DIABETES MELLITUS

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.)

Possible mechanism for development of type 1 diabetes.

Type 2 diabetes mellitus (non–insulin-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.^[1] 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.^{[2, 3, 4]} This topic addresses only type 1 diabetes mellitus. (See Etiology and Epidemiology.)

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. (See Pathophysiology and Clinical.)^[5]

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.

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. (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.^{[6, 7]}

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is much less common than hypoglycemia but is potentially far more serious, creating a life-threatening medical emergency. 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.

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 is 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. The prevalence and severity of retinopathy increase with age and are greatest in patients whose diabetic control is poor. Prevalence rates seem to be declining, yet an estimated 80% of people with type 1 diabetes mellitus develop retinopathy.^[8]

Diabetic nephropathy and hypertension

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.^[9]

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.

Peripheral and autonomic neuropathy

The peripheral and autonomic nerves are affected in type 1 diabetes mellitus. 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.^[10] In adults, peripheral neuropathy usually occurs as a distal sensory loss.

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. 

http://emedicine.medscape.com/article/919999-overview