diabetes Surveillance, 1997. Atlanta, GA: CDC.

DCCT Research Group (1993). "The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus." New England Journal of Medicine 329: 977–986.

Engelgau, M. M.; Venkat Narayan, K. M.; and Herman, W. H. (2000). "Screening for Type 2 Diabetes." Diabetes Care 23:1563–1580.

Fox-Ray, N.; Mills, S.; and Thamer, M. (1993). Direct and Indirect Costs of Diabetes in the United States in 1992. Alexandria, VA: American Diabetes Association.

King, H.; Aubert, R. E.; and Herman, W. H. (1998). "Global Burden of Diabetes, 1995–2025: Prevalence, Numerical Estimates, and Projections." Diabetes Care 21:1414–1431.

Lebovitz, H. E., ed. (1998) Therapy for Diabetes Mellitus and Related Disorders, 3rd edition. Alexandria, VA: American Diabetes Association.

National Diabetes Data Group (1995). Diabetes in America, 2nd edition. Bethesda, MD: National Institute of Health.

Rubin, R. J.; Altman, W. M.; and Mendelson, D. N. (1994). "Health Care Expenditures for People with Diabetes Mellitus, 1992." Journal of Clinical Endocrinolical Metabolism 78:809a–809f.

UK Prospective Diabetes Study (UKPDS) Group (1998). "Intensive Blood-Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes." Lancet 352:857–853. (Published erratum appears in Lancet 354:602.

— WILLIAM H. HERMAN; LIZA L. ILAG

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A disorder of carbohydrate metabolism characterized by an increased blood glucose level (hyperglycaemia) and the presence of glucose in the urine (glycosuria). There are two main types of diabetes mellitus: Type I diabetes (also known as juvenile-onset diabetes and insulin-dependent diabetes) generally has a sudden onset in young people who develop almost total insulin deficiency that usually requires daily insulin injections; Type II diabetes (also known as adult-onset diabetes and non-insulin-dependent diabetes) usually develops gradually in adulthood and is caused by delayed or impaired insulin secretion, impaired insulin action (see insulin resistance), or excessive glucose output by the liver. Exercise is often an important part of the management of diabetes. It can be effective in modifying the course of the disease, helping to reduce the risk of vascular complications (e.g. coronary artery disease). Regular aerobic exercise might also reduce the risk of developing Type II diabetes and it improves the control of food glucose levels in those who already have the disease. However, it is important that the diabetic, coach, and friends are well acquainted with potential problems during exercise, such as hypoglycaemia. A glucose drink or some other simple and quick source of glucose should be available if needed to prevent insulin shock. Physical activity reduces the concentration of insulin in the blood, and acute bouts of exercise increases the sensitivity of target cells to insulin, reducing the dosages required by a diabetic. Diabetics often suffer complications such as peripheral neuropathy which can reduce sensation in the feet and peripheral vascular disease, which may impair blood circulation in the feet. They therefore need to pay particular attention to their feet, taking care to select proper footwear, especially if they perform weight-bearing exercises (e.g. road running). The American Academy of Pediatrics, Committee on Sports Medicine states that diabetics can participate in all sports with proper attention to blood glucose concentration, hydration, and insulin therapy. The Committee advises that blood glucose concentration should be monitored every 30 min during continuous exercise and 15 min after completion of exercise.

Diabetes, Heart Disease, and Stroke Many people with diabetes are not aware that they are at particularly high risk for heart disease and stroke, which can result from the poor blood flow that is a symptom of diabetes. In addition, people with type 2 diabetes have higher rates of hypertension and obesity, which are additional risk factors. Diabetics are two to four times more likely to have a heart attack than nondiabetics, and at least 65 percent of people with diabetes die from heart attack or stroke. While deaths from heart disease have been declining overall, deaths from heart disease among women with diabetes have increased, and deaths from heart disease among men with diabetes have not declined nearly as rapidly as they have among the general male population. The National Diabetes Education Program has launched a campaign to bring the problem to public attention. Patients are advised to work with medical personnel to control their glucose level, blood pressure, and cholesterol level and, of course, to avoid smoking.

