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Diabetes Mellitus in Children and Adolescents

By

Andrew Calabria

, MD, The Children's Hospital of Philadelphia

Last review/revision Aug 2022 | Modified Sep 2022
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Diabetes mellitus involves absence of insulin secretion (type 1) or peripheral insulin resistance (type 2), causing hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia, polyphagia, polyuria, and weight loss. Diagnosis is by measuring plasma glucose levels. Treatment depends on type but includes drugs that reduce blood glucose levels, diet, and exercise.

The types of diabetes mellitus (diabetes) in children are similar to those in adults, but psychosocial problems are different and can complicate treatment.

Type 1 diabetes is the most common type in children, accounting for two thirds of new cases in children of all ethnic groups. It is one of the most common chronic childhood diseases, occurring in 1 in 350 children by age 18; the incidence has recently been increasing, particularly in children < 5 years. Although type 1 can occur at any age, it typically manifests between age 4 years and 6 years or between 10 years and 14 years.

Monogenic forms of diabetes, previously termed maturity-onset diabetes of youth (MODY), are not considered type 1 or type 2 (although they are sometimes mistaken for them) and are uncommon (1 to 4% of cases).

Prediabetes is impaired glucose regulation resulting in intermediate glucose levels that are too high to be normal but do not meet criteria for diabetes. In obese adolescents, prediabetes may be transient (with reversion to normal in 2 years in 60%) or progress to diabetes, especially in adolescents who persistently gain weight. Prediabetes is associated with the metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), hypertension, abnormal fasting plasma glucose or insulin resistance, and dyslipidemia. Causes... read more (impaired glucose regulation, dyslipidemia, hypertension, obesity).

Etiology of Diabetes in Children and Adolescents

Most patients are categorized as having type 1 or type 2 diabetes, and this distinction is used to guide treatment. Classification is based on clinical history (age, family history, body habitus), presentation, and laboratory studies, including antibodies. However, this classification system does not fully capture the clinical heterogeneity of patients, and some patients cannot clearly be classified as having type 1 or type 2 diabetes at diagnosis. In both type 1 and type 2 diabetes, genetic and environmental factors can result in the progressive loss of beta-cell function that results in hyperglycemia.

In type 1 diabetes, the pancreas produces little to no insulin because of autoimmune destruction of pancreatic beta-cells, possibly triggered by an environmental exposure in genetically susceptible people. Close relatives are at increased risk of diabetes (about 15 times the risk of the general population), with overall incidence 4 to 8% (30 to 50% in monozygotic twins). Children with type 1 diabetes are at higher risk of other autoimmune disorders, particularly thyroid disease and celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more Celiac Disease . Inherited susceptibility to type 1 diabetes is determined by multiple genes (> 60 risk loci have been identified). Susceptibility genes are more common among some populations and explain the higher prevalence of type 1 diabetes in certain ethnic groups (eg, Scandinavians, Sardinians).

In type 2 diabetes, the pancreas produces insulin, but there are varying degrees of insulin resistance, and insulin secretion is inadequate to meet the increased demand caused by insulin resistance (ie, there is relative insulin deficiency). Onset often coincides with the peak of physiologic pubertal insulin resistance, which may lead to symptoms of hyperglycemia in previously compensated adolescents. The cause is not autoimmune destruction of beta-cells but rather a complex interaction between many genes and environmental factors, which differ among different populations and patients.

Although type 2 diabetes is different than type 1 diabetes, type 2 diabetes in children is also different than type 2 diabetes in adults. In children, decline in beta-cell function and development of diabetes-related complications are accelerated.

Risk factors for type 2 diabetes include

  • Obesity

  • Native American, Black, Hispanic, Asian American, and Pacific Islander heritage

  • Family history (60 to 90% have a 1st- or 2nd-degree relative with type 2 diabetes)

Monogenic forms of diabetes are caused by genetic defects that are inherited in an autosomal dominant pattern, so patients typically have one or more affected family members. Unlike type 1 and type 2 diabetes, there is no autoimmune destruction of beta-cells or insulin resistance. Onset is usually before age 25 years.

Pathophysiology of Diabetes in Children and Adolescents

In type 1 diabetes, lack of insulin causes hyperglycemia and impaired glucose utilization in skeletal muscle. Muscle and fat are then broken down to provide energy. Fat breakdown produces ketones, which cause acidemia and sometimes a significant, life-threatening acidosis (diabetic ketoacidosis Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with... read more [DKA]).

In type 2 diabetes, there is usually enough insulin function to prevent DKA at diagnosis, but children can sometimes present with DKA (up to 25%) or, less commonly, hyperglycemic hyperosmolar state Hyperosmolar Hyperglycemic State (HHS) Hyperosmolar hyperglycemic state is a metabolic complication of diabetes mellitus characterized by severe hyperglycemia, extreme dehydration, hyperosmolar plasma, and altered consciousness.... read more (HHS), also referred to as hyperosmolar hyperglycemic nonketotic syndrome (HHNK), in which severe hyperosmolar dehydration occurs. HHS most often occurs during a period of stress or infection, with nonadherence to treatment regimens, or when glucose metabolism is further impaired by drugs (eg, corticosteroids). Other metabolic derangements associated with insulin resistance can be present at diagnosis of type 2 diabetes and include

Atherosclerosis begins in childhood and adolescence and markedly increases risk of cardiovascular disease.

