Diabetes Mellitus (DM) in Children and Adolescents

Prediabetes is a condition in which blood glucose levels are too high to be considered normal but not high enough to be considered diabetes. Among children, prediabetes is more common among obese adolescents. It is temporary in over half of adolescents, but the remainder develop diabetes, especially those who continue to gain weight.

Type 1 diabetes occurs when the pancreas produces little to no insulin. Type 1 diabetes is the most common type among children, causing about two thirds of all cases of diabetes. It is one of the most common chronic childhood diseases. By age 18, 1 in 350 children has developed type 1 diabetes. The number of affected children has recently been increasing, particularly in children under age 5.

Type 1 diabetes can develop at any time during childhood, even during infancy, but it usually begins between ages 4 years and 6 years or between ages 10 years and 14 years.

In type 1 diabetes, the pancreas does not produce enough insulin because the immune system attacks and destroys the cells in the pancreas that make insulin (islet cells). Such an attack may be triggered by environmental factors in people who have inherited certain genes that make them susceptible to developing diabetes. These genes are more common among certain ethnic groups (such as Scandinavians and Sardinians). Close relatives of a person with type 1 diabetes are at increased risk of developing diabetes. Brothers and sisters have about a 4 to 8% risk, and identical twins have a much greater 30 to 50% risk. The risk of diabetes for a child who has a parent with type 1 diabetes is about 10% if the father is affected and is about 4% if the mother is affected.

Children who have type 1 diabetes are at higher risk of some other disorders in which the body's immune system attacks itself (autoimmune disorders), particularly certain types of thyroid disease, and celiac disease.

Type 2 diabetes occurs because the cells in the body do not respond adequately to insulin (called insulin resistance). Unlike in type 1 diabetes, the pancreas can still make insulin but cannot make enough insulin to overcome insulin resistance. This deficiency is often referred to as a relative insulin deficiency as opposed to the absolute deficiency seen in type 1 diabetes.

Among children, type 2 diabetes occurs mainly in adolescents but is becoming increasingly common among overweight or obese younger children. Up until the 1990s, more than 95% of children who developed diabetes had type 1 diabetes, but now, mainly because of the increase in the number of children who are overweight or obese, about one third of children newly diagnosed with diabetes have type 2 diabetes. Type 2 diabetes typically develops after puberty has begun. Although many children develop type 2 diabetes between 10 years and 14 years of age, the highest rate occurs during late adolescence, between 15 years and 19 years of age (see Obesity in Adolescents). Compared to children with type 1 diabetes, children with type 2 diabetes are much more likely to have a first-degree relative (parent, sibling, aunt, uncle, or grandparent) with type 2 diabetes.

The increase in childhood type 2 diabetes has been particularly prominent among people who are Native American, Black, Hispanic, Asian American, and Pacific Islander.

Other children at higher risk of developing type 2 diabetes include those who

• Are overweight (weigh more than 85% of children of similar age, sex, and height), particularly those who are obese (weigh more than 95% of children of similar age, sex, and height)

• Have a parent, sibling, aunt, uncle, or grandparent who has type 2 diabetes (60 to 90%)

• Have high blood pressure, high blood levels of lipids (fats), obstructive sleep apnea, dark and thick skinfolds on the nape of the neck (acanthosis nigricans), fatty liver, polycystic ovary syndrome (PCOS), or a small-for-gestational-age birth weight

• Have a mother who had diabetes while pregnant (gestational diabetes) or who has a history of diabetes

• Are not physically active

Symptoms develop quickly in type 1 diabetes, usually over several days to weeks, and tend to appear in a typical pattern. High blood glucose levels cause the child to urinate excessively. Children may wet the bed or become unable to control their bladder during the day. Children who are not toilet-trained may have an increase in wet or heavy diapers. This fluid loss causes an increase in thirst and the consumption of fluids. About half of children lose weight and have impaired growth. Some children become dehydrated, resulting in weakness, fatigue, and a rapid pulse. Children may also have nausea and vomiting due to ketones (by-products of the breakdown of fat) in their blood. Vision may become blurred. If the symptoms are not recognized as being caused by diabetes and treated, children may develop diabetic ketoacidosis.