Diabetes mellitus is a common metabolic disorder resulting from defects in insulin action, insulin production, or both. Insulin, a hormone secreted by the pancreas, helps the body use and store glucose produced during the digestion of food. Characterized by hyperglycemia, symptoms of diabetes include frequent urination, increased thirst, dehydration, weight loss, blurred vision, fatigue, and, occasionally, coma. Uncontrolled hyperglycemia over time damages the eyes, nerves, blood vessels, kidneys, and heart, causing organ dysfunction and failure. A number of risk factors are attributed to the incidence of diabetes, including family history, age, ethnicity, and social group characteristics, as well as behavioral, lifestyle, psychological, and clinical factors.

The World Health Organization estimates that 150 million people had diabetes worldwide in 2002. This number is projected to double by the year 2025. Much of this increase will occur in developing countries and will be due to population growth, aging, unhealthful diets, obesity, and sedentary lifestyles. In the United States, diabetes is the sixth leading cause of death. While 6.2 percent of the population has diabetes, an estimated 5.9 million people are unaware they have the disease. In addition, about 19 percent of all deaths in the United States for those age twenty-five and older are due to diabetes-related complications.

The prevalence of diabetes varies by age, gender, race, and ethnicity. In the United States, about 0.19 percent of the population less than twenty years of age (151,000 people) have diabetes, versus 8.6 percent of the population twenty years of age and older. In addition, adults sixty-five and older account for 40 percent of those with diabetes, despite composing only 12 percent of the population. Considerable variations also exist in the prevalence of diabetes among various racial and ethnic groups. For example, 7.8 percent of non-Hispanic whites, 13 percent of non-Hispanic blacks, 10.2 percent of Hispanic/Latino Americans, and 15.1 percent of American Indians and Alaskan Natives have diabetes. Among Asian Americans and Pacific Islanders, the rate of diabetes varies substantially and is estimated at 15 to 20 percent. The prevalence of diabetes is comparable for males and females—8.3 and 8.9 percent respectively. Nevertheless, the disease is more devastating and more difficult to control among women, especially African-American and non-Hispanic white women. In fact, the risk for death is greater among young people (3.6 times greater for people from 25 to 44 years of age) and women (2.7 times greater for women ages 45 to 64 than men of the same age).

Types of Diabetes
Diabetes mellitus is classified into four categories: type 1, type 2, gestational diabetes, and other. In type 1 diabetes, specialized cells in the pancreas are destroyed, leading to a deficiency in insulin production. Type 1 diabetes frequently develops over the course of a few days or weeks. Over 95 percent of people with type 1 diabetes are diagnosed before the age of twenty-five. Estimates show 5.3 million people worldwide live with type 1 diabetes. Although the diagnosis of type 1 diabetes occurs equally among men and women, an increased prevalence exists in the white population. Type 1 diabetes in Asian children is relatively rare.

Family history, diet, and environmental factors are risk factors for type 1 diabetes. Studies have found an increased risk in children whose parents have type 1 diabetes, and this risk increases with maternal age. Environmental factors such as viral infections, toxins, and exposure to cow's milk are being contested as causing or modifying the development of type 1 diabetes.

Type 2 diabetes is characterized by insulin resistance and/or decreased insulin secretion. It is the most common form of diabetes mellitus, accounting for 90 to 95 percent of all diabetes cases worldwide. Risk factors for type 2 diabetes include family history, increasing age, obesity, physical inactivity, ethnicity, and a history of gestational diabetes. Although type 2 diabetes is frequently diagnosed in adult populations, an increasing number of children and adolescents are currently being diagnosed. Type 2 diabetes is also more common in blacks, Hispanics, Native Americans, and women, especially women with a history of gestational diabetes.

Genetics and environmental factors are the main contributors to type 2 diabetes. Physical inactivity and adoption of a Western lifestyle (particularly choosing foods with more animal protein, animal fats, and processed carbohydrates), especially in indigenous people in North American and within ethnic groups and migrants, have contributed to weight gain and obesity. In fact, obesity levels increased by 74 percent between 1991 and 2003. Increased body fat and abdominal obesity are associated with insulin resistance, a precursor to diabetes. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are two prediabetic conditions associated with insulin resistance. In these conditions, the blood glucose concentration is above the normal range, but below levels required to diagnose diabetes. Subjects with IGT and/or IFG are at substantially higher risk of developing diabetes and cardiovascular disease than those with normal glucose tolerance. The conversion of individuals with IGT to type 2 diabetes varies with ethnicity, anthropometric measures related to obesity, fasting blood glucose (a measurement of blood glucose values after not eating for 12 to 14 hours), and the two-hour post-glucose load level (a measurement of blood glucose taken exactly two hours after eating). In addition to IGT and IFG, higher than normal levels of fasting insulin, called hyperinsulinemia, are associated with an increased risk of developing type 2 diabetes. Insulin levels are higher in African Americans than in whites, particularly African-American women, indicating their greater predisposition for developing type 2 diabetes.