In monogenic forms of diabetes, the underlying defect depends on the type. The most common types are caused by defects in transcription factors that regulate pancreatic beta-cell function (eg, hepatic nuclear factor 4-alpha [HNF-4-α], hepatic nuclear factor 1-alpha [HNF-1-α]). In these types, insulin secretion is impaired but not absent, there is no insulin resistance, and hyperglycemia worsens with age. Another type of monogenic diabetes is caused by a defect in the glucose sensor, glucokinase. With glucokinase defects, insulin secretion is normal but glucose levels are regulated at a higher set point, causing fasting hyperglycemia that worsens minimally with age.

Pearls & Pitfalls

  • Despite the common misconception, diabetic ketoacidosis can occur in children with type 2 diabetes.

Symptoms and Signs of Diabetes in Children and Adolescents

In type 1 diabetes, initial manifestations vary from asymptomatic hyperglycemia to life-threatening diabetic ketoacidosis Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with... read more . However, most commonly, children have symptomatic hyperglycemia without acidosis, with several days to weeks of urinary frequency, polydipsia, and polyuria. Polyuria may manifest as nocturia, bed-wetting, or daytime incontinence; in children who are not toilet-trained, parents may note an increased frequency of wet or heavy diapers. About half of children have weight loss as a result of increased catabolism and also have impaired growth. Fatigue, weakness, candidal rashes, blurry vision (due to the hyperosmolar state of the lens and vitreous humor), and/or nausea and vomiting (due to ketonemia) may also be present initially.

In type 2 diabetes, the manifestation varies widely. Children are often asymptomatic or minimally symptomatic, and their condition may be detected only on routine testing. However, some children have a severe manifestation of symptomatic hyperglycemia, HHS, or, despite the common misconception, DKA.

Complications of diabetes in children

Diabetic ketoacidosis Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with... read more is common among patients with known type 1 diabetes; it develops in about 1 to 10% of patients each year, usually because they have not taken their insulin. Other risk factors for DKA include prior episodes of DKA, difficult social circumstances, depression or other psychiatric disturbances, intercurrent illness, and use of an insulin pump (because of a kinked or dislodged catheter, poor insulin absorption due to infusion site inflammation, or pump malfunction). Clinicians can help minimize the effects of risk factors by providing education, counseling, and support.

Mental health issues are very common among children with diabetes and their families. Up to half of children develop depression, anxiety, or other psychologic problems Overview of Mental Disorders in Children and Adolescents Although it is sometimes assumed that childhood and adolescence are times of carefree bliss, as many as 20% of children and adolescents have a diagnosable mental disorder that causes impairment... read more . Eating disorders Introduction to Eating Disorders Eating disorders involve a persistent disturbance of eating or of behavior related to eating that Alters consumption or absorption of food Significantly impairs physical health and/or psychosocial... read more are a serious problem in adolescents, who sometimes also skip insulin doses in an effort to control weight. Psychologic problems can also result in poor glycemic control by affecting children's ability to adhere to their dietary and/or drug regimens. Social workers and mental health professionals (as part of a multidisciplinary team) can help identify and alleviate psychosocial causes of poor glycemic control.

Vascular complications rarely are clinically evident in childhood. However, early pathologic changes and functional abnormalities may be present a few years after disease onset in type 1 diabetes; prolonged poor glycemic control is the greatest long-term risk factor for the development of vascular complications. Microvascular complications include diabetic nephropathy Diabetic Nephropathy In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more Diabetic Nephropathy , retinopathy Diabetic Retinopathy In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more Diabetic Retinopathy , and neuropathy Diabetic Neuropathy In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more Diabetic Neuropathy . Microvascular complications are more common among children with type 2 diabetes than type 1 diabetes and in type 2 diabetes may be present at diagnosis or earlier in the disease course. Although neuropathy is more common among children who have had diabetes for a long duration (≥ 5 years) and poor control (glycosylated hemoglobin [HbA1c] > 10%), it can happen in young children who have had diabetes for a short duration and good control. Macrovascular complications include coronary artery disease Overview of Coronary Artery Disease Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more Overview of Coronary Artery Disease , peripheral vascular disease Peripheral Arterial Disease Peripheral arterial disease (PAD) is atherosclerosis of the extremities (virtually always lower) causing ischemia. Mild PAD may be asymptomatic or cause intermittent claudication; severe PAD... read more Peripheral Arterial Disease , and stroke Overview of Stroke Strokes are a heterogeneous group of disorders involving sudden, focal interruption of cerebral blood flow that causes neurologic deficit. Strokes can be Ischemic (80%), typically resulting... read more Overview of Stroke .