Many children do not have any symptoms or have only mild symptoms, and doctors diagnose type 2 diabetes only when blood or urine tests are done for other reasons (such as during a physical before playing sports or going to camp). Symptoms in children with type 2 diabetes are milder than those in type 1 diabetes and develop more slowly. Parents may notice an increase in the child’s thirst and urination or only vague symptoms, such as fatigue. Children with type 2 diabetes are less likely to develop ketoacidosis or severe dehydration than those with type 1 diabetes.

Diabetic ketoacidosis is present at the time of diagnosis in about one third of children with type 1 diabetes. Diabetic ketoacidosis is also common among children with known type 1 diabetes. It develops in about 1 to 10% of children with type 1 diabetes each year, usually because these children have not taken their insulin or are having problems with insulin delivery (for example, problems with their ). Diabetic ketoacidosis can also occur if children do not receive enough insulininsulin, cells cannot use the glucose that is in the blood. Cells switch to a back-up mechanism to obtain energy and break down fat, producing compounds called ketones as by-products.

Ketones make the blood too acidic (ketoacidosis), causing nausea, vomiting, fatigue, and abdominal pain. The ketones make the child’s breath smell like nail polish remover. Breathing becomes deep and rapid as the body attempts to correct the blood’s acidity ( see Overview of Acid-Base Balance). Some children develop a headache and may become confused or less alert. These symptoms may be caused by accumulation of fluid in the brain (cerebral edema). Diabetic ketoacidosis, when untreated, can progress to coma and death. Children with diabetic ketoacidosis are also dehydrated and often have other chemical imbalances in the blood, such as abnormal levels of potassium and sodium.

Mental health problems ( see Support) are very common among children with diabetes. Up to half of children develop depression, anxiety, or other psychologic problems ( see Overview of Mental Health Disorders Children and Adolescents). Because insulin can cause weight gain, eating disorders are a serious problem in adolescents, who sometimes skip their insulin doses to try to control their weight. Mental health problems can affect children's ability to follow their meal plan and drug regimens, which means their blood glucose is poorly controlled.

Diabetes eventually causes narrowing of small and large blood vessels. The narrowing can damage many different organs. Although the blood vessel narrowing starts to develop within a few years after diabetes begins, the organ damage usually does not become apparent until years later and is rarely present during childhood.

Damage to small blood vessels most often affects the eyes, kidneys, and the nerves. Damage to the blood vessels of the eyes can cause loss of vision (diabetic retinopathy). Damage to the kidneys (called diabetic nephropathy) can result in kidney failure. Damage to the nerves (called diabetic neuropathy) can result in numbness, tingling, or burning pain in the arms and legs. These problems are more common among children who have type 2 diabetes than type 1 diabetes. These problems also may be present at the time of diagnosis or earlier in children who have type 2 diabetes.

Damage to large blood vessels most often involves the arteries to the heart and the brain. Narrowing of arteries to the heart can cause heart attack. Narrowing of arteries to the brain can cause stroke. Heart attack and stroke do not commonly occur during childhood.

Doctors suspect diabetes when children have typical symptoms or when a urine test done during a routine physical examination reveals glucose. The diagnosis is confirmed by measurement of the blood glucose level. Blood glucose levels can be measured in the morning before children eat (called the fasting glucose level) or without regard to meals (called the random glucose level). Children are considered to have diabetes if they have both typical symptoms of diabetes and a high blood glucose level. If the fasting glucose level is 126 milligrams per deciliter (mg/dL—7.0 mmol/L) or higher on 2 different occasions, children have diabetes. If the random glucose level is 200 mg/dL (11.1 mmol/L) or higher, children probably have diabetes and should have their fasting glucose level tested to confirm.

Doctors also measure the level of a protein in the blood called hemoglobin A1c (HbA1c). Hemoglobin is the red, oxygen-carrying substance within red blood cells. When blood is exposed to high blood glucose levels over a period of time, glucose attaches to the hemoglobin and forms HbA1c. Because HbA1c takes a relatively long time to form and to break down, levels change only over weeks to months rather than from minute to minute like blood glucose levels do. HbA1c levels thus reflect blood glucose levels over a 2- to 3-month period of time. People whose HbA1c level is 6.5% or higher are considered to have diabetes. HbA1c levels are more helpful in the diagnosis of type 2 diabetes in children who do not have typical symptoms.

