19.4 Diabetes
Diabetes mellitus
Diabetes mellitus is caused by a deficiency in the secretion or action of insulin. It is one of the most common chronic diseases of childhood and adolescence, and causes considerable morbidity due to acute metabolic derangements and chronic, long-term microvascular and macrovascular complications. In childhood and adolescence the most common form of diabetes is type 1 diabetes (previously known as insulin-dependent diabetes). The incidence of type 1 diabetes has doubled over the last 20 years in Australia, now at 22 cases per 100 000 population. This trend is also seen in Europe and North America. The sex ratio is equal. Diabetes is uncommon in infancy. In parallel with the overweight and obesity epidemic, there has been increased recognition of type 2 diabetes in youth in Australia and New Zealand, especially in Aboriginal and Polynesian populations. Other less common forms of diabetes result from pancreatic disease (such as cystic fibrosis-related diabetes) and a rare group of specific genetic causes of deranged insulin secretion.
Pathogenesis of type 1 diabetes
There are two major factors in the pathogenesis:
Autoimmune destruction of beta cells
Type 1 diabetes is caused by autoimmune destruction of the beta cells (insulin-producing cells) of the islets of Langerhans. T-cell infiltration of the islets and circulating autoantibodies precede the development of diabetes by months to years. This preclinical phase, when blood glucose is normal and circulating antibodies to target antigens are present, provides clues for prevention or postponement of the onset of clinical diabetes. There is an increased frequency of certain HLA types (HLA DR3/DQ2 and DR4/DQ8) in type 1 diabetes.
Environmental factors that are potential candidates in the initiation or progression of autoimmunity include the heavier childhood population with associated insulin resistance, vitamin D insufficiency, and enteroviruses. Congenital rubella is a proven, very rare, environmental trigger.
Metabolic effects of insulin
Insulin is the hormone of energy storage and anabolism. It allows glucose to enter cells and be stored as glycogen in the liver and muscle, and as triglyceride in fat. Insulin deficiency prevents glycogen and triglyceride storage and causes their breakdown, as well as that of protein. In addition, insulin deficiency promotes hepatic gluconeogenesis. The combined effect of glycogen breakdown, enhanced gluconeogenesis and failure of glucose entry into cells results in a rise in blood glucose levels. When the renal threshold is exceeded, glycosuria occurs. The osmotic effect of the glycosuria causes polyuria and eventually dehydration. Breakdown of triglyceride (lipolysis) releases free fatty acids into the circulation. In the liver these are converted to ketoacids (ketogenesis), with eventual development of ketoacidosis.
Clinical presentation
When the autoimmune process has destroyed approximately 90% of the beta-cell mass, persistent hyperglycaemia causes the initial symptoms of polyuria, polydipsia, weight loss and fatigue. In routine practice, symptoms are usually present for 1–3 weeks before the diagnosis is made; however, a child with a suspected diagnosis of diabetes should be investigated immediately. A raised postprandial blood glucose to above 9 mmol/L may be detected months before symptoms develop and before the fasting blood glucose concentration rises.
As insulin deficiency progresses, diabetic ketoacidosis develops and, if not treated, results in death. Ketoacidosis initially causes vomiting and later, rapid, deep breathing (Kussmaul respiration). The hyperventilation is a compensatory mechanism to correct metabolic acidosis by removing carbon dioxide. Chemical breakdown of acetoacetic acid in the body yields acetone, which can be detected on the patient’s breath. Abdominal pain may mimic an acute surgical abdomen. Dehydration due to continuing urinary losses caused by the osmotic diuresis may progress to shock. The acidosis, dehydration and changes in plasma osmolality cause initial irritability, then confusion, drowsiness and eventually coma. A summary of the clinical features and useful investigations at the time of presentation of type 1 diabetes is presented in Box 19.4.1.
