• The need for and extent of laboratory studies vary, depending upon the general state of the child's health. For most children, only urine testing for glucose and blood glucose measurement are required for a diagnosis of diabetes. Other conditions associated with diabetes require several tests at diagnosis and at later review. (See Diabetic Ketoacidosis for information on laboratory studies needed to manage cases of DKA.)
• Urine glucose
• • A positive urine glucose test suggests but is not diagnostic for IDDM. Diagnosis must be confirmed by test results showing elevated blood glucose levels.
  • Test urine of ambulatory patients for ketones at the time of diagnosis.
• Urine ketones
• • Ketones in the urine confirm lipolysis and gluconeogenesis, which are normal during periods of starvation.
  • With hyperglycemia and heavy glycosuria, ketonuria is a marker of insulin deficiency and potential DKA.
• Blood glucose
• • Apart from transient illness- or stress-induced hyperglycemia, a random whole-blood glucose concentration more than 200 mg/dL (11 mmol/L) is diagnostic for diabetes, as is a fasting whole-blood glucose concentration exceeding 120 mg/dL (7 mmol/L). In the absence of symptoms, the physician must confirm these results on a different day. Most children with diabetes detected because of symptoms have a blood glucose level of at least 250 mg/dL (14 mmol/L).
  • Blood glucose tests using capillary blood samples, reagent sticks, and blood glucose meters are the usual methods for monitoring day-to-day diabetes control.
• Glycated hemoglobin
• • Glycosylated hemoglobin derivatives (HbA1a, HbA1b, HbA1c) are the result of a nonenzymatic reaction between glucose and hemoglobin. A strong correlation exists between average blood-glucose concentrations over an 8- to 10-week period and the proportion of glycated hemoglobin. The percentage of HbA1c is more commonly measured. Normal values vary according to the laboratory method used, but nondiabetic children generally have values in the low-normal range. At diagnosis, diabetic children unmistakably have results above the upper limit of the reference range.
  • Measurement of HbA1c levels is the best method for medium- to long-term diabetic control monitoring. The Diabetes Control and Complications Trial (DCCT) has demonstrated that patients with HbA1c levels around 7% had the best outcomes relative to long-term complications. Check HbA1c levels every 3 months. Most clinicians aim for HbA1c values of 7-9%. Values less than 7% are associated with an increased risk of severe hypoglycemia; values more than 9% carry an increased risk of long-term complications.
• Renal function tests: If the child is otherwise healthy, renal function tests are typically not required.
• Islet cell antibodies
• • Islet cell antibodies may be present at diagnosis but are not needed to diagnose IDDM.
  • Islet cell antibodies are nonspecific markers of autoimmune disease of the pancreas and have been found in as many as 5% of unaffected children. Other autoantibody markers of type 1 diabetes are known, including insulin antibodies. More antibodies against islet cells are known (eg, those against glutamate decarboxylase [GAD antibodies]), but these are generally unavailable for routine testing.
• Thyroid function tests
• • Because early hypothyroidism has few easily identifiable clinical signs in children, children with IDDM may have undiagnosed thyroid disease.
  • Untreated thyroid disease may interfere with diabetes management. Check thyroid function regularly (every 2-5 years or annually if thyroid antibodies are present).
• Antithyroid antibodies: This test indicates risk of present or potential thyroid disease.
• Antigliadin antibodies
• • Some children with IDDM may have or develop celiac disease. Positive antigliadin antibodies, especially specific antibodies (eg, antiendomysial, antitransglutaminase) are important risk markers.
  • If antibody tests are positive, a jejunal biopsy is required to confirm or refute a diagnosis of celiac disease.