Another kind of blood test called an oral glucose tolerance test may be done in children who have no symptoms or whose symptoms are mild or not typical. In this test, children fast, have a blood sample taken to determine the fasting glucose level, and then drink a special solution containing a large amount of glucose. Doctors then measure blood glucose levels 2 hours later. If the level is 200 mg/dL (11.1 mmol/L) or higher, children are considered to have diabetes. This test is similar to the test that pregnant women have to look for gestational diabetes.

To help distinguish type 1 diabetes from type 2, doctors do blood tests that detect antibodies to various proteins produced by the insulin-producing cells in the pancreas. Such antibodies are usually present in children with type 1 diabetes and are rarely present in children with type 2 diabetes.

Children who are diagnosed with type 1 diabetes usually have other blood tests to look for autoimmune disorders such as celiac disease and thyroid disease. These tests are done at diagnosis and every 1 to 2 years thereafter. Doctors sometimes do tests to look for other problems such as a disorder of the adrenal glands (Addison disease), joint and muscle disorders (such as rheumatoid arthritis), and additional digestive tract disorders (such as inflammatory bowel disease).

Children who are diagnosed with type 2 diabetes have blood tests to determine how their liver and kidneys are functioning and urine tests. At diagnosis, children who have type 2 diabetes are also tested for other problems, such as high blood pressure, high blood levels of lipids (fats), and fatty liver, because these problems are common among children with type 2 diabetes. Other tests are done depending on symptoms. For example, children with daytime sleepiness who snore are tested for obstructive sleep apnea and adolescent girls who are hairy and have acne or menstrual irregularities are tested for polycystic ovary syndrome.

Children with either type of diabetes need to

• Make healthy food choices

• Lose weight if overweight

• Exercise regularly

General nutritional management and education are particularly important for all children with diabetes. Dietary recommendations for children with diabetes are based on healthy eating recommendations for all children and aim to maintain ideal body weight and optimal growth and to prevent short-term and long-term complications of diabetes.

All children should eat regularly and not skip meals. Although most dietary regimens allow some flexibility in carbohydrate intake and meal times, having meals and scheduled snacks at about the same time each day and that contain similar amounts of carbohydrates is important for optimal glucose control. Because carbohydrates in food are turned into glucose by the body, variations in carbohydrate intake cause variations in blood glucose levels.

Choosing healthy foods can help control blood glucose and protect heart health. Children should focus on eating fruits and vegetables, whole grains, and high-fiber foods (for example, foods that have at least 3 grams fiber or more per serving). Food should not contain many highly processed (refined) carbohydrates, particularly candy, baked goods (such as cookies, donuts, and pastries), and sugary drinks. Children should have no more than 4 to 8 ounces of 100% fruit juice per day. They should avoid regular soda, sweetened iced tea, lemonade, fruit punch, and sports drinks altogether. Children also should avoid foods with saturated fats, such as baked goods, snack foods (such as potato chips and corn tortilla chips), deep-fried foods (such as french fries), and fast food. Some of these foods may still contain trans fats, common ingredients in certain commercial foods, which are being removed because they have been shown to be associated with an increased risk of heart disease.

In type 1 diabetes, parents and older children are taught how to gauge the carbohydrate content of food and to develop a meal plan. In most children with type 1 diabetes, food intake is not rigidly specified and is based on the child's usual eating patterns and insulin doses are matched to actual carbohydrate intake. Infants and preschool-aged children present a particular challenge to parents because they do not eat consistent amounts of food and because they may develop hypoglycemia but may not be able to communicate symptoms of hypoglycemia to their parents.

In type 2 diabetes, lifestyle modifications focus on weight in the majority of children. Steps to improve food choices and manage food intake include eliminating sugary drinks, controlling portion size, switching to low-fat foods, and increasing fiber by eating more fruits and vegetables.

Regular exercise is important because it improves glucose control and makes it easier to lose weight. Because vigorous exercise can cause a significant drop in blood glucose, some children with type 1 diabetes may need to consume some extra carbohydrates before and/or during a workout.

Children with diabetic ketoacidosis (DKA) are usually treated in an intensive care unit. They often require fluids given by vein (intravenously) to correct dehydration. They often also need intravenous potassium solutions to correct low potassium levels. Children often require intravenous insulin during DKA.