The complexity of inheritance and interaction with the environment makes identification of genes involved with type 2 diabetes difficult. Only a small percentage (2–5%) of diabetes cases can be explained by single gene defects and are usually atypical cases. However, a "thrifty gene," although not yet identified, is considered predictive of weight gain and the development of type 2 diabetes. Thrifty-gene theory suggests that indigenous people who experienced alternating periods of feast and famine gradually developed a way to store fat more efficiently during periods of plenty to better survive famines. Regardless of the thrifty gene, the contribution of genetic mutations in the development of type 2 diabetes has not been established, due to the number of genes that may be involved.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. This definition applies regardless of whether insulin or diet modification is used for treatment, and whether or not the condition persists after pregnancy. GDM affects up to 14 percent of the pregnant population—approximately 135,000 women per year in United States. GDM complicates about 4 percent of all pregnancies in the U.S. Women at greatest risk for developing GDM are obese, older than twenty-five years of age, have a previous history of abnormal glucose control, have first-degree relatives with diabetes, or are members of ethnic groups with a high prevalence of diabetes. Infants of a woman with GDM are at a higher risk of developing obesity, impaired glucose tolerance, or diabetes at an early age. After a pregnancy with GDM, the mother has an increased risk of developing type 2 diabetes.

Other forms of diabetes are associated with genetic defects in the specialized cells of the pancreas, drug or chemical use, infections, or other diseases. The most notable of the genetically linked diabetes is maturity onset diabetes of the young (MODY). Characterized by the onset of hyperglycemia before the age of twenty-five, insulin secretion is impaired while minimal or no defects exist in insulin action. Drugs, infections, and diseases cause diabetes by damaging the pancreas and/or impairing insulin action or secretion.

Diabetes Complications
People with diabetes are at increased risk for serious long-term complications. Hyperglycemia, as measured by fasting plasma glucose concentration or glycosylated hemoglobin (HbA1c), causes structural and functional changes in the retina, nerves, kidneys, and blood vessels. This damage can lead to blindness, numbness, reduced circulation, amputations, kidney disease, and cardiovascular disease. Type 1 diabetes is more likely to lead to kidney failure. About 40 percent of people with type 1 diabetes develop severe kidney disease and kidney failure by the age of fifty. Nevertheless, between 1993 and 1997, more than 100,000 people in the United States were treated for kidney failure caused by type 2 diabetes.

African Americans experience higher rates of diabetes-related complications such as eye disease, kidney failure, and amputations. They also experience greater disability from these complications. The frequency of diabetic retinopathy (disease of the small blood vessels in the retina causing deterioration of eyesight) is 40 to 50 percent higher in African Americans than in white Americans. In addition, the rate of diabetic retinopathy among Mexican Americans is more than twice that of non-Hispanic white Americans. Furthermore, African Americans with diabetes are much more likely to undergo a lower-extremity amputation than white or Hispanic Americans with diabetes. Little is known about these complications in Asian and Pacific Islander-Americans.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia state (HHS) are serious diabetic emergencies and the most frequent cause of mortality. Both DKA and HHS result from an insulin deficiency and an increase in counter-regulatory hormones (a.k.a. hyperglycemia). Hyperglycemia leads to glycosuria (glucose in the urine), increased urine output, and dehydration. Because the glucose is excreted in the urine, the body becomes starved for energy. At this point, the body either continues to excrete glucose in the urine making the hyperglycemia worse (HHS), or the body begins to break down triglycerides causing the release of ketones (by-products of fat breakdown) into the urine and bloodstream (DKA). The mortality rate of patients with DKA is less than 5 percent while the mortality rate of HHS patients is about 15 percent. Infection (urinary tract infections and pneumonia account for 30 to 50 percent of cases), omission of insulin, and increased amounts of counter-regulatory hormones contribute to DKA and HHS. Type 1 and type 2 diabetic patients may experience DKA and HHS. However, DKA is more common in type 1 diabetic patients, while HHS is more common in type 2 diabetic patients. Treatment of DKA and HHS involves correction of dehydration, hyperglycemia, ketoacidosis, and electrolyte deficits and imbalances.

