Adapted from American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care 34(suppl 1):62-69, 2011; and Botero D, Wolfsdorf JI: Diabetes mellitus in children and adolescents. Arch Med Res 2005;36:281-290.

Etiology and Pathogenesis

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) is the second most common chronic disease of childhood. It has two peaks in presentation, the first between 4 to 6 years of age and the second between 10 and 14 years (early puberty). Boys and girls are affected equally. T1DM most commonly affects whites of Northern European descent. T1DM is uncommon among blacks living in sub-Saharan Africa but is far more prevalent among U.S. black children of African descent.

T1DM can involve a genetic predisposition. Having a sibling with T1DM increases a person’s lifelong risk by 3% to 6%, a parent increases the risk by 2% to 5%, and a monozygotic twin increases the risk by 30% to 50%. T1DM also occurs more frequently among individuals who have other autoimmune disorders, such as Addison’s disease and Hashimoto’s thyroiditis. These diseases are associated with increased frequency of certain human leukocyte antigens of the major histocompatibility complex (MHC). It is currently believed that T1DM is caused by a “two-hit phenomenon.” An increased risk for T1DM is conferred via genes inherited in the MHC. Then, a second “hit” occurs after birth, activating the immune system and causing an immunologic attack on the pancreatic islets of Langerhans. Unfortunately, the nature of this second “hit” is not clear, and researchers have hypothesized that it may be caused by pregnancy-related and perinatal influences, viruses, vitamin D deficiency, or early ingestion of cow’s milk and cereals.

Over a period of time, T cells infiltrate the islets and cause β-cell destruction with consequent insulin deficiency. However, clinical symptoms do not generally occur until insulin secretory capacity is reduced to approximately 30% of normal, although the exact percentage is controversial. Most patients with T1DM have circulating autoantibodies against a variety of islet cells proteins, including islet cells, glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like protein (IA2), and insulin. These antibodies can be used to aid in diagnosis and as markers of risk. Of individuals who have the first three antibodies present, 50% will develop T1DM within 5 years.

Insulin is an anabolic hormone that stimulates glucose uptake and hepatic glycogen synthesis and inhibits hepatic gluconeogenesis and glycogenolysis. It also stimulates lipogenesis, amino acid uptake, and protein synthesis (see Chapter 4, Figure 4-1). The absence of insulin triggers a series of biochemical events that emulate a starvation state even when food intake is adequate and that result in hyperglycemia and ketoacidosis (Figures 71-1 and 4-2). Glucose uptake by peripheral tissues is reduced, and hepatic glycogenolysis and gluconeogenesis are stimulated by insulin deficiency, which produces hyperglycemia. Lipolysis, proteolysis, and fatty acid oxidation lead to the accumulation of ketone bodies (β-hydroxybutyrate and acetoacetate), which eventually leads to metabolic acidosis.

Figure 71-1 Insulin deprivation.

As the serum glucose increases above 180 mg/dL, the renal threshold for glucose reabsorption, glycosuria results. Glycosuria causes an osmotic diuresis, resulting in polyuria and compensatory polydipsia. Over time, hyperosmolarity and dehydration develop, and decreased tissue perfusion can elicit a mild lactic acidosis. Patients without free access to fluid, such as infants and those with developmental disorders, are especially at risk. The osmotic diuresis also leads to the loss of crucial electrolytes, such as sodium, potassium, phosphorus, magnesium, and calcium. Metabolic acidosis and dehydration also stimulate counterregulatory hormones, such as growth hormone, cortisol, and epinephrine, further antagonizing insulin action. The end result is a serious metabolic disorder termed diabetic ketoacidosis (DKA; see Chapter 4).

Type 2 Diabetes Mellitus

Although still rare in children and adolescents, type 2 diabetes mellitus (T2DM) has become more prevalent with the increase in pediatric obesity. T2DM results from a combination of genetic and environmental factors. Risk factors include obesity (particularly visceral adiposity), insulin resistance, race or ethnicity (Native Americans, African Americans, Hispanic, and Asian Americans are at greatest risk), family history (74%-100% have a first- or second-degree relative with T2DM), and physical inactivity. T2DM affects girls more often than boys, and children with T2DM often present during puberty, when there is a physiologic increase in insulin resistance.