To prevent the development of DKA and minimize the need for hospitalization, children and families should use ketone test strips to check for ketones in blood or urine. Blood testing may be preferred in younger children and in others in whom it is difficult to obtain a urine sample, those who have frequent episodes of DKA, and insulin pump users. Ketone testing should be done whenever children become ill (regardless of the blood glucose level) or when the blood glucose is high. High ketone levels may indicate DKA, especially if children also have abdominal pain, vomiting, drowsiness, or rapid breathing.

When type 1 diabetes is first diagnosed, children are usually hospitalized. Children with type 1 diabetes are given fluids (to treat dehydration) and insulin. They always require insulin because nothing else is effective. Children who do not have DKA at diagnosis typically receive two or more daily injections of insulin. Insulin treatment is usually begun in the hospital so that blood glucose levels can be tested often and doctors can change insulin dosage in response. Less commonly, treatment is started at a regular doctor visit.

Once children are released from the hospital, they must take insulin regularly. Doctors work with children and their family to determine which insulin regimen is best.

There are several types of insulin regimens:

• Multiple daily injections (MDI) regimen using a basal-bolus regimen

• Premixed insulin regimen (less common)

Most children who have type 1 diabetes should be treated with MDI regimens or with insulin pump therapy.

With MDI regimens,insulin (basal dose) every day and then separate supplemental injections (bolus doses) of a short-acting insulin immediately before meals. Each bolus dose can be different depending on how much food the child is going to eat or what the blood glucose level is at that time.

An advantage of the basal-bolus regimen is that it allows for flexibility as to when meals are eaten and how much is eaten.

Fixed forms of MDI regimens are less commonly used. If a basal-bolus regimen is not an option (for example, if adequate supervision is not available, such as when an adult is not available to give injections at school or daycare), fixed forms of MDI regimens can be an option. In these regimens, children typically receive a specific (fixed) amount of shorter-acting insulin before eating breakfast and dinner and a fixed dose of longer-acting insulin at bedtime.

Fixed regimens provide less flexibility, require a daily set schedule for meals, and have been largely replaced by basal-bolus regimens wherever possible.

In insulin pump.

Insulin pump therapy is increasingly being used in children. Potential benefits include better glucose control, safety, and user satisfaction compared to MDI regimens. This therapy is preferred for younger children, such as toddlers and preschoolers, and overall offers an added degree of control to many children.

use a fixed mixture of two forms of insulin: one that works quickly and lasts for only a few hours, and one that takes longer to work but lasts longer. The usual ratios of insulin are 70/30 (70% longer-acting and 30% shorter-acting) or 75/25. Children are given one injection at breakfast and one at dinner.

An advantage of premixed regimens is that they require fewer injections and are easier to manage. However, premixed regimens have less flexibility with respect to timing and amount of meals and cannot be adjusted as frequently. Thus, these regimens do not control blood glucose levels as well as other regimens.

Insulin can be injected in several ways:

• Vial and syringe

• Insulin pen

• Insulin pump

Some children use a vial and syringe. In this method, each dose of insulin is drawn up into a syringe from a vial and is injected under the skin, usually in the arm, thigh, or abdominal wall. Small syringes with very thin needles make the injections nearly painless. The amount of insulin the syringe will hold varies depending on the amount of insulin needed per injection. Young children often use syringes with 1/2 unit markings to allow for smaller adjustments in the doses of insulin to be used.

An insulin pen, is a convenient way for many children to carry and use insulin, especially for children who take several injections a day outside the home. The pen contains a cartridge that holds enough insulin for several doses. The dose delivered on each injection is adjusted by turning the top of the pen.

Another device is an insulin pump, which automatically pumps insulin continuously from a reservoir through a catheter that is left in the skin. The catheter site must be changed every 2 to 3 days. More and more children, even young children, are using insulin pumps. The pump more closely mimics the way the body normally delivers insulin. Pumps are programmed to release small doses of insulin continuously over 24 hours (called the basal dose) and can be triggered manually to deliver extra insulin (called the bolus dose) with meals or to treat high blood glucose. Unlike other methods, insulin pumps use only short-acting insulin. Children do not need longer-acting insulin because they are continually receiving a small amount of insulin in the basal dose. The pump can be programmed to give different amounts of insulin at different times of day and night.