Diagnosis of Diabetes in Children and Adolescents

  • Fasting plasma glucose level ≥ 126 mg/dL (≥ 7.0 mmol/L)

  • Random glucose level ≥ 200 mg/dL ( ≥ 11.1 mmol/L)

  • Glycosylated hemoglobin (HbA1c) ≥ 6.5% (≥ 48 mmol/mol)

  • Sometimes oral glucose tolerance testing

(For recommendations about diagnosis, see also the American Diabetes Association's 2022 standards of medical care in diabetes for children and adolescents and the International Society for Pediatric and Adolescent Diabetes' (ISPAD) 2018 guidelines for diabetes in children and adolescents.)

Diagnosis of diabetes in children

Diagnosis of diabetes and prediabetes is similar to that in adults, typically using fasting or random plasma glucose levels and/or HbA1c levels, and depends on the presence or absence of symptoms ( see Table: Diagnostic Criteria for Diabetes Mellitus and Impaired Glucose Regulation Diagnostic Criteria for Diabetes Mellitus and Impaired Glucose Regulation Diagnostic Criteria for Diabetes Mellitus and Impaired Glucose Regulation ). Diabetes may be diagnosed with the presence of classic symptoms of diabetes and blood glucose measurements. Measurements are random plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L) or fasting plasma glucose ≥ 126 mg/dL (≥ 7.0 mmol/L); fasting is defined as no caloric intake for 8 hours.

An oral glucose tolerance test is not required and should not be done if diabetes can be diagnosed by other criteria. When needed, the test should be done using 1.75 g/kg (maximum 75 g) glucose dissolved in water. The test may be helpful in children without symptoms or with mild or atypical symptoms and may be helpful in suspected cases of type 2 or monogenic diabetes.

The HbA1c criterion is typically more useful for diagnosing type 2 diabetes, and hyperglycemia should be confirmed. Although the HbA1c screening test is commonly used for the diagnosis of type 2 diabetes in children, the results of the test should be used with caution. Data promoting HbA1c as a screening test are derived from adults, and several studies have questioned its validity because of its poor sensitivity for identifying children with dysglycemia (prediabetes or diabetes mellitus). In children with hemoglobinopathies (eg, sickle cell disease), alternative measurements (eg, fructosamine) should be considered.

Table

Initial evaluation and testing

For patients suspected of having diabetes but who do not appear ill, initial testing should include a basic metabolic panel, including electrolytes and glucose, and urinalysis. For ill patients, testing also includes a venous or arterial blood gas, liver tests, and calcium, magnesium, phosphorus, and hematocrit levels.

Diagnosis of diabetes type

Additional tests should be done to confirm the type of diabetes, including

  • C-peptide and insulin (if not yet treated with insulin) levels

  • HbA1c levels (if not already done)

  • Tests for autoantibodies against pancreatic islet cell proteins

Autoantibodies include glutamic acid decarboxylase, insulin, insulinoma-associated protein, and zinc transporter ZnT8. More than 90% of patients with newly diagnosed type 1 diabetes have ≥ 1 of these autoantibodies, whereas the absence of antibodies strongly suggests type 2 diabetes. However, about 10 to 20% of children with the type 2 diabetes phenotype have autoantibodies and are reclassified as type 1 diabetes, because such children are more likely to require insulin therapy and are at greater risk of developing other autoimmune disorders.

Monogenic diabetes is important to recognize because treatment differs from type 1 and type 2 diabetes. The diagnosis should be considered in children with a strong family history of diabetes but who lack typical features of type 2 diabetes; that is, they have only mild fasting (100 to 150 mg/dL [5.55 to 8.32 mmol/L]) or postprandial hyperglycemia, are young and not obese, and have no autoantibodies or signs of insulin resistance (eg, acanthosis nigricans). Genetic testing is available to confirm monogenic diabetes. This testing is important because some types of monogenic diabetes can progress with age.

Testing for complications and other disorders

Patients with type 1 diabetes should be tested for other autoimmune disorders by measuring celiac disease antibodies Diagnosis Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more Diagnosis and thyroid-stimulating hormone, thyroxine, and thyroid antibodies Laboratory Testing of Thyroid Function The thyroid gland, located in the anterior neck just below the cricoid cartilage, consists of 2 lobes connected by an isthmus. Follicular cells in the gland produce the 2 main thyroid hormones... read more . Testing for thyroid disease and celiac disease should occur every 1 to 2 years thereafter. Other autoimmune disorders, such as primary adrenal insufficiency (Addison disease), rheumatologic disease (eg, rheumatoid arthritis, systemic lupus erythematosus, psoriasis), other gastrointestinal disorders (eg, inflammatory bowel disease, autoimmune hepatitis), and skin disease (eg, vitiligo), may also occur in children with type 1 diabetes but do not require routine screening.

Patients with type 2 diabetes should have liver tests, fasting lipid profile, and urine microalbumin:creatinine ratio done at the time of diagnosis because such children (unlike those with type 1 diabetes, in whom complications develop over many years) often have comorbidities, such as fatty liver, hyperlipidemia, and hypertension, at diagnosis. Children with clinical findings suggestive of complications should also be tested:

Screening for diabetes

Asymptomatic children ≤ 18 years of age who are at risk should be screened for type 2 diabetes or prediabetes by measuring HbA1c. This test should first be done at age 10 years or at onset of puberty, if puberty occurred at a younger age, and should be repeated every 3 years.