Treatment for Diabetes
Treatment for diabetes involves following a regimen of diet, exercise, self-monitoring of blood glucose, and taking medication or insulin injections. Although type 1 diabetes is primarily managed with daily insulin injections, type 2 diabetes can be controlled with diet and exercise. However, when diet and exercise fail, medication is added to stimulate the production of insulin, reduce insulin resistance, decrease the liver's output of glucose, or slow absorption of carbohydrate from the gastrointestinal tract. When medication fails, insulin is required.

Following the diagnosis of diabetes, a diabetic patient undergoes medical nutrition therapy. In other words, a registered dietician performs a nutritional assessment to evaluate the diabetic patient's food intake, metabolic status, lifestyle, and readiness to make changes, along with providing dietary instruction and goal setting. The assessment is individualized and takes into account cultural, lifestyle, and financial considerations. The goals of medical nutrition therapy are to attain appropriate blood glucose, lipid, cholesterol, and triglyceride levels, which are critical to preventing the chronic complications associated with diabetes. For meal planning, the diabetic exchange system provides a quick method for estimating and maintaining the proper balance of carbohydrates, fats, proteins, and calories. In the exchange system, foods are categorized into groups, with each group having food with similar amounts of carbohydrate, protein, fat, and calories. Based on the individual's diabetes treatment plan and goals, any food on the list can be exchanged with another food within the same group.

Exercise and blood glucose monitoring are also critical components of a diabetic patient's self-management. Exercise improves blood glucose control, increases sensitivity to insulin, reduces cardiovascular risk factors, contributes to weight loss, and improves well-being. Exercise further contributes to a reduction in the risk factors for diabetes-related complications. Daily self-monitoring of blood glucose levels allows diabetic patients to evaluate and make adjustments in diet, exercise, and medications. Self-monitoring also assists in preventing hypoglycemic episodes.

Diabetes mellitus is a chronic and debilitating disease. Attributed to genetics, physical inactivity, obesity, ethnicity, and a number of environmental factors, diabetes requires lifestyle changes and medication adherence in order to control blood glucose levels. Due to the damage caused by hyperglycemia, diabetic patients also experience a number of complications related to the disease. With good self-management practices, however, individuals with diabetes can live a long and productive life.

See also Carbohydrates; Exchange system; Glycemic index; Hyperglycemia; Hypoglycemia; Insulin.

Bibliography
American Diabetes Association (2003) "Gestational Diabetes Mellitus." Diabetes Care 26(1):S103–S105.
American Diabetes Association (2003) "Hyperglycemic Crises in Patients with Diabetes Mellitus." Diabetes Care 26(1):S109–S117.
American Diabetes Association (2003) "Physical Activity/Exercise and Diabetes Mellitus." Diabetes Care 26(1):S73–77.
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Mandrup-Paulson, Thomas (1998). "Recent Advances: Diabetes." British Medical Journal 316(18):1221–1225.
Mokdad, Ali H.; Ford, Earl S.; Bowman, Barbara A.; Dietz, William, H.; Vinicor, Frank; Bales, Virginia, S.; and Marks, James S. (2003). "Prevalence of Obesity, Diabetes, and Obesity-Related Health Risk Factors, 2001." Journal of the American Medical Association 289(1):76–79.
Jovanovic, Lois, and Pettitt, David J. (2001). "Gestational Diabetes Mellitus." Journal of the American Medical Association 283(20):2516–2518.
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Yki-Jarvinen, Hannele (1998). "Toxicity of Hyperglycemia in Type 2 Diabetes." Diabetes/Metabolism Reviews 14:S45–S50.

Internet Resources
American Diabetes Association. "Basic Diabetes Information." Available from http://www.diabetes.org
Centers for Disease Control and Prevention. "Diabetes Public Health Resource." Available from http://www.cdc.gov/diabetes
National Diabetes Information Clearinghouse (NDIC). "Diabetes." Available from http://diabetes.niddk.nih.gov
World Health Organization. "Fact Sheets: Diabetes Mellitus." Available from http://www.who.int