Obesity increases insulin resistance, resulting in a compensatory hyperinsulinemia. Increased pancreatic insulin secretion cannot be sustained to meet demand, eventually resulting in a relative insulin deficiency and a loss of first-phase insulin secretion. The relative contributions of insulin resistance and the insulin secretory defect in T2DM are controversial.

Clinical Presentation

The clinical presentation of diabetes varies from asymptomatic hyperglycemia to life-threatening severe DKA. The majority of children with diabetes present with symptoms such as polyuria, polydipsia, nocturia, polyphagia, weight loss, dehydration, abdominal pain, vomiting, or lethargy. A history of secondary enuresis is not uncommon. Hyperglycemia and fluid compartment shifts can also affect the lens of the eye, causing blurry vision. The breakdown of protein and fat stores results in weight loss. Ketonemia can cause abdominal pain and vomiting. Pancreatitis can occur. A family history of other autoimmune diseases, such as thyroiditis and celiac disease, may be present.

Complicating the presentation is the fact that patients with new-onset diabetes often present during an intercurrent illness, which may confound the classic presentation of diabetes. In addition, a number of other conditions should be considered in the differential diagnosis of diabetes (Table 71-1).

Table 71-1 Differential Diagnosis

Symptom	Differential Diagnosis
Polyuria	Diabetes insipidus, urinary tract infection, psychogenic polydipsia
Polydipsia	Diabetes insipidus, psychogenic polydipsia
Glycosuria	Benign renal glycosuria
Weight loss	Anorexia nervosa, inflammatory bowel disease, celiac disease, infectious disease
Vomiting, abdominal pain	Gastroenteritis, inflammatory bowel disease, appendicitis, toxic ingestion, pancreatitis
Abnormal breathing	Pneumonia, asthma exacerbation
Hyperglycemia	Stress-induced hyperglycemia, medication-induced hyperglycemia

On physical examination, the respiratory status must be assessed first to determine the adequacy of the patient’s airway. Patients in DKA can present with tachypnea and deep, labored respirations called Kussmaul’s respirations. This breathing pattern occurs as respiratory compensation for the metabolic acidosis. It is important to evaluate a patient’s hydration status (tachycardia; hypotension; poor skin turgor; dry mucous membranes; sunken eyes; and in infants, sunken fontanelles), perfusion status (cool skin, delayed capillary refill), and mental status. The degree of dehydration (e.g., 5%, 10%, 20%) should be estimated, keeping in mind that intravascular fluids are preserved at the expense of intracellular fluids, and the physical examination will underestimate the degree of dehydration. Any abnormal cardiac findings should prompt immediate evaluation because electrolyte abnormalities in DKA can cause life-threatening arrhythmias. It is essential to fully evaluate neurocognitive status, with particular emphasis on mental status, because of the risk of cerebral edema.

The physical examination can disclose additional significant findings, such as a fruity breath odor secondary to ketoacidosis, candidal infections (particularly in the genital area) resulting from hyperglycemia, and nasopharyngeal infection (rhinocerebral mucormycosis). Pubertal status should be noted. Patients should also be examined for evidence of other autoimmune disorders, such as thyroiditis (goiter) and Addison’s disease (hyperpigmentation).

Type 2 Diabetes

The clinical presentation of T2DM in children can range from the incidental finding of glycosuria to severe acidosis or dehydration causing typical DKA. In addition to the signs described above for T1DM, children with T2DM often have specific characteristics that are related to insulin resistance, particularly obesity and acanthosis nigricans. In contrast to adults with T2DM, children with T2DM often have a shorter latency period of disease and commonly present with DKA. In addition, hyperglycemic hyperosmolar nonketotic coma (HHNK) is an extreme form of hyperosmolar dehydration seen more commonly in T2DM.

Evaluation and Management

Initial Evaluation

Well-Appearing Children

Initial biochemical evaluation of a patient suspected to have diabetes but not appearing ill should include a basic metabolic panel, including serum levels of electrolytes and glucose and urinalysis; a serum HbA1c can also be helpful. An oral glucose tolerance test is almost never necessary to diagnose T1DM but may be necessary for the early diagnosis of T2DM if the fasting blood glucose is not elevated. The American Diabetes Association (ADA) has established definitions for diabetes and increased risk for diabetes (prediabetes) (Box 71-2). Impaired glucose tolerance and impaired fasting glucose are both considered “prediabetes.” These conditions are more relevant for T2DM and require close follow-up. In 2010, the ADA added Hba1c diagnostic criteria for diabetes and prediabetes as well.