• Oral glucose tolerance test (OGTT)
• • While unnecessary to diagnose IDDM, an OGTT can exclude the diagnosis of diabetes when hyperglycemia or glycosuria are recognized in the absence of typical causes (eg, intercurrent illness, steroid therapy) or when the patient's condition includes renal glucosuria.
  • Obtain a fasting blood sugar level, then administer a PO glucose load (2 g/kg for children aged <3>10 y). Check the blood glucose concentration again after 2 hours. A fasting whole-blood glucose level higher than 120 mg/dL (6.7 mmol/L) or a 2-hour value higher than 200 mg/dL (11 mmol/L) indicates diabetes. Mild elevations, however, may not indicate diabetes when the patient has no symptoms and no diabetes-related antibodies.
  • A modified OGTT can also be used to identify cases of MODY that often present as type 1 diabetes, if, in addition to blood glucose levels, insulin or c-peptide (insulin precursor) levels are measured at fasting, 30 minutes, and 2 hours. Type 1 diabetics cannot produce more than tiny amounts of insulin. People with MODY or type 2 diabetes show variable and substantial insulin production in the presence of hyperglycemia.
• Lipid profile
• • Lipid profiles are usually abnormal at diagnosis because of increased circulating triglycerides caused by gluconeogenesis.
  • Apart from hypertriglyceridemia, primary lipid disorders rarely result in diabetes.
  • Hyperlipidemia with poor metabolic control is common.
• Urinary albumin: Beginning at age 12 years, perform an annual urinalysis to test for a slightly increased albumin excretion rate (AER), referred to as microalbuminuria, which is an indicator of risk for diabetic nephropathy.

• All children with IDDM require insulin therapy.
• Only children with significant dehydration, persistent vomiting, or metabolic derangement, or with serious intercurrent illness, require inpatient management and intravenous rehydration.
• A well-organized diabetes care team can provide all necessary instruction and support in an outpatient setting. The only immediate requirement is to train the child or family to check blood glucose levels, to administer insulin injections, and to recognize and treat hypoglycemia. The patient and/or family should have 24-hour access to advice and know how to contact the team.

• Always involve an experienced dietitian in the patient's care, typically as a regular member of the diabetes care team.
• Ophthalmology review may be needed at diagnosis if a cataract is suspected. All children with diabetes aged 12 years and older need a careful annual eye examination, either by direct ophthalmoscopy or high-quality retinal photography to identify and, if necessary, treat diabetes-related eye complications.
• Access to psychological counseling and support is desirable, preferably from a member of the diabetes care team.

Diet

Dietary management is an essential component of diabetes care. Diabetes is an energy metabolism disorder, and before insulin was discovered, children with diabetes could be kept alive by a diet severely restricted in carbohydrate and energy intake. These measures led to a long tradition of strict carbohydrate control and unbalanced diets. More recent dietary management of diabetes emphasizes a healthy, balanced diet, high in carbohydrates and fiber and low in fat.

• The following are universal recommendations:
• • Carbohydrates should provide 50-60% of daily energy intake. (No more than 10% of carbohydrates should be from sucrose or other refined carbohydrates.)
  • Fat should provide less than 30%.
  • Protein should provide 10-20%.
  • View these recommendations in the patient's cultural context.
• The aim of dietary management is to balance the child's food intake with insulin dose and activity and to keep blood glucose concentrations as close as possible to reference ranges, avoiding extremes of hyperglycemia and hypoglycemia.
• The ability to estimate the carbohydrate content of food (carb counting) is particularly useful for those children who give fast-acting insulin at meal times either by injection or insulin pump, as it allows for a more precise matching of food and insulin.
• • Adequate intake of complex carbohydrates (eg, cereals) is important before bedtime to avoid nocturnal hypoglycemia, especially for children having twice-daily injections of mixed insulin.
  • The dietitian should develop a diet plan for each child to suit individual needs and circumstances. Regularly review and adjust the plan to accommodate the patient's growth and lifestyle changes.
  • Low-carbohydrate diets as a management option for diabetes control have regained popularity in recent years. Logic dictates that the lower the carbohydrate intake, the less insulin is required. No trials of low-carbohydrate diets in children with type 1 diabetes have been reported, and such diets cannot be recommended at the present.

• IDDM requires no restrictions on activity; exercise has real benefits for a child with diabetes.
• Most children can adjust their insulin dosage and diet to cope with all forms of exercise.
• Children and their caretakers must be able to recognize and treat symptoms of hypoglycemia.
• • Hypoglycemia following exercise is most likely after prolonged exercise involving the legs, such as walking, running or cycling. It may occur many hours after exercise has finished and even affect insulin requirements the following day.
  • A large presleep snack is advisable following intensive exercise.