KEY TERMS Cataract—A condition where the lens of the eye becomes cloudy. Diabetic peripheral neuropathy—A condition where the sensitivity of nerves to pain, temperature, and pressure is dulled, particularly in the legs and feet. Diabetic retinopathy—A condition where the tiny blood vessels to the retina, the tissues that sense light at the back of the eye, are damaged, leading to blurred vision, sudden blindness, or black spots, lines, or flashing lights in the field of vision. Glaucoma—A condition where pressure within the eye causes damage to the optic nerve, which sends visual images to the brain. Hyperglycemia—A condition where there is too much glucose or sugar in the blood. Hypoglycemia—A condition where there is too little glucose or sugar in the blood. Insulin—A hormone or chemical produced by the pancreas, insulin is needed by cells of the body in order to use glucose (sugar), the body’s main source of energy. Ketoacidosis—A condition due to starvation or uncontrolled Type I diabetes. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins. Symptoms include abdominal pain, vomiting, rapid breathing, extreme tiredness, and drowsiness. Kidney dialysis—A process where blood is filtered through a dialysis machine to remove waste products that would normally be removed by the kidneys. The filtered blood is then circulated back into the patient. This process also is called renal dialysis. Pancreas—A gland located behind the stomach that produces insulin.

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What is Diabetes Mellitus?

Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or cells stop responding to the insulin that is produced, so that glucose in the blood cannot be absorbed into the cells of the body. Symptoms include frequent urination, lethargy, excessive thirst, and hunger. The treatment includes changes in diet, oral medications, and in some cases, daily injections of insulin.

Description of Diabetes Mellitus

Diabetes mellitus is a chronic disease that causes serious health complications including renal (kidney) failure, heart disease, stroke, and blindness. Approximately 17 million Americans have diabetes. Unfortunately, as many as one-half are unaware they have it.

Background
Every cell in the human body needs energy in order to function. The body’s primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for any cells that need it. Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin bonds to a receptor site on the outside of cell and acts like a key to open a doorway into the cell through which glucose can enter. Some of the glucose can be converted to concentrated energy sources like glycogen or fatty acids and saved for later use. When there is not enough insulin produced or when the doorway no longer recognizes the insulin key, glucose stays in the blood rather entering the cells.

The body will attempt to dilute the high level of glucose in the blood, a condition called hyperglyce-mia, by drawing water out of the cells and into the bloodstream in an effort to dilute the sugar and excrete it in the urine. It is not unusual for people with undiag-nosed diabetes to be constantly thirsty, drink large quantities of water, and urinate frequently as their bodies try to get rid of the extra glucose. This creates high levels of glucose in the urine.

At the same time that the body is trying to get rid of glucose from the blood, the cells are starving for glucose and sending signals to the body to eat more food, thus making patients extremely hungry. To provide energy for the starving cells, the body also tries to convert fats and proteins to glucose. The breakdown of fats and proteins for energy causes acid compounds called ketones to form in the blood. Ketones also will be excreted in the urine. As ketones build up in the blood, a condition called ketoa-cidosis can occur. This condition can be life threatening if left untreated, leading to coma and death.

Types of diabetes mellitus
Type I diabetes, sometimes called juvenile diabetes, begins most commonly in childhood or adolescence. In this form of diabetes, the body produces.

little or no insulin. It is characterized by a sudden onset and occurs more frequently in populations descended from Northern European countries (Finland, Scotland, Scandinavia) than in those from Southern European countries, the Middle East, or Asia. In the United States, approximately three people in 1,000 develop Type I diabetes. This form also is called insulin-dependent diabetes because people who develop this type need to have daily injections of insulin.

Brittle diabetics are a subgroup of Type I where patients have frequent and rapid swings of blood sugar levels between hyperglycemia (a condition where there is too much glucose or sugar in the blood) and hypoglycemia (a condition where there are abnormally low levels of glucose or sugar in the blood). These patients may require several injections of different types of insulin during the day to keep the blood sugar level within a fairly normal range.

The more common form of diabetes, Type II, occurs in approximately 3–5% of Americans under 50 years of age, and increases to 10–15% in those over 50. More than 90% of the diabetics in the United States are Type II diabetics. Sometimes called age-onset or adult-onset diabetes, this form of diabetes occurs most often in people who are overweight and who do not exercise. It is also more common in people of Native American, Hispanic, and African-American descent. People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures also are more likely to develop Type II diabetes than those who remain in their original countries.

Type II is considered a milder form of diabetes because of its slow onset (sometimes developing over the course of several years) and because it usually can be controlled with diet and oral medication. The consequences of uncontrolled and untreated Type II diabetes, however, are the just as serious as those for Type I. This form is also called noninsulin-dependent diabetes, a term that is somewhat misleading. Many people with Type II diabetes can control the condition with diet and oral medications, however, insulin injections are sometimes necessary if treatment with diet and oral medication is not working.