Box 71-2

American Diabetes Association Criteria

Criteria for diagnosis of diabetes:

1. Random blood glucose ≥200 mg/dL and symptoms of diabetes

2. Fasting plasma glucose ≥126 mg/dL *

3. 2-h glucose ≥200 mg/dL on an OGTT *

4. Hba1c ≥6.5% (must be performed using NGSP-certified method, standardized to DCCT assay)*

Criteria for diagnosis of prediabetes:

1. Fasting blood glucose: 100-125 mg/dL (impaired fasting glucose)

2. 2-h plasma glucose 140-199 mg/dL during a standard OGTT (impaired glucose tolerance)

3. Hba1c = 5.7−6.4%

DCTT, Diabetes Control and Complications Trial; NGSP, National Glycohemoglobin Standardization Program; OGTT, glucose tolerance test.

^* In absence of obvious hyperglycemia, confirm by repeat testing.

Adapted from American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care 34(suppl):S62-S69, 2011; American Diabetes Association: Standards of medical care in diabetes—2011. Diabetes Care 34(suppl):S11-S61, 2011.

Ill Children

For ill patients presenting with suspected diabetes, biochemical evaluation should include glucose, a comprehensive metabolic panel (including liver function tests), calcium, magnesium, phosphorus, venous or arterial (if respiratory compromise exists) blood gas, complete blood count (CBC) with differential, and urinalysis. In the case of potassium abnormalities, electrocardiography should be performed immediately. The serum sodium concentration is often low and is an unreliable measure of the degree of dehydration. This is partially because hyperglycemia causes osmotic movement of water into the extracellular space, thereby causing dilutional hyponatremia. Therefore, it is important to calculate the corrected sodium: for every 100 mg/dL of glucose over 100 mg/dL, the sodium concentration should be increased by 1.6 mEq/L [Measured sodium + ((Serum glucose − 100)/100) × 1.6].

DKA is common in patients with known T1DM, with a risk of about 1% to 10% per patient per year. In addition, about 25% of patients with new-onset diabetes present with DKA. DKA is present when a patient has marked hyperglycemia (glucose >300 mg/dL), ketonemia or ketonuria, and acidosis (pH<7.3 and bicarbonate <15 mEq/L). The details of evaluation and management of DKA are discussed in Chapter 4.

Children with new-onset diabetes and their families require intensive education with a multidisciplinary team of doctors, nurse practitioners, nutritionists, social workers, and case managers. When feasible, this is most effectively done while the child is still an inpatient. Additional screening laboratory tests should be performed to confirm the diagnosis of diabetes and screen for comorbidities. These tests include C-peptide, insulin (if not yet treated with insulin), HbA1c, diabetes autoimmune panel (see above), celiac screening antibodies, thyroid-stimulating hormone, thyroxine (T4), and antithyroid antibodies. In patients who fit the criteria for T2DM, liver function testing, fasting lipid panel, and urine microalbumin : creatinine ratio should also be obtained.

Post–Diabetic Ketoacidosis and Home Management

Type 1 Diabetes

Home management of children with diabetes involves careful balancing of insulin requirements with carbohydrate intake, exercise, and activity. Realistic blood glucose goals for children vary with age (Table 71-2). The risk of hypoglycemia in children who have hypoglycemia unawareness or lack the maturity to respond to the symptoms of hypoglycemia are limiting factors in setting goals for intensive diabetes management in pediatric patients. Goals for intensive management should be set with the family, taking into consideration the abilities of the family and restrictions of age and social circumstances.

Table 71-2 Goals for Diabetes Control

For their initial insulin regimen, children with diabetes are typically placed either on (1) a program of multiple daily injections (MDI) or (2) a basal and bolus program with injections or an insulin pump (see Figure 71-2). The MDI program generally consists of NPH (neutral protamine Hagedorn) insulin and a form of short-acting insulin (Table 71-3). In a basal and bolus program, either an insulin pump or a combination of long-acting insulin (Lantus or Levemir) and short-acting insulin is used. Which regimen is initiated is decided in consultation with the patient and family, taking into careful consideration the family’s schedule and lifestyle (Box 71-3).

Figure 71-2 Insulin delivery methods.