• Hypoglycemia
  • Hypoglycemia is probably the most disliked and feared complication of diabetes, from the point of view of the child and the family. Children hate the symptoms of a hypoglycemic episode and the loss of personal control it may cause.
  • Insulin inhibits glucogenesis and glycogenolysis, while stimulating glucose uptake. In nondiabetic individuals, insulin production by the pancreatic islet cells is suppressed when blood glucose levels fall below 83 mg/dL (4.6 mmol/L). If insulin is injected in a treated diabetic child who has not eaten adequate amounts of carbohydrates, blood glucose levels progressively fall.
  • The brain depends upon glucose as a fuel. As glucose levels drop below 65 mg/dL (3.2 mmol/L) counterregulatory hormones (eg, glucagon, cortisol, epinephrine) are released, and symptoms of hypoglycemia develop. These symptoms include sweatiness, shaking, confusion, behavioral changes, and, eventually, coma when blood glucose levels fall below 30-40 mg/dL. The glucose level at which symptoms develop varies greatly from individual to individual (and from time to time in the same individual), depending in part on the duration of diabetes, frequency of hypoglycemic episodes, rate of fall of glycemia, and overall control.
  • Manage mild hypoglycemia by giving rapidly absorbed PO carbohydrate or glucose; for a comatose patient, administer an intramuscular injection of the hormone glucagon, which stimulates the release of liver glycogen and releases glucose into the circulation. Where appropriate, an alternative therapy is intravenous glucose (preferably no more than a 10% glucose solution). All treatments for hypoglycemia provide recovery in approximately 10 minutes.
  • Occasionally, a child with hypoglycemic coma may not recover within 10 minutes, despite appropriate therapy. Under no circumstances should further treatment be given, especially intravenous glucose, until the blood glucose level is checked and still found subnormal. Overtreatment of hypoglycemia can lead to cerebral edema and death. If coma persists, seek other causes.
  • Hypoglycemia is a particular concern in children younger than 4 years because the condition may lead to possible intellectual impairment later in life.
• Hyperglycemia
  • In an otherwise healthy individual, blood glucose levels usually do not rise above 180 mg/dL (9 mmol/L). In a child with diabetes, blood sugar levels rise if insulin is insufficient for a given glucose load. The renal threshold for glucose reabsorption is exceeded when blood glucose levels exceed 180 mg/dL (10 mmol/L), causing glycosuria with the typical symptoms of polyuria and polydipsia.
  • All children with diabetes experience episodes of hyperglycemia.
• Diabetic ketoacidosis
  • DKA is much less common than hypoglycemia, but it is potentially far more serious, creating a life-threatening medical emergency.
  • Ketosis usually does not occur when insulin is present. In its absence, however, severe hyperglycemia, dehydration, and ketone production contribute to the development of DKA.
• DKA usually follows increasing hyperglycemia and symptoms of osmotic diuresis. Users of insulin pumps, by virtue of absent reservoirs of subcutaneous insulin, may present with ketosis and more normal blood glucose levels. They are more likely to present with nausea, vomiting, and abdominal pain, symptoms similar to food poisoning.
• Injection-site hypertrophy
  • If children persistently inject their insulin into the same area, subcutaneous tissue swelling may develop, causing unsightly lumps and adversely affecting insulin absorption. Rotating the injection sites resolves the condition.
  • Fat atrophy can also occur, possibly in association with insulin antibodies. This condition is much less common but more disfiguring.
• Diabetic retinopathy
  • The most common cause of acquired blindness in many developed nations, diabetic retinopathy is rare in the prepubertal child or within 5 years of onset of diabetes.
  • Prevalence and severity of retinopathy increases with age and is greatest in patients whose diabetic control is poor. Prevalence rates seem to be declining, yet an estimated 80% of people with IDDM develop retinopathy.
  • Diabetic retinopathy's first symptoms are dilated retinal venules and the appearance of capillary microaneurysms, a condition known as background retinopathy. These changes may be reversible or their progression may be halted with improved diabetic control, although some patient's conditions may worsen initially.
  • Subsequent changes in background retinopathy are characterized by increased vessel permeability and leaking plasma that form hard exudates, followed by capillary occlusion and flame-shaped hemorrhages. The patient may not notice these changes unless the macula is involved. Laser therapy may be required at this stage to prevent further visual loss. Proliferative retinopathy follows with further vascular occlusion, retinal ischemia, proliferation of new retinal blood vessels and fibrous tissue, then progressing to hemorrhage, scarring, retinal detachment, and blindness. Prompt retinal laser therapy may prevent blindness in the later stages, so regular screening is vital.
• Diabetic nephropathy and hypertension
  • Diabetic nephropathy's exact mechanism is unknown. Peak incidence is in postadolescents, 10-15 years after diagnosis, and may involve up to 30% of people with IDDM.
  • Microalbuminuria is the first evidence of nephropathy. The exact definition varies slightly between nations but an increased AER is commonly defined as a ratio of first morning–void urinary albumin levels to creatinine levels that exceeds 10 mg/mmol, or as a timed overnight AER of more than 20 mcg/min but less than 200 mcg/min. Early microalbuminuria may resolve. Glomerular hyperfiltration occurs, as do abnormalities of the glomerular basement membrane and glomeruli.
  • In a patient with nephropathy, AER increases until frank proteinuria develops, and this may progress to renal failure. Blood pressure rises with increased AER, and hypertension accelerates the progression to renal failure.
  • Progression may be delayed or halted by improved diabetes control, by administration of angiotensin-converting enzyme inhibitors (ACE inhibitors), and by aggressive blood pressure control.
  • Regular urine screening for microalbuminuria provides opportunities for early identification and treatment to prevent renal failure.
• A child younger than 15 years with persistent proteinuria may have a nondiabetic cause and should be referred to a pediatric nephrologist for further assessment.
• Diabetic neuropathy affects both the peripheral and autonomic nerves. Hyperglycemic effects on axons and microvascular changes in endoneural capillaries are amongst the proposed mechanisms.
• Autonomic changes involving cardiovascular control (eg, heart rate, postural responses) have been described in as many as 40% of children with diabetes. Cardiovascular control changes become more likely with increasing duration and worsening control.
• In adults, peripheral neuropathy usually occurs as a distal sensory loss.