Insulin pumps may be used with continuous glucose monitoring systems ( see Treatment) to better track trends in blood glucose throughout the day. Newer insulin pumps have been developed that combine insulin pump therapy with continuous glucose monitoring systems in one device.

Insulin Syringe and Insulin Pen

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Children with type 2 diabetes usually are not treated in the hospital unless the diabetes is severe. Usually they are given drugs to lower blood glucose levels (antihyperglycemic drugs) at a regular doctor's office visit. Children with severe diabetes may need to be hospitalized to start insulin treatment. Less commonly, children with type 2 diabetes develop severe dehydration or, as in type 1 diabetes, DKA.

is the main drug given by mouth (orally) for children and adolescents. It is started at a low dose and often increased over several weeks to higher doses. It can be taken with food to prevent nausea and abdominal pain.

and are injectable drugs that can be given to children over 10 years of age who have type 2 diabetes. These drugs may lower HbA1c levels and may also reduce appetite and promote weight loss. They may be given to children who are taking metformin but whose HbA1c level is not in the target range or they can be given instead of metformin to children who cannot tolerate that drug.

Other drugs used for adults with type 2 diabetes may help some adolescents, but they are more expensive, and there is limited evidence for their use in children.

is given to children who are hospitalized. Insulininsulin. About half of adolescents with type 2 diabetes ultimately require insulin.

Some children who lose weight, improve their food choices, and exercise regularly may be able to stop taking the drugs.

Low blood glucose (hypoglycemia) occurs when too much insulin or too much of an antihyperglycemic drug is taken or when the child does not eat regularly or exercises vigorously for a long period of time. Warning symptoms include confusion or other abnormal behavior, and children often appear pale and/or sweaty.

In adults, adolescents, and older children, episodes of hypoglycemia rarely cause long-term problems. However, frequent episodes of hypoglycemia in children younger than 5 years of age may impair intellectual development. Also, young children may not be aware of the warning symptoms of hypoglycemia. To minimize the possibility of hypoglycemia, doctors and parents monitor young children with diabetes particularly closely and use a slightly higher target range for their blood glucose level. Continuous glucose monitoring systems can help children because they sound an alarm when glucose falls below a specified range.

The frequency of monitoring depends on the type of diabetes.

In type 1 diabetes, blood glucose levels should be checked up to 6 to 10 times per day and should be measured before all meals and before a bedtime snack. A fingerstick glucose test is most often used to monitor blood glucose. Most blood glucose monitoring devices (glucose meters) use a drop of blood obtained by pricking a fingertip (fingerstick) with a small implement called a lancet. The lancet holds a tiny needle that can be jabbed into the finger or placed in a spring-loaded device that easily and quickly pierces the skin. The drop is placed on a test strip and the test strip is read by a machine. The machine reports the result on a digital display. Because exercise can lower glucose levels for up to 24 hours, glucose should be measured more frequently on days children exercise or are more active. Sometimes levels need to be measured during the night.

In type 2 diabetes, blood glucose levels should be measured regularly but typically less often than in type 1 diabetes. Several factors determine the frequency of self-monitoring, including children's glucose levels between meals and after eating. The frequency of monitoring should increase to at least 3 times a day if children do not have good control of their glucose, during illness, or when symptoms of hypoglycemia or hyperglycemia are felt. Once glucose is controlled, home testing is limited to a few between-meal and after-meal blood glucose measurements per week.

Once experience is gained, parents and many children can adjust the insulin dose as needed to achieve the best control. In general, by 10 years of age, children start to become interested in testing their own blood glucose levels and injecting insulin themselves. Parents should encourage this independence but make sure the child is being responsible. Doctors teach most children how to adjust their insulin dosage in accordance with the patterns of their home blood glucose records.

Children with either type of diabetes typically see their doctor several times a year. The doctor evaluates their growth and development, reviews blood glucose records that a family member keeps, provides guidance and counseling about nutrition, and measures glycosylated hemoglobin levels (hemoglobin A1C— see Diagnosing diabetes). The doctor usually screens for long-term complications of diabetes by measuring protein in the urine, doing tests to determine how the thyroid gland is functioning (thyroid function tests), doing tests to look for nerve damage, and doing eye examinations. Screening tests may be done once a year or every other year.