Children at risk include those who are overweight (body mass index > 85th percentile for age and sex, or weight for height > 85th percentile) and who have any 2 of the following:

Treatment of Diabetes in Children and Adolescents

  • Diet and exercise

  • For type 1 diabetes, insulin

  • For type 2 diabetes, metformin and sometimes insulin or liraglutide

(For recommendations about treatment, see also the American Diabetes Association's 2022 standards of medical care in diabetes for children and adolescents and the International Society for Pediatric and Adolescent Diabetes' (ISPAD) 2018 guidelines for diabetes in children and adolescents .)

Intensive education and treatment in childhood and adolescence may help achieve treatment goals, which are to normalize blood glucose levels while minimizing the number of hypoglycemic episodes and to prevent or delay the onset and progression of complications.

Poor glycemic control and increased hospitalization rates are associated with certain socioeconomic factors. In spite of advances in diabetes technology that have improved quality of care and glycemic control, not all patients have benefited, and low-income and non-Hispanic Black children remain at higher risk of complications and adverse outcomes because of poor glycemic control. Social determinants of health (eg, socioeconomic status, neighborhood and physical environment, food environment, health care, social context) may impact the ability to maintain optimal glycemic control in children with type 1 diabetes.

Lifestyle modifications

Lifestyle modifications that benefit all patients include

  • Eating regularly and in consistent amounts

  • Limiting intake of refined carbohydrates and saturated fats

  • Increasing physical activity

In general, the term diet should be avoided in favor of meal plan or healthy food choices. The main focus is on encouraging heart-healthy diets low in cholesterol and saturated fats.

In type 1 diabetes, the popularity of basal–bolus regimens and the use of carbohydrate counting (parents estimate the amount of carbohydrate in an upcoming meal and use that amount to calculate the preprandial insulin dose) has changed meal plan strategies. In this flexible approach, food intake is not rigidly specified. Instead, meal plans are based on the child's usual eating patterns rather than on a theoretically optimal diet to which the child is unlikely to adhere, and insulin dose is matched to actual carbohydrate intake. The insulin:carbohydrate ratio is individualized but varies with age, activity level, pubertal status, and length of time from initial diagnosis. Technologic advances have allowed for greater precision and customization of insulin doses. A good rule of thumb for age is

  • Birth to 5 years: 1 unit insulin per 30 g carbohydrate

  • 6 to 12 years: 1 unit insulin per 15 g carbohydrate

  • Adolescence: 1 unit insulin per 5 to 10 g carbohydrate

In type 2 diabetes, patients should be encouraged to lose weight and thus increase insulin sensitivity. A good rule of thumb to determine the amount of calories needed by a child age 3 to 13 years is 1000 calories + (100 × child's age in years). Simple steps to improve the diet and manage caloric intake include

  • Eliminating sugar-containing drinks and foods made of refined, simple sugars (eg, processed candies and high fructose corn syrups)

  • Discouraging skipping meals

  • Avoiding grazing on food throughout the day

  • Controlling portion size

  • Limiting high-fat, high-calorie foods in the home

  • Increasing fiber intake by eating more fruits and vegetables

Glucose and HbA1c target levels

Plasma glucose targets ( see Table: Glucose and HbA1c Target Levels in Children and Adolescents with Type 1 Diabetes Glucose and HbA1c Target Levels in Children and Adolescents with Type 1 Diabetes Glucose and HbA1c Target Levels in Children and Adolescents with Type 1 Diabetes ) are established to balance the need to normalize glucose levels with the risk of hypoglycemia. Patients beyond the honeymoon phase (ie, patients who no longer have residual beta-cell function) should try to have ≥ 50% of blood glucose levels in the normal range (70 to 180 mg/dL [3.9 to 10 mmol/L]) and < 10% below range.

Treatment goals should be individualized based on patient age, diabetes duration, access to diabetes technology (eg, insulin pumps, continuous monitoring systems), comorbid conditions, and psychosocial circumstances. The risk of hypoglycemia in children who have hypoglycemia unawareness or lack the maturity to recognize the symptoms of hypoglycemia can limit aggressive attempts to achieve treatment goals. A less stringent HbA1c target level (< 7.5% [< 58 mmol/mol]) should be considered for such patients, whereas a more stringent target level (< 6.5% [< 48 mmol/mol]) should be reserved for select patients in whom it can be achieved without significant hypoglycemia and without negative impacts on well-being.

HbA1c target levels for type 1 diabetes in children and adolescents have been lowered over time in an effort to reduce complications—lower HbA1c levels during adolescence and young adulthood are associated with a lower risk of vascular complications. An HbA1c target level of < 7% (< 53 mmol/mol) is appropriate for most children, but many children and adolescents do not meet this target.