• Macrovascular disease

• While this complication is not seen in pediatric patients, it is a significant cause of morbidity and premature mortality in adults with diabetes.
• People with IDDM have twice the risk of fatal myocardial infarction (MI) and stroke than people unaffected with diabetes; for women, the MI risk is 4 times greater. People with IDDM also have 4 times greater risk for atherosclerosis.
• The combination of peripheral vascular disease and peripheral neuropathy can cause serious foot pathology.
• Smoking, hypertension, hyperlipidemia, and poor diabetic control greatly increase the risk of vascular disease.

• Associated autoimmune diseases are relatively common in children and include the following:

• Hypothyroidism affects 2-5% of children with diabetes.
• Hyperthyroidism affects 1% of children with diabetes; the condition is usually discovered at the time of diabetes diagnosis.
• Although Addison disease is uncommon, affecting fewer than 1% of children with diabetes, it is a life-threatening condition that may reduce the insulin requirement and increase the frequency of hypoglycemia. (These effects may also be the result of unrecognized hypothyroidism.)
• Celiac disease, associated with an abnormal sensitivity to gluten in wheat products, is probably a form of autoimmune disease and may occur in as many as 5% of children with IDDM.
• Necrobiosis lipoidica is probably another form of autoimmune disease. This condition is usually, but not exclusively, found in patients with IDDM. Necrobiosis lipoidica affects 1-2% of children and may be more common in children with poor diabetic control.

• Limited joint mobility, primarily affecting hands and feet, is believed to be associated with poor diabetic control.

• Originally described in approximately 30% of patients with IDDM, limited joint mobility occurs in 50% of patients older than 10 years who have had diabetes longer than 5 years. The condition restricts joint extension, making it difficult to press the hands flat against each other. The skin of patients with severe joint involvement has a thickened and waxy appearance.
• Limited joint mobility is associated with increased risks for diabetic retinopathy and nephropathy. Improved diabetes control over the past several years appears to have reduced the frequency of these additional complications by an approximate 4-fold factor. More recent patients also have markedly fewer severe joint mobility limitations.

• Apart from severe DKA or hypoglycemia, IDDM has little immediate morbidity.
• The risk of complications relates to diabetic control. With good management, patients can expect to lead full, normal, and healthy lives. Nevertheless, the average life expectancy of a child diagnosed with type 1 diabetes has been variously suggested to be reduced by 13-19 years, compared with their nondiabetic peers.

• Education is a continuing process involving the child, family, and all members of the diabetes team.