Continuous glucose monitoring (CGM) systems are an increasingly common method of monitoring blood glucose levels and can replace routine self-monitoring of blood glucose for some children. In CGM systems, a small glucose sensor placed under the skin measures blood glucose levels every 1 to 5 minutes, 24 hours a day. They transmit real-time results of blood glucose levels wirelessly to a device that may be built into an insulin pump or to a wireless monitor that can be worn on a belt. The systems also record results for the doctor to review. Alarms on CGM systems can be set to sound when blood glucose levels drop too low or climb too high, so the devices can help people quickly identify worrisome changes in blood glucose that they can treat right away. Use of CGM devices may help lower HbA1c levels.

Two types of CGM systems are currently available: real-time CGM and intermittently scanned CGM.

Real-time CGM can be used in children 2 years of age and older. This type of system automatically transmits a continuous stream of glucose data to the user in real time, provides alerts and active alarms, and also transmits glucose data to a receiver, smartwatch, or smartphone. Real-time CGM should be done as close to daily as possible for maximum benefit.

Intermittently scanned CGM can be used in children 4 years of age and older. This type of system provides the same type of glucose data as real-time CGM but requires the user to purposely scan the sensor to obtain information and does not have alerts and alarms. Intermittently scanned CGM should be done frequently, at least once every 8 hours. Children who use a CGM device need to be able to measure blood glucose with a fingerstick to calibrate their monitor and to verify glucose readings if they do not match their symptoms.

Although CGM devices can be used with any insulin regimen, they are typically worn by insulin pump users. When used in conjunction with an insulin pump, the combination is known as sensor-augmented pump therapy. This therapy requires manual adjustment of insulin doses based on CGM data results. Other CGM systems are integrated with a pump and can also lower the insulin dose if blood glucose drops too low. This integration can reduce the number of episodes where blood glucose drops too low, even when compared to sensor-augmented pump therapy.

Closed-loop insulininsulin pump to determine blood glucose levels and control insulin delivery. Current closed-loop systems are not truly automated because they require users to manually provide insulin for meals and snacks and make adjustments for exercise. These systems help to more tightly control insulin dosing and limit episodes where blood levels of insulin are too high or too low. A fully automated closed-loop system, sometimes known as an artificial pancreas, continues to be evaluated and is not commercially available.

Some children with diabetes do very well and control their diabetes without undue effort or conflict. In others, diabetes becomes a constant source of stress within the family, and control of the condition deteriorates. Adolescents may have particular problems controlling their blood glucose levels because of

• Hormonal changes during puberty: These changes affect how the body responds to insulin. As a result, higher doses are usually needed during this time.

• Adolescent lifestyle: Peer pressure, increased activities, erratic schedules, concern about body image, or eating disorders may interfere with the prescribed treatment regimen, particularly their meal plan.

• Experimentation with alcohol, cigarettes, and illicit drugs: Adolescents who experiment with these substances may neglect their treatment regimen and may be at greater risk of complications of diabetes (such as hypoglycemia and DKA).

• Conflicts with parents and other authority figures: Such conflicts may make adolescents less willing to follow their treatment regimen.

Thus, some adolescents need a parent or another adult to recognize these issues and give them the opportunity to discuss problems with a health care practitioner. The practitioner can help make sure adolescents remain appropriately focused on keeping their blood glucose levels under control. Parents and health care practitioners should encourage adolescents to check their blood glucose levels frequently.

An adolescent benefits if the doctor considers the adolescent’s desired schedule and activities and takes a flexible approach to problem solving by working with the adolescent rather than imposing solutions.

Mental health issues affect children with diabetes and their families ( see Mental health problems). The realization that they have a lifelong condition may cause some children to become sad or angry, and sometimes even deny that they have an illness. A doctor, psychologist, or counselor needs to address these emotions to secure the child’s cooperation in adhering to the required regimen of meal plan, physical activity, blood glucose testing, and drugs. Failure to resolve these issues can lead to difficulties controlling blood glucose.

Summer camps for children with diabetes allow these children to share their experiences with one another while learning how to become personally more responsible for their condition.

For the treatment of diabetes, the child’s primary care doctor usually enlists the aid of a team of other professionals, possibly including a pediatric endocrinologist, dietitian, diabetes educator, social worker, or psychologist. Family support groups may also help. The doctor may provide parents with information to bring to school so that school personnel understand their roles.