Box 19.4.1 Type 1 diabetes: clinical features at presentation and useful investigations at diagnosis
For 2 weeks, a mother noticed that her 4-year-old son, Harry, was irritable, thirsty and wetting the bed at night, having previously been dry. After being generally less well for 24 hours he became lethargic and began vomiting. On presentation at the emergency department, he was noted to be drowsy, dehydrated and had deep sighing respirations (Kussmaul breathing). The diagnosis of diabetic ketoacidosis was confirmed when he was found to have a blood glucose level of 22 mmol/L, blood ketones were 5.2 mmol/L, serum sodium 126 mmol/L, potassium 5.2 mmol/L, bicarbonate 10 mmol/L, pH 7.15 and the base deficit 26. He was treated with intravenous isotonic fluids, intravenous potassium and intravenous insulin.
Harry was discharged 4 days later, on two injections of insulin per day, a diabetes food plan and home blood glucose testing. During the hospital admission, his family received education from the diabetes educator and dietitian, and the education programme was continued on an outpatient basis. A community diabetes educator visited Harry’s kindergarten to educate the staff about hypoglycaemia.
Differential diagnoses
The diagnosis of type 1 diabetes in childhood is not usually difficult, provided the clinician is aware that this condition can occur even in the very young. The most common misdiagnoses are to mistake:
• polyuria for urinary frequency due to urinary tract infection
• the respiratory pattern of metabolic acidosis for a respiratory tract infection or asthma
• vomiting and abdominal pain for gastroenteritis or an acute abdomen.
Children with intercurrent infections, acute asthma or hypernatraemic dehydration may have transient hyperglycaemia and glycosuria that resolves with the intercurrent illness. Only very rarely do these children develop type 1 diabetes. Islet cell autoantibodies can be tested to determine whether the child is at risk of developing type 1 diabetes.
Treatment of diabetic ketoacidosis
• emergency isotonic fluid replacement (10–20 mL per kg per h), if shock is present
• correction of dehydration slowly over 48 hours, using normal (isotonic or 0.9%) saline
• replacement of electrolyte losses and slow correction of acidosis: supplemental potassium of 40–60 mmol/L in intravenous fluids is required to maintain normal serum potassium levels after commencing insulin therapy
• correction of insulin deficiency with an infusion of soluble insulin.
Treatment should be undertaken in a centre equipped with paediatric intensive care facilities; the child may need to be transported there by an expert retrieval team. Frequent biochemical monitoring of the blood glucose, electrolytes and blood gases is required. The initial rate of insulin infusion is 0.1 unit per kg per h, and should be adjusted to produce a slow fall in the blood glucose level. Rapid reductions in the blood glucose or serum sodium concentration alter the plasma osmolality quickly and may increase the risks of the rare but life-threatening complication of cerebral oedema. Cerebral oedema is the commonest cause of death in children with diabetic ketoacidosis.
Stabilization of newly diagnosed type 1 diabetes
When ketones clear, subcutaneous insulin is begun with regular food intake. Most children are stabilized on two to four daily injections of ultra-short- and intermediate- or long-acting insulins. Within days to weeks of the introduction of insulin, some recovery of the remaining viable beta cells may occur. During this period of partial remission (also known as the ‘honeymoon’ phase), insulin requirements fall. This phase may last for weeks or months but, as the underlying autoimmune destruction of beta cells is still in progress, insulin requirements eventually rise permanently. The process of islet destruction may continue for years, providing a potential window of opportunity to increase viable beta cells by immune modulation during the pre-clinical phase and the first years after diagnosis.
Management
Aims of management
Type 1 diabetes is a permanent disorder. The long-term aims are for the child to achieve normal physical and psychological development, to lead a fulfilling life with as little restriction on lifestyle and occupation as possible, and to minimize the risk of long-term microvascular and macrovascular complications.
Management principles
Because of the complexity of diabetes management, an interdisciplinary team is essential for adequate treatment of a child with diabetes. The team members should have expertise in both paediatric care and diabetes, and would normally include a paediatrician, diabetes nurse educator, dietitian, social worker and psychologist.
The adequacy of diabetes care to maintain good metabolic control during childhood is a crucial determinant of long-term outcomes. Good metabolic control is often difficult to achieve, especially in the age group under 5 years and in adolescents. The aim is to keep preprandial and postprandial blood glucose levels as close to normal as possible. Children are asked to measure their capillary blood glucose four or more times per day. The key influences on the blood glucose levels are:
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