An increased frequency of self-monitoring of blood glucose levels (up to 6 to 10 times per day) or use of a continuous glucose monitoring (CGM) system can improve HbA1c levels because patients are better able to adjust insulin for meals, have an improved ability to correct hyperglycemic values, and are potentially able to detect hypoglycemia earlier, which prevents overcorrection (ie, excessive carbohydrate intake as treatment for hypoglycemia, resulting in hyperglycemia). When used properly, intermittently scanned CGM in conjunction with insulin therapy can be used to replace self-monitoring of blood glucose.

HbA1c levels correlate well to the percentage of time that blood glucose levels remain in the normal range, termed the percentage time-in-range. Time-in-range is commonly used as a therapeutic goal to assess the efficacy of the insulin regimen in combination with HbA1c level. A 10% change in time-in-range corresponds to about a 0.8 percentage point change in HbA1c. For example, a time-in-range of 80% corresponds to an HbA1c level of 5.9% (41 mmol/mol), 70% corresponds to 6.7% (50 mmol/mol), 60% corresponds to 7.5% (58 mmol/mol), and 40% time-in-range corresponds to an HbA1c level of 9% (75 mmol/mol) (1 Treatment reference Diabetes mellitus involves absence of insulin secretion (type 1) or peripheral insulin resistance (type 2), causing hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ).

In addition to time-in-range, CGM provides information related to average sensor glucose, time-above-range (> 180 mg/dL [> 10 mmol/L]) and time-below-range (< 70 mg/dL [< 3.9 mmol/L]), glycemic variability, glucose management indicator, and information related to adherence (eg, active CGM time, days worn).

CGM metrics derived from use over the most recent 14 days are recommended to be used in conjunction with HbA1c level. CGM data can be reported in a standardized format. The ambulatory glucose profile (AGP) is a standardized report of the mean glucose, time-in-range, and time-below-range. When using the AGP to monitor glycemia, a goal of time-in-range of > 70% with a time-below-range of < 4% may be used as a glycemic control goal along with the goal of an HbA1c target of < 7% (< 53 mmol/mol). Another report is the glucose management indicator, which provides an estimated HbA1c from mean CGM glucose levels, preferably from ≥ 14 days of data.

HbA1c target levels for type 2 diabetes in children and adolescents are similar to targets in type 1 diabetes, ie < 7% (< 53 mmol/mol). Similar to type 1 diabetes, target fasting glucose levels in type 2 diabetes should be < 130 mg/dL (7.2 mmol/L). Children who fail to meet HbA1c and/or fasting glucose targets are candidates for intensified therapy (eg, with insulin, liraglutide). More stringent targets for HbA1c (< 6.5% [< 48 mmol/mol]) and fasting blood glucose (< 110 mg/dL [6.1 mmol/L]) may be considered in patients with shorter duration of diabetes and in those treated with lifestyle interventions or metformin alone who achieve significant weight reduction.

Table

Type 1 diabetes insulin regimens

Insulin is the cornerstone of management of type 1 diabetes. Available insulin formulations are similar to those used in adults ( see Table: Onset, Peak, and Duration of Action of Human Insulin Preparations* Onset, Peak, and Duration of Action of Human Insulin Preparations* Onset, Peak, and Duration of Action of Human Insulin Preparations* ). Insulin should be given before a meal, except in young children whose consumption at any given meal is difficult to predict. Dosing requirements vary by age, activity level, pubertal status, and length of time from initial diagnosis. Within a few weeks of initial diagnosis, many patients have a temporary decrease in their insulin requirements because of residual beta-cell function (honeymoon phase). This honeymoon phase can last from a few months up to 2 years, after which insulin requirements typically range from 0.7 to 1 unit/kg/day. During puberty, patients require higher doses (up to 1.5 units/kg/day) to counteract insulin resistance caused by increased pubertal hormone levels.

Types of insulin regimens include

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

  • Insulin pump therapy

  • Fixed forms of MDI regimen or premixed insulin regimen (less common)

Most people with type 1 diabetes should be treated with MDI regimens (3 to 4 injections per day of basal and prandial insulin) or insulin pump therapy as part of intensive insulin regimens with the goal of improving metabolic control.

A basal-bolus regimen is typically the preferred MDI regimen. In this regimen, children are given a daily baseline dose of insulin that is then supplemented by doses of short-acting insulin before each meal based on anticipated carbohydrate intake and on measured glucose levels. The basal dose can be given as a once-a-day injection (sometimes every 12 hours for younger children) of a long-acting insulin (glargine,detemir, or degludec), with supplemental boluses given as separate injections of rapid-acting insulin (usually aspart or lispro). Glargine, degludec, or detemir injections are typically given at dinner or bedtime and must not be mixed with short-acting insulin.

In insulin pump therapy, the basal insulin is delivered at a fixed or variable rate by a continuous subcutaneous infusion of rapid-acting insulin (CSII) through a catheter placed under the skin. Mealtime and correction boluses also are delivered via the insulin pump. The basal dose helps keep blood glucose levels in range between meals and at night. Using an insulin pump to deliver the basal dose allows for maximal flexibility; the pump can be programmed to give different rates at different times throughout the day and night.

