Molecular mimicry probably occurs between an environmental trigger and an antigen on the surface of β-cells of the pancreas. Triggers which may contribute are enteroviral infections, accounting for the more frequent presentation in spring and autumn, and diet, possibly cow’s milk proteins (Fig. 25.1) and overnutrition. In genetically predisposed individuals, this results in an autoimmune process which damages the pancreatic β-cells and leads to increasing insulin deficiency. Markers of β-cell destruction include islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD), the islet cells and insulin. There is an association with other autoimmune disorders such as hypothyroidism, Addison disease, coeliac disease and rheumatoid arthritis in the patient or family history.

Figure 25.1 Stages in the development of diabetes.

Clinical features

There are two peaks of presentation of type 1 diabetes, preschool and teenagers. It is also commoner to present in spring and autumn months. In contrast to adults, children usually present with only a few weeks of polyuria, excessive thirst (polydipsia) and weight loss; young children may also develop secondary nocturnal enuresis. Most children are diagnosed at this early stage of the illness (Box 25.2). Advanced diabetic ketoacidosis has become an uncommon presentation (<10% in some areas of the UK), but requires urgent recognition and treatment. Diabetic ketoacidosis may be misdiagnosed if the hyperventilation is mistaken for pneumonia or the abdominal pain for appendicitis or constipation.

Box 25.2 Symptoms and signs of diabetes

Early

• Most common – the ‘classical triad’:

• Excessive drinking (polydipsia)

• Polyuria

• Weight loss

• Less common:

• Enuresis (secondary)

• Skin sepsis

• Candida and other infections

Late – diabetic ketoacidosis

• Smell of acetone on breath

• Vomiting

• Dehydration

• Abdominal pain

• Hyperventilation due to acidosis (Kussmaul breathing)

• Hypovolaemic shock

• Drowsiness

• Coma and death.

Diagnosis

The diagnosis is usually confirmed in a symptomatic child by finding a markedly raised random blood glucose (>11.1 mmol/L by the current WHO definition), glycosuria and ketonuria. Where there is any doubt, a fasting blood glucose (>7 mmol/L) or a raised glycosylated haemoglobin (HbA_1c) are helpful. A diagnostic glucose tolerance test is rarely required in children.

Type 2 diabetes should be suspected if there is a family history, in children from the Indian subcontinent and in severely obese children with signs of insulin resistance (acanthosis nigricans – velvety dark skin on the neck or armpits (Fig. 25.2), skin tags or the polycystic ovary phenotype in teenage girls).

Figure 25.2 Acanthosis nigricans in axilla. A sign of insulin resistance.

Initial management of type 1 diabetes

As type 1 diabetes in childhood is uncommon (1–2 children per large secondary school), much of the initial and routine care is delivered by specialist teams (Box 25.3).

Box 25.3 The diabetes team

• Consultant paediatrician(s) with a special interest in diabetes

• Paediatric diabetes specialist nurse(s)

• Paediatric dietician

• Clinical psychologist

• Social worker

• Adult diabetologist for joint adolescent clinics

• Parent/patient support groups.

The initial management will depend on the child’s clinical condition. Those in advanced diabetic ketoacidosis require urgent hospital admission and treatment (see below). Most newly presenting children are alert and able to eat and drink and can be managed with subcutaneous insulin alone. Intravenous fluid is required if the child is vomiting or dehydrated. In most centres with sufficient resources, children newly presenting with diabetes who do not require intravenous therapy are not admitted to hospital but are managed entirely at home.

An intensive educational programme is needed for the parents and child, which covers:

• A basic understanding of the pathophysiology of diabetes

• Injection of insulin: technique and sites

• Diet: reduced refined carbohydrate; healthy diet with no more than 30% fat intake; ‘carbohydrate counting’, estimating the amount of carbohydrate in food to allow calculation of the insulin required for each meal or snack

• Adjustments of diet and insulin for exercise

• ‘Sick-day rules’ during illness to prevent ketoacidosis

• Blood glucose (finger prick) monitoring and blood ketones when unwell

• The recognition and staged treatment of hypoglycaemia

• Where to get advice 24 hours a day

• The help available from voluntary groups, e.g. local groups or ‘Diabetes UK’

• The psychological impact of a lifelong condition with potentially serious short- and long-term complications.

