Pediatric Type 1 Diabetes Mellitus: Practice Essentials …

Most pediatric patients with diabetes have type 1 diabetes mellitus (T1DM) and a lifetime dependence on exogenous insulin. Diabetes mellitus (DM) is a chronic metabolic disorder caused by an absolute or relative deficiency of insulin, an anabolic hormone. Insulin is produced by the beta cells of the islets of Langerhans located in the pancreas, and the absence, destruction, or other loss of these cells results in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]). A possible mechanism for the development of type 1 diabetes is shown in the image below. (See Etiology.)

Type 2 diabetes mellitus (noninsulin-dependent diabetes mellitus [NIDDM]) is a heterogeneous disorder. Most patients with type 2 diabetes mellitus have insulin resistance, and their beta cells lack the ability to overcome this resistance. [6] Although this form of diabetes was previously uncommon in children, in some countries, 20% or more of new patients with diabetes in childhood and adolescence have type 2 diabetes mellitus, a change associated with increased rates of obesity. Other patients may have inherited disorders of insulin release, leading to maturity onset diabetes of the young (MODY) or congenital diabetes. [7, 8, 9] This topic addresses only type 1 diabetes mellitus. (See Etiology and Epidemiology.)

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. (See Pathophysiology and Clinical.) [10]

Manage mild hypoglycemia by giving rapidly absorbed oral 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. (See Treatment.)

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 to be subnormal. Overtreatment of hypoglycemia can lead to cerebral edema and death. If coma persists, seek other causes.

Hypoglycemia was a particular concern in children younger than 4 years because the condition was thought to lead to possible intellectual impairment later in life. Persistent hyperglycemia is now believed to be more damaging.

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. (See Pathophysiology, Clinical, and Treatment.)

All children with diabetes experience episodes of hyperglycemia, but persistent hyperglycemia in very young children (age < 4 y) may lead to later intellectual impairment. [11, 12]

Diabetic ketoacidosis (DKA) is much less common than hypoglycemia but is potentially far more serious, creating a life-threatening medical emergency. [13] Ketosis usually does not occur when insulin is present. In the absence of insulin, however, severe hyperglycemia, dehydration, and ketone production contribute to the development of DKA. The most serious complication of DKA is the development of cerebral edema, which increases the risk of death and long-term morbidity. Very young children at the time of first diagnosis are most likely to develop cerebral edema.

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. DKA may manifest as respiratory distress.

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 is more disfiguring.

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. The prevalence and severity of retinopathy increase with age and are greatest in patients whose diabetic control is poor. [14] Prevalence rates seem to be declining, yet an estimated 80% of people with type 1 diabetes mellitus develop retinopathy. [15]

The exact mechanism of diabetic nephropathy is unknown. Peak incidence is in postadolescents, 10-15 years after diagnosis, and it may occur in as many as 30% of people with type 1 diabetes mellitus. [16]

In a patient with nephropathy, the albumin excretion rate (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. Having diabetic nephropathy also increases the risk of significant diabetic retinopathy.

Progression may be delayed or halted by improved diabetes control, administration of angiotensin-converting enzyme inhibitors (ACE inhibitors), and 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.

The peripheral and autonomic nerves are affected in type 1 diabetes mellitus. [17] Hyperglycemic effects on axons and microvascular changes in endoneural capillaries are amongst the proposed mechanisms. (In adults, peripheral neuropathy usually occurs as a distal sensory loss.)

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. [18] In a study by 253 patients with type 1 diabetes (mean age at baseline 14.4 y), Cho et al reported that the prevalence of cardiac autonomic dysfunction increases in association with higher body mass index and central adiposity. [19]

Gastroparesis is another complication, and it which may be caused by autonomic dysfunction. Gastric emptying is significantly delayed, leading to problems of bloating and unpredictable excursions of blood glucose levels.

Although this complication is not seen in pediatric patients, it is a significant cause of morbidity and premature mortality in adults with diabetes. People with type 1 diabetes mellitus have twice the risk of fatal myocardial infarction (MI) and stroke that people unaffected with diabetes do; in women, the MI risk is 4 times greater. People with type 1 diabetes mellitus 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. Smoking, in particular, may increase the risk of myocardial infarction by a factor of 10.

Hypothyroidism affects 2-5% of children with diabetes. [20] Hyperthyroidism affects 1% of children with diabetes; the condition is usually discovered at the time of diabetes diagnosis.

Although Addison disease is uncommon, affecting less than 1% of children with diabetes, it is a life-threatening condition that is easily missed. Addison disease 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 type 1 diabetes mellitus. [21]

Necrobiosis lipoidica is probably another form of autoimmune disease. This condition is usually, but not exclusively, found in patients with type 1 diabetes. Necrobiosis lipoidica affects 1-2% of children and may be more common in children with poor diabetic control.

Limited joint mobility (primarily affecting the hands and feet) is believed to be associated with poor diabetic control. [22]

Originally described in approximately 30% of patients with type 1 diabetes mellitus, limited joint mobility occurs in 50% of patients older than age 10 years who have had diabetes for 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 a factor of approximately 4. Patients have also markedly fewer severe joint mobility limitations.

More:
Pediatric Type 1 Diabetes Mellitus: Practice Essentials ...