Insulin pump therapy is increasingly being used in children because of the potential benefits of glycemic control, safety, and patient satisfaction compared to MDI regimens. This therapy is typically preferred for younger children (toddlers, preschoolers) and overall offers an added degree of control to many children. Others find wearing the pump inconvenient or develop sores or infections at the catheter site. Children must rotate their injection and pump sites to avoid developing lipohypertrophy. Lipohypertrophy is an accumulation of lumps of fatty tissue under the skin. The lumps occur at insulin injection sites that have been overused and can cause variation in blood glucose levels because they can prevent insulin from being absorbed consistently.

More fixed forms of MDI regimens are less commonly used. They can be considered if a basal-bolus regimen is not an option (eg, because the family needs a simpler regimen, the child or parents have a needle phobia, lunchtime injections cannot be given at school or daycare). In this regimen, children usually receive neutral protamine Hagedorn (NPH) insulin before eating breakfast and dinner and at bedtime and receive rapid-acting insulin before eating breakfast and dinner. Because NPH and rapid-acting insulin can be mixed, this regimen provides fewer injections than the basal-bolus regimen. However, this regimen provides less flexibility, requires a set daily schedule for meals and snack times, and has been largely supplanted by the analog insulins glargine and detemir because of the lower risk of hypoglycemia.

Premixed insulin regimens use preparations of 70/30 (70% insulin aspart protamine/30% regular insulin) or 75/25 (75% insulin lispro protamine/25% insulin lispro). Premixed regimens are not a good choice but are simpler and may improve adherence because they require fewer injections. Children are given set doses twice daily, with two thirds of the total daily dose given at breakfast and one third at dinner. However, premixed regimens provide much less flexibility with respect to timing and amount of meals and are less precise than other regimens because of the fixed ratios.

Clinicians should use the most intensive management program children and their family can adhere to in order to maximize glycemic control and thus reduce the risk of long-term vascular complications.

Type 1 diabetes management of complications

Hypoglycemia Hypoglycemia Hypoglycemia, or low plasma glucose level can result in sympathetic nervous system stimulation, and central nervous system dysfunction. In patients with diabetes who take insulin or antihyperglycemic... read more is a critical but common complication in children treated with an intensive insulin regimen. Most children have several mild hypoglycemic events per week and self-treat with 15 g of fast-acting carbohydrates (eg, 4 oz of juice, glucose tablets, hard candies, graham crackers, or glucose gel).

Severe hypoglycemia, defined as an episode requiring the assistance of another person to give carbohydrates or glucagon, occurs in about 30% of children each year, and most will have had such an episode by age 18. Oral carbohydrates may be tried, but glucagon 1 mg IM is usually used if neuroglycopenic symptoms (eg, behavioral changes, confusion, difficulty thinking) prevent eating or drinking. If untreated, severe hypoglycemia can cause seizures or even coma or death. Real-time continuous glucose monitoring devices can help children with hypoglycemia unawareness because they sound an alarm when glucose is below a specified range or when glucose declines at a rapid rate (see Monitoring glucose and HbA1c levels Monitoring glucose and HbA1c levels Diabetes mellitus involves absence of insulin secretion (type 1) or peripheral insulin resistance (type 2), causing hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ).

Ketonuria/ketonemia is most often caused by intercurrent illness but also can result from not taking enough insulin or from missing doses and can be a warning of impending DKA. Because early detection of ketones is crucial to prevent progression to DKA and minimize need for emergency department or hospital admission, children and families should be taught to check for ketones in the urine or capillary blood using ketone test strips. Blood ketone testing may be preferred in younger children, those with recurrent DKA, and insulin pump users or if a urine sample is difficult to obtain. Ketone testing should be done whenever the child become ill (regardless of the blood sugar level) or when the blood sugar is high (typically > 240 mg/dL [13.3 mmol/L]). The presence of moderate or large urine ketone levels or blood ketone levels > 1.5 mmol/L can suggest DKA, especially if children also have abdominal pain, vomiting, drowsiness, or rapid breathing. Small urine ketone levels or blood ketone levels 0.6 to 1.5 mmol/L also must be addressed.

When ketones are present, children are given additional short-acting insulin, typically 10 to 20% of the total daily dose, every 2 to 3 hours until ketones are cleared. Also, additional fluid should be given to prevent dehydration. This program of measuring ketones and giving additional fluid and insulin during illness and/or hyperglycemia is called sick-day management. Parents should be instructed to call their health care provider or go to the emergency department if ketones increase or do not clear after 4 to 6 hours, or if the clinical status worsens (eg, respiratory distress, continued vomiting, change in mental status).

Type 2 diabetes treatment

As in type 1 diabetes, lifestyle modifications, with improved nutrition and increased physical activity, are important.

Insulin is started in children who present with more severe diabetes (HbA1c > 9% [> 75 mmol/mol] or with DKA); glargine, detemir, or premixed insulin can be used. If acidosis is not present, metformin is usually started at the same time. Insulin requirements may decline rapidly during the initial weeks of treatment as endogenous insulin secretion increases; insulin often can be stopped several weeks after regaining acceptable metabolic control.