Table 71-3 Types of Insulin

Box 71-3 Selecting an Initial Insulin Regimen

Consider Lantus or Levemir with meal time short-acting insulin (Novolog/Humalog) if:

• Infant or toddler with unpredictable eating habits if an adult is available to give daytime injections at school or daycare

• Child with schedule that needs maximum flexibility

• Child who plans to quickly transition to pump therapy

• Do not consider if an adult is not available to give daytime injections at school or daycare

Consider “split-mixed” dosing of NPH and short-acting insulin if:

• Lantus or Levemir is not an option

• Child or parents have needle phobia

• Family needs a simpler program because of multiple competing demands

• Family has a set daily schedule for meal or snack times

• Daycare or school is uncooperative with the requirement for lunchtime injection

Consider premixed insulin if:

• Type 2 patient

• Type 1 patient who requires a much simpler program because of competing demands or intellectual impairment

• Insulin program is likely to be temporary (e.g., steroid-induced hyperglycemia)

• Any patient with vision or learning limitations

Determination of the initial insulin total daily dose (TDD) depends on the patient’s clinical presentation at diagnosis. In addition, within the first few weeks after diagnosis with T1DM, many patients have a decrease in their insulin requirements because of residual pancreatic β-cell function, referred to as the “honeymoon period.” This period can last from a few months up to 2 years. However, most children who are no longer making insulin need 0.7 to 1.0 U/kg/d. Children who present in DKA tend to require larger insulin doses than those children who present with mild hyperglycemia without acidosis (Table 71-4).

Table 71-4 Selecting Initial Total Daily Dose

Condition of Child	Insulin Dose (U/kg/day*)
DKA	0.8-1.0
Ketonuria or no DKA	0.5-0.7
Incidental	0.4-0.6

DKA, diabetic ketoacidosis.

* Adjust for age and puberty by adding up to 0.2 U/kg/d in pubertal children or subtracting 0.2 U/kg/d for preschool children.

For children started on MDI or on a basal and bolus program of Lantus or Levemir, after the TDD has been established, the clinician must divide the TDD between long- and short-acting insulin (Table 71-5). Children who are started on an MDI program receive NPH before eating breakfast, dinner, and bedtime and short-acting insulin (Humalog or Novolog) before eating breakfast and dinner. Additional short-acting insulin can be given at lunch or bedtime to cover high blood glucose levels or to cover additional carbohydrates that are not planned into this coverage scheme (Table 71-6). Children on a basal and bolus program with Lantus or Levemir must receive short-acting insulin with every meal and snack to cover any hyperglycemia, as well as the carbohydrate load. Lantus or Levemir is typically given at dinner or bedtime and must be given as a separate injection and not mixed with the short-acting insulin. In younger children, the basal insulin may be split in half and given every 12 hours.

Table 71-5 Splitting Basal and Bolus Doses

Table 71-6 Insulin : Carbohydrate Ratios and Correction Factors

Age	Insulin : CHO*	Correction
0-5	1 U/30 g	1 U/100-150 mg/dL
6-11	1 U/15 g	1 U/75 mg/dL
12+	1 U/8-10 g	1 U/50 mg/dL

CHO, carbohydrate.

* Insulin:CHO for children with no β-cell reserve (“non-honeymooning”). Children with some residual β-cell function require less insulin coverage for CHO.

A postmeal dosing scheme can be used to cover carbohydrates in young children who have unpredictable eating patterns. The blood glucose level should be checked before the meal to calculate the need for a correction dose. After the meal, the insulin dose based on the grams of carbohydrate eaten is added to the correction dose to determine the total dose of short-acting insulin (see Table 71-6). The delayed onset of insulin action in this dosing scheme is not ideal but may be used temporarily to manage food issues in young children.

Dietary management for most children involves carbohydrate counting, which has replaced the older exchange system. The goal of dietary management is to provide a balanced diet while covering carbohydrate loads with insulin. A thorough dietary assessment should be conducted to determine overall caloric and nutrient requirements. A good rule of thumb to determine the amount of calories a child needs is 1000 calories + (100 × Child’s age in years [from 3-13 years]), with additional calories added for children with significant weight loss. Placing newly diagnosed children on a standard meal plan with a constant carbohydrate load allows the clinician to work with the family to determine individual insulin-to-carbohydrate ratios (Table 71-7). These ratios allow the family much more flexibility with meals and snacks, particularly when the child is on a basal and bolus program. Efforts should be made to customize the meal plan to the child’s usual eating patterns before diagnosis. Tailoring the overall plan to lifestyle enhances the likelihood of long-term adherence.