A considerable period of time needs to be spent with the family to provide this information and psychological support. The information provided for the child must be appropriate for age, and updated regularly. The specialist nurse should liaise with the school (teachers, those who prepare school meals, physical education teachers) and the primary care team.

Insulin

Insulin is made chemically identical to human insulin by recombinant DNA technology or by chemical modification of pork insulin. All insulin that is used in the UK in children is human and in concentrations of 100 U/ml (U-100). The types of insulin include:

• Human insulin analogues. Rapid-acting insulin analogues, e.g. insulin lispro, insulin glulisine or insulin aspart (trade names Humalog, Apidra and NovoRapid, respectively) – with a much faster onset and shorter duration of action than soluble regular insulin. There are also very long-acting insulin analogues, e.g. insulin detemir (Levemir) or glargine (Lantus)

• ‘Short-acting’ soluble human regular insulin. Onset of action (30–60 min), peak 2–4 h, duration up to 8 h. Given 15–30 min before meals. Trade named examples are Actrapid and Humulin S

• Intermediate-acting insulin. Onset 1–2 h, peak 4–12 h. Isophane insulin is insulin with protamine, e.g. Insulatard and Humulin I

• Predetermined preparations of mixed short- and intermediate-acting insulins with 25% or 30% rapid-acting components.

Insulin can be given by continuous infusion of rapid-acting insulin from a pump or by injections using a variety of syringe and needle sizes, pen-like devices with insulin-containing cartridges, and jet injectors that inject insulin needle-free as a fine stream into the subcutaneous tissue.

Insulin may be injected into the subcutaneous tissue of the upper arm, the anterior and lateral aspects of the thigh, the buttocks and the abdomen. Rotation of the injection sites is essential to prevent lipohypertrophy or, more rarely, lipoatrophy. The skin should be pinched up and the insulin injected at a 45° angle. Using a long needle or an injection technique that is ‘too vertical’ causes a painful, bruised intramuscular injection. Shallow intradermal injections can also cause scarring and should be avoided.

Most children are started on an insulin pump or a 3–4 times/day injection regimen (‘basal-bolus’) with short-acting insulin (e.g. Lispro, Glulisine or Insulin Aspart) being given (bolus) before each meal and snack plus long-acting insulin (e.g. Glargine or Detemir) in the late evening and/or before breakfast to provide insulin background (basal). These treatments both allow greater flexibility by relating the insulin more closely to food intake and exercise (Fig. 25.3). Patients and families are also taught how to correct any sugar above 10 mmol/L between usual meal times by extra short-acting insulin injections. However, the input required by the teams to start these intensive regimens is high, as is the need for a supportive school environment, and some patients and families still rely on twice-daily treatment with premixed insulin.

Figure 25.3 Basal-bolus insulin regimen and continuous pump insulin regimen, showing the basal levels of insulin programmed into the pump (blue bars) and the bolus insulin (red pulses) given before each meal/snack according to carbohydrate intake.

Shortly after presentation, when some pancreatic function is preserved, insulin requirements often become minimal, the so-called ‘honeymoon period’. Requirements subsequently increase to 0.5–1 U/kg or even up to 2 U/kg per day during puberty.

Summary

The diet and insulin regimen need to be matched (Fig. 25.4). The aim is to optimise metabolic control while maintaining normal growth. A healthy diet is recommended, with a high complex carbohydrate and relatively low fat content (<30% of total calories). The diet should be high in fibre, which will provide a sustained release of glucose, rather than refined carbohydrate, which causes rapid swings in glucose levels. ‘Carbohydrate counting’ allows patients to calculate their likely insulin requirements once their food choice for a meal is known, and taking into account their pre-meal sugar level and post-meal exercise pattern. Learning this balancing act requires a lot of educational input followed by refinement in the light of experience.