Metformin is an insulin sensitizer and is the only oral antihyperglycemic drug approved for patients < 18 years of age. Other oral drugs used in adults Oral Antihyperglycemic Drugs General treatment of diabetes mellitus for all patients involves lifestyle changes, including diet and exercise. Appropriate monitoring of blood glucose levels is essential to prevent complications... read more may benefit some adolescents, but they are more expensive, and there is limited evidence for their use in youth. Metformin should be started at a low dose and taken with food to prevent nausea and abdominal pain. A typical starting dose is 500 mg orally once a day for 1 week, which is increased weekly by 500 mg for 3 to 6 weeks until reaching the maximal target dose of 1000 mg 2 times a day. The goal of treatment is an HbA1c level of at least < 7% (< 53 mmol/mol), preferably < 6.5% (< 48 mmol/mol). If this cannot be achieved with metformin alone, basal insulin or liraglutide should be started. Unfortunately, about half of adolescents with type 2 diabetes ultimately fail metformin monotherapy and require insulin. If patients fail to meet targets using dual therapy with metformin and basal insulin, rapid-acting prandial insulin may also be added.

Liraglutide and extended-release exenatide are glucagon-like peptide-1 (GLP-1) receptor agonists approved for use in children > 10 years of age with type 2 diabetes and can help reduce HbA1c levels. These injectable noninsulin antihyperglycemic drugs enhance glucose-dependent insulin secretion and slow gastric emptying. Liraglutide is started at 0.6 mg subcutaneously once a day and may be increased weekly by 0.6 mg until control is adequate up to 1.8 mg once a day. Extended-release exenatide dose is 2 mg subcutaneously once/week, which may improve patient adherence. Both drugs promote weight loss, likely through the effect of delayed gastric emptying and appetite reduction. The most common adverse effects of GLP-1 agonists are gastrointestinal, especially nausea and vomiting. Liraglutide and exenatide can be used if metformin is not tolerated or added on if HbA1c target levels are not achieved with metformin alone within 3 months. Liraglutide and exenatide can be used in place of or in combination with insulin as part of intensive treatment of type 2 diabetes.

Monogenic diabetes treatment

Management of monogenic diabetes is individualized and depends on subtype. The glucokinase subtype generally does not require treatment because children are not at risk of long-term complications. Most patients with hepatic nuclear factor 4-alpha and hepatic nuclear factor 1-alpha types are sensitive to sulfonylureas, but some ultimately require insulin. Other oral hypoglycemics such as metformin are typically not effective.

Monitoring glucose and HbA1c levels

Routine monitoring involves

  • Multiple daily glucose checks by fingerstick or continuous glucose monitoring

  • HbA1c measurements every 3 months

In type 1 diabetes, blood glucose levels should be monitored 6 to 10 times per day by using a glucose meter or a continuous glucose monitoring (CGM) system to optimize control. Traditionally, glucose levels should be measured using a fingerstick sample before all meals and before a bedtime snack. Levels also should be checked during the night (around 2 to 3 AM) if nocturnal hypoglycemia is a concern (eg, because of hypoglycemia or vigorous exercise during the day, or when an insulin dose is increased). Because exercise can lower glucose levels for up to 24 hours, levels should be checked more frequently on days when children exercise or are more active. To prevent hypoglycemia, children may increase carbohydrate intake or lower insulin dosing when they anticipate increased activity. Sick-day management should be used with hyperglycemia or illness.

Parents should keep detailed daily records of all factors that can affect glycemic control, including blood glucose levels; timing and amount of insulin doses, carbohydrate intake, and physical activity; and any other relevant factors (eg, illness, late snack, missed insulin dose).

Patients with type 2 diabetes usually self-monitor blood glucose levels less frequently than patients with type 1 diabetes, but frequency varies depending on the type of drug therapy used. Children and adolescents taking multiple daily insulin injections, those who are ill, and those with suboptimal control should monitor glucose levels at least 3 times a day. Those who are on stable regimens of metformin and only long-acting insulin, who are meeting their targets without hypoglycemia, can monitor less frequently, typically twice a day (fasting and 2 hours postprandial). Children and adolescents with type 2 diabetes on insulin regimens with multiple daily injections sometimes use continuous glucose monitoring systems.

In type 2 diabetes, blood glucose levels should be measured regularly but typically less often than in type 1 diabetes. The frequency of self-monitoring of blood glucose should be individualized based on the patient's fasting and postprandial glucose levels, the degree of glycemic control deemed achievable, and the available resources. The frequency of monitoring should increase if glycemic control targets are not being met, during illness, or when symptoms of hypoglycemia or hyperglycemia are felt. Once targets are achieved, home testing is limited to a few fasting and postprandial blood glucose measurements per week.

HbA1c levels should be measured every 3 months in type 1 diabetes and in type 2 diabetes if insulin is being used or metabolic control is suboptimal. Otherwise, in type 2 diabetes, levels can be measured twice a year, although every 3 months is optimal.

