Diabetes mellitus

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: http://www.diabetes.org.

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

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

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

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

WEB SITES

"2004 Clinical Practice Recommendations." Diabetes Care , January, 2004. Available online at http://care.diabetesjournals.org/content/vol27/suppl_1/ (accessed December 26, 2004).

Ford-Martin, Paula. "About Diabetes" Available online at http://diabetes.about.com (accessed December 26, 2004).

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

Paula Ford-Martin Altha Roberts Edgren Teresa G. Odle