Another form of diabetes called gestational diabetes can develop during pregnancy and generally resolves after the baby is delivered. This diabetic condition develops during the second or third trimester of pregnancy in about 2% of pregnancies. In 2004, incidence of gestational diabetes were reported to have increased 35% in 10 years. Children of women with gestational diabetes are more likely to be born prematurely, have hypoglycemia, or have severe jaundice at birth. The condition usually is treated by diet, however, insulin injections may be required. These women who have diabetes during pregnancy are at higher risk for developing Type II diabetes within 5–10 years.

Diabetes also can develop as a result of pancreatic disease, alcoholism, malnutrition, or other severe illnesses that stress the body.

Target blood glucose levels for people with diabetes

Before meals	90 to 130
1 to 2 hours after the start of a meal	less than 180

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services.

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(deye-uh-bee-teez, deye-uh-bee-tuhs mel-uh-tuhs)

A chronic disease in which carbohydrates cannot be metabolized properly (see metabolism) because the pancreas fails to secrete an adequate amount of insulin. Without enough insulin, carbohydrate metabolism is upset, and levels of sugar in the blood rise.

an alternative name for type 2 diabetes mellitus.

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A broadly applied term used to denote a complex group of syndromes that have in common a disturbance in the oxidation and utilization of glucose, which is secondary to a malfunction of the beta cells of the pancreas, whose function is the production and release of insulin. Because insulin is involved in the metabolism of carbohydrates, proteins and fats, diabetes is not limited to a disturbance of glucose homeostasis alone.
Diabetes mellitus has been recorded in all species but is most commonly seen in middle-aged to older, obese, female dogs. A familial predisposition has been suggested. It is possible to identify two types of diabetes, corresponding to the disease in humans, depending on the response to an intravenous glucose tolerance test. Type I is insulin-dependent and comparable to the juvenile onset form of the disease in children in which there is an absolute deficiency of insulin—there is a very low initial blood insulin level and a low response to the injected glucose. This form is seen in a number of dog breeds, particularly the Keeshond, Doberman pinscher, German shepherd dog, Poodle, Golden retriever and Labrador retriever.
Type II is non-insulin-dependent, similar to the adult onset diabetes in humans due to pancreatic damage—there is a high or normal initial blood insulin level and no increase in insulin levels as a result of the glucose load. It is the form seen most often in cats.

• brittle d. m. — diabetes mellitus that is difficult to control, characterized by unexplained oscillation between hypoglycemia and diabetic ketoacidosis.
• gestational d. m. — diabetes mellitus in which onset or recognition of impaired glucose tolerance occurs during pregnancy.
• hyperosmolar d. m. — a syndrome of marked hyperglycemia and hyperosmolarity with central nervous signs, resembling diabetic coma.
• insulin-dependent d. m. (IDDM) — due to deficient secretion of insulin by the beta cells of the pancreas. See diabetes mellitus type I (above).
• juvenile d. m. — develops in the young; see diabetes mellitus type I (above).
• non-insulin-dependent d. m. (NIDDM) — the secretion of insulin is unimpaired but the response of tissue receptors is diminished. See diabetes mellitus type II (above).
• secondary d. m. — hyperglycemia may occur in association with pancreatitis, hyperadrenocorticism, acromegaly, and treatment with glucocorticoids or progesterone.
• steroid d. m. — altered carbohydrate tolerance is induced by glucocorticoids and progestogens. Hyperglycemia and diabetes mellitus can be associated with the administration of such drugs or hyperadrenocorticism.

n

A metabolic disorder caused primarily by a defect in the production of insulin by the islet cells of the pancreas resulting in an inability to use carbohydrates. Characterized by hyperglycemia, glycosuria, polyuria, hyperlipemia (caused by imperfect catabolism of fats), acidosis, ketonuria, and a lowered resistance to infection. Periodontal manifestations may include recurrent and multiple periodontal abscesses, osteoporotic changes in alveolar bone, fungating masses of granulation tissue protruding from periodontal pockets, a lowered resistance to infection, and delay in healing after periodontal therapy.

For a list of words related to diabetes mellitus, see:

• Diseases and Infestations - diabetes mellitus: common deficiency, possibly inherited, of the pancreatic hormone insulin, causing disorder in carbohydrate metabolism and inability to properly utilize sugars; diabetes

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