Continuous glucose monitoring (CGM) systems are a common method (> 60% of children use one) of monitoring blood glucose levels and can replace routine self-monitoring of blood glucose for some patients. They are a more sophisticated and effective approach to monitoring that uses a subcutaneous sensor to measure interstitial fluid glucose levels every 1 to 5 minutes and then translate the measurements into blood glucose values, thus more closely detecting glucose fluctuations that can then be acted upon in real time. CGM systems transmit results wirelessly to a monitoring and display device that may be built into an insulin pump or may be a stand-alone device. By identifying times of consistent hyperglycemia and times of increased risk of hypoglycemia, CGM systems can help patients with type 1 diabetes more safely reach glycemic goals.

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. The 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 used as close to daily as possible for maximal benefit. Intermittently scanned CGM can be used in children ≥ 4 years of age. It 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 used frequently, a minimum of once every 8 hours. Children using CGM devices need to be able to measure blood glucose by fingerstick to calibrate their monitor and/or to verify readings if they are discordant from symptoms.

Compared to intermittent monitoring, CGM systems can help lower HbA1c levels, increase the percentage of time-in-range, and lower the risk of hypoglycemia.

Although CGM devices can be used with any 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 results. Other CGM systems are integrated with a pump and can also suspend the basal rate for up to 2 hours when glucose levels drop below a set threshold. This integration can reduce the number of hypoglycemic events, even when compared to sensor-augmented pump therapy.

Closed-loop insulin pumps can be used in children ≥ 2 years of age. These hybrid closed-loop systems automate blood glucose management through sophisticated computer algorithms that are on a smartphone or similar device and link a CGM sensor to an insulin pump to determine blood glucose levels and control insulin delivery. Delivery is controlled by suspending, increasing, or decreasing basal insulin in response to CGM values. Current hybrid closed-loop systems are not truly automated because they require users to administer a bolus for meals and snacks. These systems help more tightly control insulin dosing and limit hyperglycemic and hypoglycemic episodes. A fully automated closed-loop system, sometimes known as a bihormonal (insulin and glucagon) artificial pancreas, continues to be evaluated and is not commercially available.

Screening for complications of diabetes

Patients are screened regularly for complications depending on the type of diabetes ( see Table: Screening Children for Complications of Diabetes Screening Children for Complications of Diabetes Screening Children for Complications of Diabetes ). If complications are detected, subsequent testing is done more frequently.

Table

Complications detected on examination or screening are treated first with lifestyle interventions: increased exercise, dietary changes (particularly limiting saturated fat intake), and cessation of smoking (if applicable). Children with microalbuminuria (albumin/creatinine ratio 30 to 300 mg/g) on repeat samples or with persistently elevated blood pressure readings Hypertension in Children Hypertension is sustained elevation of resting systolic blood pressure, diastolic blood pressure, or both; the pressures considered abnormal in children vary based on age up to age 13. Hypertension... read more (> 90th to 95th percentiles for age or ≥ 130/80 mm Hg for adolescents) who do not respond to lifestyle interventions typically require antihypertensive therapy, most commonly using an angiotensin-converting enzyme inhibitor. For children with dyslipidemia, if low-density lipoprotein (LDL) cholesterol remains > 160 mg/dL (4.14 mmol/L) or > 130 mg/dL (3.37 mmol/L) and one or more cardiovascular risk factors remain despite lifestyle interventions, statins should be considered in children > 10 years, although long-term safety is not established.

Treatment reference

  • 1. Beck RW, Bergenstal RM, Cheng P, et al: The relationships between time in range, hyperglycemia metrics, and HbA1c. Diabetes Technol Ther 13(4):614–626, 2019. doi: 10.1177/1932296818822496

Key Points

  • Type 1 diabetes is caused by an autoimmune attack on pancreatic beta-cells, causing complete lack of insulin; it accounts for two thirds of new cases in children and can occur at any age.

  • Type 2 diabetes is caused by insulin resistance and relative insulin deficiency due to a complex interaction among many genetic and environmental factors (particularly obesity); it is increasing in frequency in children and occurs after puberty.

  • Most children have symptomatic hyperglycemia without acidosis, with several days to weeks of urinary frequency, polydipsia, and polyuria; children with type 1 diabetes and rarely type 2 diabetes may present with diabetic ketoacidosis.

  • Screen asymptomatic, at-risk children for type 2 diabetes or prediabetes.

  • All children with type 1 diabetes require insulin treatment; intensive glycemic control helps prevent long-term complications but increases risk of hypoglycemic episodes.

  • Advances in diabetes technology, such as continuous glucose monitoring systems, are aimed at improving glycemic control while reducing hypoglycemic episodes.

  • Children with type 2 diabetes are initially treated with metformin and/or insulin; although most children requiring insulin at diagnosis can be successfully transitioned to metformin monotherapy, about half eventually require insulin treatment.

  • Liraglutide can be used in combination with metformin to improve glycemic control.

  • Mental health issues are common among children with diabetes and can be associated with poor glycemic control.

  • Insulin doses are adjusted based on frequent glucose monitoring and anticipated carbohydrate intake and activity levels.

  • Children are at risk of microvascular and macrovascular complications of diabetes, which must be sought by regular screening tests.

More Information

The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

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NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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