Table 71-7 Carbohydrate Counts by Age Groups

Age (y)	Meals (g)	Snacks (g)
1-3	30	15
4-5	30-45	15-20
6-8	45	15-20
9-11	60	15-20
12-14	75	30
15+ Girls	60	30
15+ Boys	90	45

Exercise and activity levels in children must be incorporated into decisions about carbohydrates and insulin dosing. Exercise has an overall effect of decreasing blood glucose that may be immediate or delayed (≤24 hours). Patients aware of the effect of exercise on their blood sugar can increase their carbohydrate intake or decrease their insulin dose in anticipation of a planned sports event to prevent hypoglycemia. In some children, the initial effect of strenuous exercise may be an increase in the blood glucose because of an adrenaline effect. Good record keeping is an essential tool in understanding the effects of exercise and responding to these trends.

Hypoglycemia (blood glucose <70 mg/dL) is a critical complication that must be anticipated in all children who are managed with intensive insulin regimens. Most children will experience two to four mild hypoglycemic events per week. The risk of hypoglycemia must be balanced with the child’s ability to perceive and respond appropriately to low blood sugars. Mild hypoglycemia should be treated with 15 g of fast-acting carbohydrates. Treatment can be repeated in 10 minutes if the blood glucose remains below 80 mg/dL.

Families should be instructed in the use of a glucagon emergency kit to treat acute episodes of severe hypoglycemia by subcutaneous injection of glucagon. There are also commercially available over-the-counter products, including glucose gels and cake icing, that are useful aids for treating acute hypoglycemia orally when the child is in the care of someone who is not instructed in the use of glucagon (e.g., coaches, grandparents, scout leaders). A total of 15 g of gel or cake icing should be placed in the space between the gums and cheek where the product can be quickly absorbed through the buccal mucosa. Also available are glucose tablets (4 g of carbohydrate per tablet) that do not create the same temptation as candy and other foods. Medic Alert identification should be a standard expectation for all children with diabetes.

Educating families about ketone management (“sick day rules”) is crucial to prevent progression to DKA and consequent hospitalization. Urine should be tested routinely for ketones if the blood glucose is 240 mg/dL or above or if the patient is sick (irrespective of the patient’s blood glucose level). When ketones are present, additional short-acting insulin (10% of TDD) should be given every 2 to 3 hours. To prevent dehydration, patients should drink 1 oz of fluid for every year of age. If the patient’s blood glucose is less than 200 mg/dL and additional insulin is given because of ketones, the patient should be encouraged to drink carbohydrate-containing fluids to prevent hypoglycemia. The most common reason for ketonuria after the initial diagnosis is an intercurrent illness. Other factors contributing to ketonuria are insulin omission and an insulin dose that is inadequate for the child’s overall requirements (Figure 71-3).

Figure 71-3 Ketone management example.

Blood glucose levels should be measured before all meals and before bedtime snack; levels should also be checked at 2 AM when there are concerns about overnight safety. Information that should be recorded as families attempt to adjust insulin doses include:

• Blood glucose levels

• Insulin doses

• Carbohydrates (CHO): time and grams of CHO actually consumed

• Exercise: variations in overall activity level before that reading (e.g., 8-hour car ride, unexpected soccer practice)

• Any relevant factor that might explain variations in current reading (e.g., late or forgotten snack)

Accurate blood glucose documentation allows families to become proactive with day-to-day decision making about insulin, carbohydrates, and activity. For example, a child may require a lower NPH dose at dinner when there will be an evening soccer practice and a higher dose on days where the major evening activity will be homework. This level of insight can only be achieved through good record keeping and careful analysis.

It is important to verify the bolus insulin regimen before adjusting basal insulin. Consider adjusting the bolus insulin dose if the patient has recurrent postprandial hypoglycemia or hyperglycemia. Consider adjusting basal insulin if postprandial readings are in range but the patient has overall recurrent hyperglycemia or hypoglycemia that is not explained by variations in diet, exercise, or other factors. Adjust the dose of dinnertime (or bedtime) Lantus or Levemir to obtain fasting morning blood glucose levels that match the bedtime readings.

Type 2 Diabetes Mellitus

As in T1DM, the treatment goals in pediatric management of T2DM are aimed at normalizing blood glucose and avoiding hypoglycemia, with similar regimens to monitor blood glucose and ketones as in patients with T1DM.

An intensive management program must include lifestyle modification, with recommendations for improved nutrition and increased physical exercise when losing weight is necessary to improve insulin sensitivity. The American Academy of Pediatrics recommends at least 60 minutes of moderate to vigorous physical activity per day. Screen time (including sedentary activities such as television, computer use not related to school, video games, text messaging) should be less than 2 hours per day. The newer active video sports games and activities that require players to get up off the couch are preferred over more sedentary video games because these active games may increase energy expenditure as much as moderate-intensity exercise. Dietary changes should be made in consultation with a pediatric nutritionist. Simple steps to improve the diet include elimination of sugar-containing drinks (juice and soda), discouragement of skipping meals, avoidance of grazing on food throughout the day, controlling portion size, switching to low-fat foods, and increasing fiber intake through more fruits and vegetables.

Metformin is the only drug approved for the treatment of T2DM in children. Metformin improves insulin sensitivity, decreases hepatic glucose production, and facilitates weight loss. Common side effects include anorexia or nausea, bloating, gas, abdominal pain, and diarrhea. To avoid these problems, metformin therapy should be initiated with a lower dose that can be increased gradually to achieve a target dose of 1000 mg by mouth twice daily given with food. Rare side effects include lactic acidosis and megaloblastic anemia, and families should be counseled about concerning signs and symptoms. Liver transaminases, CBC with differential, and pregnancy tests in young women should be checked at baseline and monitored while on treatment. Patients on metformin who require contrast for imaging studies should discontinue metformin for 48 hours before and after the study to decrease the risk of lactic acidosis.

Insulin therapy should be initiated for children with T2DM who present with a more severe clinical profile (e.g., HbA1c >8.5%). Lantus, Levemir, or a combination insulin preparation (e.g., Humulin 70/30 insulin) can be used, starting at 1 U/kg/d. Humulin 70/30 is a mixture of 70% Human Insulin Isophane Suspension and 30% Human Insulin Injection (rDNA origin). It is an intermediate-acting insulin combined with the more rapid onset of action of regular human insulin. The duration of activity may last up to 24 hours after injection. In the absence of acidosis, metformin can be started as well.

Complications and Comorbidities

Children with T1DM and T2DM are at risk for the same long-term complications that adults with diabetes face. General guidelines for screening and treating diabetic comorbidities and complications have been published by the ADA. Microvascular complications of diabetes include diabetic retinopathy, nephropathy, and neuropathy. Macrovascular concerns include coronary artery disease, stroke, and peripheral vascular disease. The Diabetes Control and Complications Trial showed that intensive glucose management reduces the risk of developing these conditions. HbA1c should be monitored every 3 months. Clinicians should consider baseline screening for complications within the first year of diagnosis to uncover any preexisting abnormalities. Annual screening should begin for nephropathy and retinopathy after the child is 10 years of age or has had diabetes for 3 to 5 years. The clinician should determine whether a family history of cardiovascular risk factors exists and should monitor the patient’s blood pressure as part of routine care. Medical nutrition therapy (MNT) should be initiated for children with an elevated fasting low-density lipoprotein cholesterol level (≥100 mg/dL). If MNT fails, drug therapy may be necessary to minimize the risk of cardiovascular disease. Treatment with an angiotensin-converting enzyme inhibitor should also be considered for children with microalbuminuria or with persistently elevated blood pressure readings (>90th to 95th percentiles) who do not respond to lifestyle intervention.

Children with T1DM are also at higher risk for the development of other autoimmune disorders, particularly autoimmune thyroid disease and celiac disease. Consideration should be given to screening children at diagnosis and every 1 to 2 years.

Children with T2DM are often obese and are therefore at risk for the complications of obesity as well as diabetes (see Chapter 15). Polycystic ovarian syndrome (PCOS) and obstructive sleep apnea are important comorbidities of obesity and T2DM. PCOS should be considered in girls with irregular menses, hirsutism, or acne. Children with daytime somnolence, headaches, and snoring should be evaluated with a sleep study.